WO2010080826A1 - Compositions and methods for treating disorders associated with overweight animals - Google Patents

Compositions and methods for treating disorders associated with overweight animals Download PDF

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Publication number
WO2010080826A1
WO2010080826A1 PCT/US2010/020249 US2010020249W WO2010080826A1 WO 2010080826 A1 WO2010080826 A1 WO 2010080826A1 US 2010020249 W US2010020249 W US 2010020249W WO 2010080826 A1 WO2010080826 A1 WO 2010080826A1
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Prior art keywords
protein
similar
mrna
predicted
cfa
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PCT/US2010/020249
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French (fr)
Inventor
Ryan Michael Yamka
Sukhaswami Malladi
Xiangming Gao
Samer Al-Murrani
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Hill's Pet Nutrition, Inc.
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Priority claimed from PCT/US2009/051188 external-priority patent/WO2010009478A2/en
Application filed by Hill's Pet Nutrition, Inc. filed Critical Hill's Pet Nutrition, Inc.
Publication of WO2010080826A1 publication Critical patent/WO2010080826A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/40Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/142Amino acids; Derivatives thereof
    • A23K20/147Polymeric derivatives, e.g. peptides or proteins
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/158Fatty acids; Fats; Products containing oils or fats
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/163Sugars; Polysaccharides

Definitions

  • the invention encompasses compositions and methods for treating disorders and diseases associated with obesity.
  • the application also encompasses genes differentially expressed in animals and particularly to genes differentially expressed in obese animals compared Io lean animals.
  • the inv ention also encompasses compositions and methods for modulating the amount of fat in animals with targeted nutrition that is designed to affect, among others, key genes involved in fat metabolism.
  • the invention further identifies bioacthe dietary components that individually or together can affect the expression and activity of key genes involved in fat metabolism.
  • RNA-arbitrarily primed PCR RAP-PCR
  • RDA Representational Difference Analysis
  • mass spectrometry Reverse Phase protein array and arrays.
  • genes, proteins, and their fragments would be useful for formulating a prognosis that an animal is likely to become fat, developing a diagnosis that an animal is fat, screening substances Io determine if lhey are likely to be useful for modulating the amount of adipose tissue on an animal, and using such substances to modulate the amount of adipose tissue on an animal.
  • Overweight animals can be defined as those animals having an excess of body adipose tissue.
  • animals such as humans, canines, and felines weighing more than 15% of (heir ideal body weight are considered fat.
  • the most common cause of an animal being fat is an over consumption of food tliat results in an excess intake of calories.
  • lifestyle, health, eating habits, breed, spaying, and neutering e.g., lifestyle, health, eating habits, breed, spaying, and neutering.
  • the incidence of animals becoming overweight generally increases with age due to a general decrease in metabolic rate and in physical activity. Surv eys estimate that 25% of dogs in the United States that visit veterinary clinics are fat to the point of being obese.
  • dntgs such as phente ⁇ nine, fenfluramine, sibutramine. orlistat, and phenylpropanolamine.
  • dntgs such as phente ⁇ nine, fenfluramine, sibutramine. orlistat, and phenylpropanolamine.
  • side effects occur with these drugs.
  • fenfluramine and phentermine for the treatment of human obesity can result in cardiac valve damage in humans.
  • Sibutramine can increase blood pressure and orlistai may have unpleasant gastrointestinal side effects.
  • the imention encompasses compositions and methods useful in treating disorders in companion animals iu need thereof.
  • the invention encompasses a canine pet food composition
  • a canine pet food composition comprising an effective amount of one or more ingredients that interfere with the expression of one or more genes differential Iy expressed in overweight animals compared to lean animals, wherein said one or more ingredients that interfere with the expression of one or more genes comprise 26 wt. % to 35 wi. % of crude protein on a dry matter basis, 7.5 wt. % to 8.5 wt. % of crude fat on a dry matter basis. 20 wt. % to 30 wt. % of total dietary fiber on a dry matter basis, and 10 wt. % to 20 wt. % of crude fiber on a dry 1 matter basis.
  • the invention encompasses a feline pet food composition
  • a feline pet food composition comprising an effective amount of one or more ingredients that interfere with the expression of one or more genes differentially expressed in overweight animals compared to lean animals, wherein said one or more ingredients that interfere with the expression of one or more genes comprise: 30 wt. % to 37 wi. % of crude protein on a dry matter basis. 7,5 wt. % to 9 w t. % of crude fat on a dry matter basis, 30 wt. % to 35 wt. % of total dietary fiber on a dry matter basis, and 20 wi. % to 25 wt. % of crude fiber on a dry matter basis.
  • Another embodiment encompasses a method of treating or preventing insulin resistance in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing pancreatitis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing hypothyroidism in a companion animal in need thereof, for example, a canine, or feline, w ith a composition of the invention.
  • Another embodiment encompasses a method of treating or presenting osteoarthritis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing dyslipidemia in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or presenting hypertension in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing ocular disorders in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing altered kidney function in a companion animal in need thereof, for example, a canine or feline, with a composition of ihe invention.
  • Anoiher embodiment encompasses a method of treating or preventing respiratory' in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing artherosclerosis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or presenting diabetes mellitus in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing urinary tract disease in a companion animal in need thereof, for exajtr ⁇ ie, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or presenting hepatic lipidosis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Anoiher embodiment encompasses a method of treating or preventing hepatic dyslipidemia in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or presenting hepatic lipidosis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing neoplasia in a companion animal in need thereof, for example, a canine or feline, with a composition of the inv ention.
  • Another embodiment encompasses a method of treating or presenting oral/dental disease m a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing dermalopathy in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing lameness in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Anoiher embodiment encompasses a method of treating or preventing hyperlipidemia in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or preventing glucose metabolism disorders in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment encompasses a method of treating or presenting coronary disease in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
  • Another embodiment of the invention encompasses one or more genes or gene segments that are differentially expressed in overweight animals compared to lean animals.
  • Another embodiment of the invention encompasses combinations of two or more polynucleotides or polypeptides that are differentially expressed in overweight animals compared to lean animals.
  • Another embodiment of the invention encompasses compositions of two or more polynucleotide or polypeptide probes suitable for detecting the expression of genes differentially expressed in overweight animals compared to lean animals and devices such as substrate arrays containing the probes.
  • Another embodiment of the invention encompasses methods and compositions for detecting the differential expression of one or more genes differentially expressed in overweight animals compared to lean animals in a sample.
  • Another embodiment of the invention encompasses methods for measuring the effect of a test substance on the expression profile of one or more genes differentially expressed in overweight animals compared to lean animals as a method for screening a test substance to determine if it is likely to be useful for modulating the amount of adipose tissue on an animal.
  • Another embodiment of the invention encompasses methods for formulating a prognosis that an animal is likely to become overweight or developing a diagnosis that an animal is fat.
  • Another embodiment of the invention encompasses methods and compositions for modulating tibe expression of one or more genes differentially expressed in overweight animals compared Io lean animals or for modulating the amount of adipose tissue on an animal.
  • One or more of these embodiments are achieved using novel combinations of 433 polynucleotide probes representing genes and gene segments that are differentially expressed in the adipose tissue of overweight animals compared to the adipose tissue of lean animals (Table 1 ).
  • one or more of these embodiments are achieved using novel combinations of 1703 polynucleotide piobes representing genes and gene segments that are differentially expressed in lymphocytes taken from ov erweight animals compared to lymphocytes taken from lean animals ⁇ Table 2).
  • polynucleotide probes representing the genes and gene segments that are differentially expressed in overweight and lean dogs and are considered io be key genes for fatty acid metabolism (Table 3).
  • the polynucleotides are used to produce compositions, probes, devices based on the probes, and methods for determining the status of polynucleotides differentially expressed in overv, eight animals compared to lean animals useful for achieving the above-identified objects, e.g., proguosing and diagnosing conditions relating to animal adipose tissue and for screening substances to determine if they are likely to be useful for modulating the amount of adipose tissue on an animal. Such substances, once identified, may be used to modulate the amount of adipose tissue on an animal.
  • Various kits comprising combinations of probes, devices utilizing the probes, and substances are also provided.
  • Ii is also an embodiment of tin ' s invention to encompass methods to modulate the amount of adipose tissue in an animal in vivo by administration of composition of the invention that is shown to modulate the expression of genes involved in fat metabolism.
  • biomarkers related to obesity include, but are not limited to, glucose, insulin. GLP-I, IGF-L cholesterol, triglycerides, LUL, chylomicrons, alkaline phosphatase, type-2 cartilage synthesis, leptin, ghrelin, and combinations thereof.
  • FIGURE 1 shows lhe result for weight loss of dogs fed the formula of the present invention as compared to a control weight loss formula.
  • Figure 2 shows the shift in gene profile in dogs fed the formula of (he present invention as compared to lean dogs, obese
  • animal means a human or other animal, including avian, bovine, canine, equine, feline, hicrine, murine, ovine, and porcine animals, that has adipose tissue.
  • the animals that are compared are animals of the same species and possibly of the same race or breed. Io preferred embodiments, the animal is a canine or feline, most preferably a canine.
  • the le ⁇ n "antibody” means any immunoglobulin thai binds to a specific amigen. including IgG, IgM IgA. IgD, and IgE antibodies.
  • the term includes polyclonal, monoclonal, monovalent, humanized, heteroconjugate, antibody compositions with polyepitopic specificity, chimeric, bispecific antibodies, diabodies, single-chain antibodies, and antibody fragments such as Fab, Fab " . F(ab ' );. and Fv, or other amigen-binding fragments.
  • the term "array” means an ordered arrangement of at least two probes on a substrate. At least one of the probes is a control or standard and at least one of the probes is a diagnostic probe. The arrangement of from two or more probes (there are arrays, chips and other platforms now that go over 40,000) on a substrate assures that the si/e and signal intensity of each labeled complex formed between a probe and a sample polynucleotide or polypeptide is individually distinguishable.
  • the term "body condition score” (BCS) means a method for body- composition analysis based upon an animal's body si/e and shape. Sev eral methods are known to skilled artisans * e.g.. methods disclosed in US. Patent No. 6,691,639 and in the reference entitled “Small Animal Clinical Nutrition", 4* Edition, in Chapter 13 (ISBN 0-945.S37-05-4).
  • Body Mass Index means an animal's weight (in kilograms) divided by its height (in meters) squared
  • DEXA body composition analysis dual-energy X-ray absorptiometry.
  • the term "differential expression” or “differentially expressed ' ' means increased or upregulaled gene expression or means decreased or dowmegulated gene expression as detected by the absence, presence, or at least a 1.3-fold change in the amount of transcribed messenger RNA or translated protein in a sample.
  • the term k 'faf as applied to an animal means any animal that is determined to have no excess amount of body adipose tissue or an animal that is prone to developing an excess amount of body adipose tissue using techniques and methods known to health care providers and other skilled artisans.
  • an animal is prone to becoming overweight if the animal has an inclination or a higher likelihood of developing excess adipose tissue when compared to an average animal in ihe general population.
  • an animal is considered overweight if (1 ) the animal has a BMl of 25 or more ⁇ a number considered to include "overweight” and "obese” in some methods of characterizing animal conditions).
  • the animal ' s weight is 15Ho or mote than its "ideal" body weight as defined by health care professionals or related skilled artisans, ⁇ 3) an animal's percent body fat is 2?% or more as determined by DEXA, or (4) an animal has a body condition score of more than 3 as determined by skilled artisans using the method disclosed in '"Small Animal Clinical Nutrition.”, 4 ltl Edition, in Chapter 13 (fSBN 0-945837-05-4) or its equivalent using other BCS methods.
  • fat-associated genes means all or a subset of the genes identified in tables I and 2. particularly the geaes represented by the 433 probe sequences that are differentially expressed between adipose tissue taken from overweight animals and adipose tissue taken from lean animals as well as the genes represented by the 1703 probe sequences that are differentially expressed between the lymphocytes iaken from overweight animals and the lymphocytes taken from lean animals.
  • the term "key genes” means all or a subset of genes identified in table 3
  • the term "fold" when used as a measure of differential gene expression means an amount of gene expression in an animal that is a multiple or a fraction of gene expression compared to the amount of gene expression in a comparison animal, e.g.. a overweight animals compared to a lean animal. For example, a gene thai is expressed empe times as much in the animal as in the comparison animal lias a 3 fold differential gene expression and the gene is said to be up-regulated. On the other hand a gene that is expressed one-third as much in the animal as in the comparison animal also has a 3 fold differential gene expression and is said to be dow n-reguhued.
  • fragment means ( I ) an oligonucleotide or polynucleotide sequence that is a portion of a complete sequence and that has die same or similar activity for a particular use as the complete polynucleotide sequence or (2) a peptide or polypeptide sequence that is a portion of a complete sequence and that has the same or similar activ ity for a particular use as the complete polypeptide sequence.
  • Such fragments can comprise any number of nucleotides or amino acids deemed suitable for a particular use.
  • oligonucleotide or polynucleotide fragments contain at least 10, 50, 100. or 1000 nucleotides and polypeptide fragments contain at least 4. 10, 20, or 50 consecutive amino acids from the complete sequence.
  • the term encompasses polynucleotides and polypeptides variants or " the fragments.
  • the term “gene” or “genes” means a complete or partial segment of DNA invoked in producing a polypeptide, including regions preceding and following the coding region (leader and trailer) and intervening sequences (introm) between individual coding segments (exons). The term encompasses any DKA sequence that hybridizes to the complement of gene coding sequences.
  • the term “genes differentially expressed in overweight animals” means genes from which the amount of inRNA expressed or die amount of gene product translated from the mRNA is detect ⁇ bly different, either more or less, in tissue from overweight animals as compared to lean animals
  • the term "homoiog” means ( t) a polynucleotide, including polynucleotides from the same or different animal species, having greater than 30%. 50%. 70%, or 90% sequence similarity to a polynucleotide identified in tables 1. 2. 3 and 5 and having the same or substantially the same properties and performing the same or substantially the same function as the complete polynucleotide, or having the capability of specifically hybridizing to a polynucleotide identified in tables 1. 2. 3 and 5 under stringent conditions or (2) a polypeptide, including polypeptides from the same or different atu ' mal species, having greater than 30 1 Jo, 50% . 70%.
  • the le ⁇ "hybridization complex” means a complex thai is formed between sample polynucleotides when the purines of one polynucleotide hydrogen bond with the pyrimidines of the complementary polynucleotide, e.g.. 5 " -A-G-T-C- -V base pairs with 3 ' -T-C-A-G-S * .
  • the degree of c ⁇ mplementarily and the use of nucleotide analogs affect the efficiency and stringency of hybridization reactions.
  • conjunction means that a drug, food, or other substance is administered to an animal (1 ) together in a composition, particularly food composition, or (2) separately at the satne or different frequency using the same or different administration routes at the same time or periodically.
  • Periodically means that the substance is administered on a dosage schedule acceptable for a specific substance
  • the same lime generally means that die substance (food or drug) is administered at the same time or within 72 hours of each other.
  • '"In conjunction specifically includes administration schemes wherein substances such as drugs are administered for a prescribed period and compositions of the present invention are administered indefinitely.
  • lean as applied to an animal means any animal that is determined not to be overweight using techniques and methods known to health care providers and other skilled artisans. Generally, without limiting the definition, an animal is considered lean if ( 1) the animal has a BMl of less than 25 or (2) the animal ' s weight is less than 15% more than its "ideal" body weight as defined by health care professionals or related skilled artisans, (3) an animal's percent body fat is less than 27% as determined by DEXA, or (4) an animal lias a body condition scoie of 3 or less as determined by skilled artisans using the method disclosed in "Small Animal Clinical Nutrition". 4' 1 ' Edition, in Chapter 13 ⁇ ISBN 0-945837-05- 4) or it equivalent using other BCS methods.
  • modulating the amount of adipose tissue on an animal means causing the animal to lose adipose tissue, causing the animal to gain adipose tissue, or causing the animal to maintain the amount of adipose tissue on the animal if the animal is prone to gaining or losing adipose tissue.
  • U adipose tissue on an animal encompasses preventing a lean animal from becoming overweight and treating a overweight animal to reduce the amount of adipose tissue on the animal, as well as treating a lean animal to add adipose tissue in appropriate circumstances, e.g., when treating a lean animal that is determined by skilled artisans to be so underweight that the addition of adipose tissue is desirable.
  • Conventional methods may be used to assess the amount of adipose tissue on an ammal, as well as to determine the animal ' s lean muscle mass and /or bone mineral content, information which may be of relevance in such an assessment.
  • polynucleotide or "oligonucleotide” means a polymer of nucleotides
  • the term encompasses DNA and RNA (including c ⁇ N'A and mRNA) molecules, either single or double stranded and. if single stranded, its complementary sequence in either linear or circular form.
  • the term also encompasses fragments, variants, homologs, and alleles, as appropriate for the sequences that have the same or substantially the same properties and perform the same or substantially the same function as die original sequence.
  • the sequences may be fully complementary (no mismatches) when aligned or may have up to a 30% sequence mismatch.
  • the chain contains from 50 to 10,000 nucleotides, more preferably from 150 to 3,500 nucleotides.
  • the chain contains from 2 to 100 nucleotides, more preferably from 6 to 30 nucleotides.
  • the exact si/e of a polynucleotide or oligonucleotide will depend on various factors and on the particular application and use of the polynucleotide or oligonucleotide.
  • the term includes nucleotide polymers that are synthesized and that are isolated and purified from natural sources.
  • polynucleotide is inclusive of "oligonucleotide.”
  • polypeptide means a polymer of amino acids.
  • the term encompasses naturally occurring and non-naturally occurring (synthetic) polymers and polymers in which artificial chemical mimetics are substituted for one or more amino acids.
  • the term also encompasses fragments,, valiants, and homologs that have the same or substantially the same properties and perform the same or substantially the same function as the original sequence.
  • the term encompass polymers of any length, preferably polymers containing from 2 to 1000 amino acids, more preferably from 5 to 5(M ) amino acids.
  • the term includes amino acid polymers thai are synthesized and tliat are isolated and purified from natural sources.
  • probe means (1 ) an oligonucleotide or polynucleotide, either RN ⁇ or DNA. whether occurring naturally as in a purified restriction enzyme digest or produced synthetically, that is capable of annealing with or specifically hybridizing to a polynucleotide with sequences complementary to the probe or (2) a peptide or polypeptide capable of specifically binding a particular protein or protein fragment to the substantial exclusion of other proteins or protein fragments.
  • Au oligonucleotide or polynucleotide probe may be either single or double stranded. The exact length of the probe will depend upon many factors, including temperature, source, and use.
  • an oligonucleotide probe typically contains U ) to 100, 15 to 50. or 15 to 25 nucleotides.
  • a polynucleotide probe contains 100-1000, 300-600, nucleotides, preferably 300 nucleotides.
  • the probes herein are selected to be "substantia Hy" complementary to different strands of a particular target sequence. This means that the probes must be sufficiently complementary to specifically hybridi/e or anneal with their respective target sequences under a set of predetermined conditions. Therefore, the probe sequence need not reflect the exact complementary sequence of the target.
  • a noncomplementary nucleotide fragment may be attached to the 5 " or 3 ' end of the probe, with the remainder of the probe sequence being complementary to the target sequence.
  • nonconiplementary bases or longer sequences can be interspersed into the probe provided that the probe sequence has sufficient complementarity with the sequence of the target polynucleotide to specifically anneal to the target polynucleotide.
  • a peptide or polypeptide probe may be any molecule to which the protein or peptide specifically binds, including DNA (for DNA binding proteins), antibodies, cell membrane receptors, peptides, cofactors. lectins, sugars, polysaccharides, cells, ceil membranes, organelles and organella! membranes.
  • sample means any animal tissue or fluid containing, e.g., polynucleotides, polypeptides, antibodies, metabolites, and the like, including cells and other tissue containing DKA and RNA. Examples include adipose, blood, cartilage, connective, epithelial, lymphoid, muscle, nervous, sputum, and the like.
  • a sample may be solid or liquid and may be DNA, RNA, cDNA, bodily fluids such as blood or urine, ceils, cell preparations or soluble fractions or media aliq ⁇ ots thereof, chromosomes, organelles, and the like.
  • single package means that the components of a kii are physically associated in or with one oi more containers and considered a unit for manufacture, distribution, sale, or use.
  • Containers include, but are not limited to, bags, boxes, bottles, shrink wrap packages, stapled or otherwise affixed components, or combinations thereof.
  • a single package may be containers of individual food compositions physically associated such that they are considered a unit for manufacture, distribution, sale, or use.
  • the term "useful variations" means (1 ) for a polynucleotide, the complements of the polynucleotide; the homologs of the polynucleotide and its complements; the variants of the polynucleotide, its complements, and its homologs: and the fragments of the polynucleotide, its complements, its homologs, and its variants and (2) for a polypeptide, the homologs of the polypeptide; the variants of the polypeptide and its homologs; and the fragments of the polynucleotide, its homologs, and its variants.
  • kits are associated by directions on one or more physical or virtual kit components instructing the user how to obtain the other components, e.g., in a bag containing one component and directions instructing the user to go to a website, contact a recorded message, view a visual message, or contact a caregiver or instructor to obtain instructions on how to use the kit.
  • standard means ⁇ 1 ) a control sample that contains tissue from a lean animal if a overweight animal is being tested or tissue from a overweight animal if a lean animal is being tested or (2) a control sample that contains tissue from a lean or overweight lest animal that has not been exposed to a test substance being examined in the corresponding lean or overweight animal to determine if the test substance causes differential yene expression, as appropriate for the context of its use.
  • stringent conditions means (1 ) hybridization in 50% (vol/vol) fo ⁇ namide with 0.1 % bovine serum albumin. 0.1% Ficotl, 0, 1% polyvinylpyrrolidone, 50 mM sodium phosphate buffer at pH 6.5 with 750 mM NaCI, 75 mM sodium citrate at 42T. (2) hybridization in 50% formamide, 5x SSC (0.75 M NaCI. 0.075 Vl sodium citrate).
  • the term "substance” means an element, compound, molecule, or a mix hire thereof or any other material that could potentially be useful for diagnosing, prognosing. or modulating the amount of adipose tissue on animals, including any drug, chemical entity, or biologic entity.
  • siRN ⁇ means a polynucleotide that forms a double stranded RNA that reduces or inhibits expression of a gene when the siRNA is expressed in the same cell as the gene.
  • the term encompasses double stranded RNA formed by complementary strands.
  • the siRNA complementary portions that hybridi/e to form the double stranded molecule typically have substantial or complete identity.
  • siRNA contains at least 15-50 nucleotides and the double stranded siRNA contains 15-50 base pairs, preferably 20-30 nucleotides and base pairs.
  • specifically bind means a special and precise interaction between two molecules uhich is dependent upon their structure, particularly their molecular side groups.
  • the term "specifically hybridi/e” means an association between two single stranded polynucleotides of sufficiently complementary sequence to permit such hybridization under predetermined conditions generally used ui the art (sometimes termed “substantially complementary”).
  • the term may refer to hybridization of a polynucleotide probe with a substantially complementary sequence contained within a single stranded IWA or RNA molecule according to an aspect of the invention, to the substantial exclusion of hybridization of the polynucleotide probe with single stranded polynucleotides of non-complementary sequence.
  • the term “variant” means ( D a polynucleotide sequence containing any substitution, variation, modification, replacement, detelkm.
  • nucleotide sequence cotuain ⁇ ig any substitution, variation, modification, replacement, deletion, or addition of one or mote amino acids from or to a polypeptide sequence and that has the same or substantially the same properties and performs the same or substantially the same function as the original sequence
  • polypeptide sequence cotuain ⁇ ig any substitution, variation, modification, replacement, deletion, or addition of one or mote amino acids from or to a polypeptide sequence and that has the same or substantially the same properties and performs the same or substantially the same function as the original sequence.
  • SNPs single nucleotide polymorphisms
  • allelic variants includes conservative and non- conservative amino acid substitutions in polypeptides.
  • the term also encompasses chemical derivati/ation of a polynucleotide or polypeptide and substitution of nucleotides or amino acids with nucleotides or amino acids that do not occur naturally, as appropriate.
  • the present invention encompasses one or more genes or gene segments ("genes' " as defined herein) that are differentially expressed in the adipose tissue and/or lymphocytes of overweight animals compared to the adipose tissue and or lymphocytes of lean animals.
  • the im ention is based upon the discovery of diffenrenhally expressed genes thai are represented by 445 polynucleotides in the adipose tissue of overw eight animals compared to the adipose tissue of lean animals and 1767 polynucleotides in the lymphocytes taken from overweight animals compared to lymphocytes taken from lean animals.
  • the invention is further based upon the identification of 7 key genes involved in fatty acid metabolism that are diffenretially expressed between overweight and lean animals and are listed in (able 3. These key genes represent members of the pyruvate dehydrogenase kinase family, the carnitine palmitoyltransferase family and soluie carrier family 27 (fatty acid transporters) and genes associated with the elongation of long chain fatty acids, with the pyruvate dehedrogenase kinase family and the carnitine palmitoyltransferase family being the most important and in some instances rate limiting enzymes.
  • the genes were identified by comparing the expression of genes in adipose tissue and lymphocytes taken from animals diagnosed as overweight with genes in adipose tissue and lymphocytes from animals diagnosed as lean using Affymelrix GeneChiptf technology.
  • the polynucleotides are shown in " fable 1 , 2 and 3.
  • the tables contain information the ⁇ ffymetrix Probe Identification Number (herein "APlN"). the p-value. the q- ⁇ alue, fold expression (fat, lean), the top BLAST annotation of the probe in question, the Accession Number of Highest BLAST Hit, the gene symbol and finally ⁇ he gene description is given in (he last column.
  • the putative or actual gene function is determined by ( I) identifying the APfN for each gene that had 1.3 fold or greater gene expression in overweight animals compared to lean animals, (2) determining the nucleotide sequence of each such gene by inputting die APl 1 N into the publicly available Affymetrix database UmI correlates AlPN numbers with sequences, and (3) inputting the nucleotide sequence into the BLAST database provided by the National institutes of Health and determining the putative or actual gene function from the resulting sequence matches to homologous sequences in the database.
  • the polynucleotides and genes are identified by measuring differences in gene expression from adipose tissue and the lymphocytes from canines diagnosed as overweight with gene expression in adipose tissue and the lymphocytes from canines diagnosed as lean. Changes in gene expression can be determined by any method known to skilled artisans. Generally, changes in gene expression are determined b> measuring transcription (determining the amount of mRNA produced by a gene) or measuring translation (determining the amount of protein produced by a gene). The amount of RNA or protein produced by a gene can be determined using any method known to skilled artisans for quantifying polynucleotides and proteins. Generally.
  • RNA expression is determined using methods including but not limited to polymerase chain reaction (PCR) (including, without limitation, reverse transcription-PCR (RT-PCR) and quantitative real-time PCR (qPCR)), RNase protection. Northern blotting, and other hybridization methods.
  • PCR polymerase chain reaction
  • RT-PCR reverse transcription-PCR
  • qPCR quantitative real-time PCR
  • the RNA measured is typically in the form of mRNA or reverse transcribed mRNA or complimentary DNA (cDNA).
  • Protein or polypeptide expression is determined using various colormetric.
  • floureseense and spectroscopic assays and methods including but not limited to Western Blotting, ELISA, Multiple Reaction Monitoring. Reverse Phase and Antibody Arrays.
  • changes in gene expression are determined using Affymetrix Canine- 1 and Canine- 2 GeneChip ⁇ available for purchase from AlTymelrix. Inc.
  • differential gene expression in o ⁇ erweight animals compared to lean animals is determined by measuring the expression of at least one gene.
  • the expression of two or more differentially expressed genes is measured to provide a gene expression pattern or gene expression profile. More preferably, the expression of a plurality of differentially expressed genes is measured.
  • polynucleotides, genes, proteins encoded by the polynucleotides and genes, and the complements, homologs, variants, or fragments based upon the sequences are useful in a variety of prognostic and diagnostic assays relating to the amount of adipose tissue on an animal and are nseftil for screening test substances to determine if the substances are useful for modulating the amount of adipose tissue on an animal.
  • prognostic and diagnostic assays relating to the amount of adipose tissue on an animal and are nseftil for screening test substances to determine if the substances are useful for modulating the amount of adipose tissue on an animal.
  • the invention provides a combination comprising two or more polynucleotides that are differentially expressed in overweight animals compared to lean animals or two or more proteins produced by the expression of two or more polynucleotides that are differentially expressed m overweight animals compared to lean animals.
  • the combination comprises two or more polynucleotides or proteins expressed from polynucleotides selected from Tables 1 and 2 and preferably from table 3.
  • the combination comprises a plurality of polynucleotides or proteins expressed from polynucleotides identified in tables 1 and 2 and preferably from table 3, generally 10, 20. 50, H)O.
  • polynucleotides or proteins us appropriate for a particular Group and use.
  • the fragments can be of any si/e that retains the properties and function of the original polynucleotide or protein, preferably from 30"'», 6O 0 ZO. or 90% of the original.
  • the polynucleotides and proteins can be from any animal, preferably canines and felines, most preferable canines.
  • the invention pros ides a composition comprising two or more oligonucleotide or polynucleotide probes suitable for detecting the expression of genes differentially expressed in overweight animals compared to lean animals.
  • the probes comprise polynucleotides selected from tables I and 2 and preferably from table 3.
  • the probes comprise useful v ariations of such polynucleotides.
  • the probes contain a sufficient number of nucleotides to specifically hybrid i/e substantially exclusively with appropriate complementary polynucleotides.
  • the probes comprise at least 10, 35, 20, 25, or 30 nucleotides.
  • the probes contain more nucleotides and comprise at least 30. 50. 70. 90 or 100 nucleotides, or more.
  • the probes may comprise full length functional genes of the present invention.
  • the composition comprises a plurality of polynucleotide probes suitable for detecting genes differentially expressed in overweight animals compared to lean animals, generally 10, 50, 200, 500, 1000, or 2000, or more probes.
  • the polynucleotide probes are made or obtained using methods known to skilled artisans, e.g., in vitro synthesis from nucleotides, isolation and purification from natural sources, or enzymatic cleavage of the genes of the present invention.
  • the invention provides a device suitable for detecting the expression of a plurality of genes differentially expressed in overweight animals compared to lean animals.
  • the device comprises a substrate having a plurality of the oligonucleotide or polynucleotide probes of the present inv ention affixed to the substrate at known locations.
  • the device is essentially an immobilized version of the oligonucleotide or polynucleotide probes described herein. The device is useful for rapid and specific detection of genes and polynucleotides and their expression patterns and profiles.
  • probes are linked to a substrate or similar solid support and a sample containing one or more polynucleotides (e.g., a gene, a PCR product a ligase chain reaction (LCR) product, a DNA sequence that has been synthesized using amplification techniques, or a mixture thereof) is exposed to lhe probes such that the sample polynucleo ⁇ ide(s) can hybridize to the probes.
  • a sample polynucleotides e.g., a gene, a PCR product a ligase chain reaction (LCR) product, a DNA sequence that has been synthesized using amplification techniques, or a mixture thereof
  • LCR ligase chain reaction
  • hybridization may be detected by detecting bound fluorescence. If the probes are labeled, hybridization is typically detected by label quenching. If both die probe and the sample polynucieotide(s) are labeled, hybridization is typically detected by monitoring a color shift resulting from proximity of the two bound labels.
  • labeling strategies and labels are known to skilled artisans, particularly for fluorescent labels.
  • the probes are immobilized, on substrates suitable for forming an
  • the invention provides a composition comprising two or more peptide or polypeptide probes suitable for detecting the expression of genes differentially expressed in overweight animals compared io lean animals.
  • the probes comprise peptides or polypeptides that specifically bind to proteins produced by the expression of one or more polynucleotides comprising sequences selected from tables I and 2.
  • the probes comprise peptides or polypeptides that specifically bind to proteins produced by expression of one or more polynucleotides comprising sequences selected from table 3..
  • the probes comprise peptides or polypeptides ihat specifically bind to proteins produced by expression of one or more useful variations of such polypeptides.
  • the probes contain a sufficient number of amino acids to specifically bind to the appropriate polypeptides.
  • the probes comprise at least 4, 10, 20, 40, or KO amino acids.
  • the probes contain more amino acids and comprise at least 100 or more amino acids.
  • the probes may comprise full length functional proteins derh ed from the expression of full length functional genes identified by the present invention.
  • the invention provides a plurality of polypeptide probes suitable for detecting genes differentially expressed in overweight animals compared to lean animals, more preferably a collection of 10, 50, 100, 500, or 1000 or more of such probes.
  • the probes are antibodies, preferably monoclonal antibodies.
  • the polypeptide probes may be made according to conv entional methods, e.g., using the nucleotide sequence data provided for polynucleotides of the present invention and methods known in the art. Such methods include, but are not limited to, isolating polypeptide directly from cells, isolating or synthesizing DNA or RNA encoding the polypeptides and using the DNA or RNA to produce recombinant products, synthesizing the polypeptides chemically from individual amino acids, and producing polypeptide fragments by chemical cleavage of existing polypeptides.
  • the invention provides a device suitable for detecting the expression of a plurality of genes differentially expressed in overweight animals compared to lean animals.
  • the device comprises a substrate having a plurality of the peptide or polypeptide probes of the present invention affixed to the substrate at known locations.
  • the device i.s essentially an immobilized version of the peptide or polypeptide probes described herein.
  • the device is useful for the rapid and specific detection of proteins and their expression patterns.
  • probes are linked to a substrate and a sample containing one or more proteins is exposed to the probes such that the sample proteins can hybridize to the probes
  • the probes, the sample proteins, or both are labeled and detected, typically with a tluorophore or other agent known to skilled artisans.
  • the same methods and instrumentation used for reading polynucleotide microarrays is applicable to protein arrays.
  • the probes are immobilized on a substrate suitable for forming an array.
  • Methods for determining the amount or concentration of protein in a sample are known to skilled artisans. Such methods include radioimmunoassays, competim e- binding assays, Western blot analysis, and ELlSA assays.
  • methods that use antibodies polyclonal and monoclonal antibodies are suitable. Such antibodies may be immunologically specific for a protein, protein epitope, or protein fragment.
  • Some embodiments of the invention utilize antibodies for the detection and quantification of proteins produced by expression of the polynucleotides of the present invention.
  • proteins may be detected by immunoprecipitation, affinity separation.
  • Western blot analysis, protein arrays, and the like a preferred method utilizes ELISA technology wherein the antibody is immobilized on a solid support and a target protein or peptide is exposed to the immobilized antibody. Either the probe, or the target, or both, can be labeled using known methods.
  • expression patterns or profiles of a plurality of genes differentially expressed in overweight animals compared to lean animals are observed utilizing an array of probes for detecting polynucleotides or polypeptides.
  • arrays of oligonucleotide or polynucleotide probes may be utilized, whereas another embodiment may utilize arrays of antibodies or other proteins that specifically bind to the differentially expressed gene products of the present invention.
  • arrays may be commercially available or they may be custom made using methods known to skilled artisans, e.g., in-situ synthesis on a solid support or attachment of pre-synthesized probes to a solid support via micro-
  • arrays of polynucleotides or polypeptides probes are custom made to specifically detecl transcripts or proteins produced by the differentially expressed genes of the present invention.
  • arrays of polynucleotide or polypeptide probes are custom made to specifically delect transcripts or proteins produced by two or more polynucleotides or genes identified in Table 2. These probes are designed to detect genes associated with lipid and glucose metabolism pathways in animals.
  • arrays of polynucleotide or polypeptide probes are custom made to specifically detect transcripts or proteins produced by two or more polynucleotides or genes identified in Table 3. These probes are designed to detect genes that are particularly relevant to overweight animals compared to lean animals.
  • the invention provides a method for detecting the differential expression of one or more genes differentially expressed in o ⁇ erweight animals compared to lean animals in a sample.
  • the method comprises (a) hybridizing a combination comprising a plurality of polynucleotide probes that are differentially expressed in overw eight animals compared to lean animals with polynucleotides in the sample to form one or more hybridization complexes: (b) optionally, hybridizing a combination comprising a plurality of polynucleotide probes that are differentially expressed in overweight animals compared to lean animals with polynucleotides in a standard to form one or more hybridization complexes; (c) detecting the hybridization complexes from the sample and, optionally, the standard from step (b); and (d) comparing the hybridization complexes from the sample with the hybridization complexes from a standard, wherein a difference in the amount of hybridization complexes between the standard and sample indicate differential
  • me plurality of polynucleotide probes are selected from Tables 1 and 2 and preferably from table 3. These polynucleotides are used to prepare probes that hybridize with sample polynucleotides to form hybridization complexes that are detected and compared with those of the standard. In some embodiments, the sample polynucleotides are amplified prior to hybridization. In some embodiments, the probes are bound to a substrate, preferably in an array.
  • Step (b) and part of step (O are optional and are used if a relatively contemporaneous comparison of two or more test systems is to be conducted.
  • the standard used for comparison is based upon data previously obtained using the method.
  • probes are exposed to a sample to form hybridization complexes that are detected and compared with those of a standard.
  • the differences between the hybridization complexes from the sample and standard indicate differential expression of polynucleotides and therefore genes differentially expressed in overweight animals compared to lean animals in the sample.
  • probes are made to specifically detect polynucleotides or fragments thereof produced by one or more of the genes or gene fragments identified by the present invention. Methods for detecting hybridization complexes are know n to skilled artisans.
  • the method further comprises exposing the animal or sample to a test substance before hybridization. Then, the comparison is indicative of whether the test substance altered the expression of genes differentially expressed in overweight animals compared to lean animals, particularly fat- associated genes, in the sample.
  • the invention provides a method for detecting the differential expression of genes differentially expressed in overweight animals compared to lean animals in a sample.
  • the method comprises (a) reacting a combination comprising a plurality of polypeptide probes with proteins in the sample under conditions thai allow specific binding between the probes and the proteins to occur, wherein the proteins bound by the probes are differentially expressed in a overweight animal compared to a lean animal; (b) optionally, reacting a combination comprising a plurality of polypeptide probes with, proteins in a standard under conditions that allow specific binding between the probes and the proteins to occur, wherein the proteins bound by the probes are differentially expressed in a overweight animal compared to a lean animal, (c) detecting specific binding in the sample and. optional!) , the standard from step (b); and (d) comparing the specific binding in the sample with that of a standard, wherein differences between the specific binding in the standard and the sample indicate differential
  • the plurality of polypeptide probes are probes that specifically bind to proteins produced by expression of one or more polynucleotides selected from Tables 1 aad 2 and preferably from table 3 and useful variations of such polynucleotides. These polynucleotides are used to prepare probes that specifically bind to proteins that are detected and compared with those of the standard.
  • the probes are bound to a substrate, preferably in an array . fn one embodiment, the probes are antibodies.
  • Step (b) and part of step (c) are optional and are used if a relatively contemporaneous comparison of two or more test systems is to be conducted. However, in a preferred embodiment, the standard used for comparison is based upon data previously obtained using the method.
  • probes are exposed to a sample to form specific binding that is detected and compared with those of a standard.
  • the differences between the specific binding from the sample and standard indicate differential expression of proteins and therefore genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, in the sample.
  • probes are made to specifically detect proteins or fragments thereof produced by one or more of the genes or gene fragments identified by the present invention.
  • the method further comprises exposing the animal or sample to a test substance before reacting the polypeptides with the proteins. Then, the comparison is indicative of w hether the test substance altered the expression of genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, in the sample.
  • the method for detecting the expression of genes differentiall ⁇ expressed in overweight animals compared to lean animals in a sample is used to monicot an animal ' s progress when attempting to modulate the amount of adipose tissue on the animal in response to an adipose tissue modulation program.
  • the method is performed at intervals, preferably set intervals, during the modulation program and the animal's progress monitored by comparing the results of the method at tw o or more points during the modulation program.
  • 25 expression of one or more of the genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, or i» the pattern of gene expression, or the lack of any change, resulting from the comparison indicates the effectiveness of the modulation program.
  • an adipose tissue modulation program designed io reduce die amount of adipose tissue on an animal could be monitored and shown to be effective if the amount of gene expression for genes differentially expressed in overweight animals compared to lean animals, particularly fat-associaied genes, declines oser time in response to the stimulus in the program.
  • a program to increase adipose tissue in a lean or overly lean animal should increase the expression profile for such genes.
  • the modulation program can be any plan to modulate the amount of adipose tissue on the animal such as a diet, exercise, drug, or other similar program.
  • the invention provides a method for measuring the effect of a test substance on the expression profile of one or more genes differentially expressed in overweight animals compared to lean animals and a method for screening a lest substance to determine if it is likely to be useful for modulating the amount of adipose tissue on an animal.
  • the methods comprise (a) determining a first expression profile by measuring the transcription or translation products of two or more polynucleotides selected from Tables 1 and 2 and preferably from table 3 or useful variations thereof in a test system in the absence of the test substance; (b) determining a second expression profile by measuring the transcription or translation products of two or more polynucleotides selected from Tables I and 2 and preferably from table 3 or useful variations thereof in a lest system in the presence of the test substance; and (c) comparing the first expression profile to the second expression profile.
  • a change in the second expression profile compared to the first expression profile of 1.3 fold or more indicates that the test substance effects the expression of genes differentially expressed in overweight animals compared to lean animals and that the test substance is likely to be useful for modulating the amount of adipose tissue on an animal.
  • the genes differentially expressed in overweight animals compared to lean animals are key genes associated with fatty acid metabolism and the change is a 1.3 fold or more change in expression of at
  • the test .system is an in vitro test system such as a tissue culture, cell extract, or cell line.
  • the test system is an in vivo test system, i.e.. an animal such as a canine.
  • the test system is an ex vivo tissue system or an in sihco system.
  • Test substances can be any substance that may have an effect on polynucleotides or genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes.
  • Test substances include, but are not limited to. amino acids; proteins, peptides, polypeptides, nucleic acids, oligonucleotides, polynucleotides, small molecules, macromolecules, vitamins, minerals, simple sugars; complex sugars; polysaccharides; carbohydrates; medium- chain triglycerides (MCTs); triacylglycerides (TAGs); n-3 (omega-3 ) fatly acids including DIIA, EPA, ALA; n-6 (omega-6) fatty acids inciudmg LA, ⁇ -li»oleuic acid (GLA) and ARA; SA.
  • CLA conjugated linoleic acid
  • choline sources such as lecithin
  • fat-soluble vitamins including vitamin A and precursors thereof such as carotenoids ⁇ e.g., jVcarotene), vitamin D sources such as vitamin D; (ergocalciferol) and vitamin D,-, (cholecakiferol), vitamin E sources such as tocopherols ⁇ e g., ⁇ -tocopherol) and tocotrienols
  • vitamin K sources such as vitamin K] (phylloquinone) and vitamin Ko (menadione)
  • water-soluble v itamins including B vitamins such as riboflavin, niacin (including nicotinamide and nicotinic acid), pyridoxine, pantothenic acid, folic acid, biotin and cobalamin; and vitamin C (ascorbic acid); antioxidants, including some of the vitamins listed above, especially vitamins E and C; also bioflavonoids such as catechin
  • test substances are nutrients that may be added to food or consumed as a supplement.
  • examples include, but are not limited to, fatty acids such as omega-3 fatty acids (e.g.. DHA and EPA) and omega-6 fatty acids (e.g.. ARA), carnitine, methionine, vitamin C, vitamin E. and vitamin D.
  • the substances useful for affecting the expression of genes differentially expressed in overweight animals compared to lean animals may be identified using methods discloses in co-pending IiS Provisional Patent Application No. 60/657980, filed March 2, 2005, and any subsequent US or foreign patent application that claims priori iy thereto.
  • the invention encompasses a method for formulating a prognosis that an animal is likely to become overweight or developing a diagnosis that an animal is fat.
  • the method comprises determining if one or more polynucleotides selected from tables i and 2 or useful variations thereof or one or more polypeptides that specifically bind to proteins produced by expression of one or more polynucleotides selected from tables K 2 or useful variations thereof are differentially expressed in the animal compared to one or mote lean animals.
  • the animal is determined to be likely to become overweight or determined to be overweight if the comparison indicates that the polynucleotides are differentially expressed in the animal compared to the lean animals by a fold of 1.3 or more.
  • the prognosis or diagnosis is based upon the polynucleotides selected from Table 3. or useful variations of such polypeptides.
  • the expression profile for lean animals used in the comparison can be obtained from one or more lean animals contemporaneously w ' ln the expression profile for the animal being tested of from a database of lean animal expression profiles.
  • a database of expression profiles for lean animals accumulated over time is available for use as a reference.
  • the invention provides a method for manipulating the genome or the expression of the genome of an animal, particularly a non-human animal.
  • the method comprises disrupting the expression of one or more genes differentially expressed in overweight animals compared to lean animals, preferably using oligonucleotides or polynucleotides constructed using
  • Methods of manipulating the genome are known to those of skilled in the an. Such methods include the production of transgenic and knockout animals and (lie disruption of transcription or translation.
  • one or more polynucleotides selected from tables 1 and 2 or useful variations thereof are used to prepare a construct useful to disrupt or "knock out" the corresponding endogenous gene in an animal.
  • This method produces an animal having a null mutation for that gene locus, fn other embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-assoctated genes.
  • the invention also provides an animal produced using the method.
  • the genome is manipulated using ihe one or more polynucleotides selected from Table 3. or useful variations of such sequences.
  • the transgenic animals are preferably mammals, e.g., rodents such as mice and rats, but may be other mammal such as felines and canines.
  • Methods of manipulating the expression of genome are known to those of skilled in the art. Such methods include the use of antisense or siRNA molecules and using such molecules to disrupt the translation or transcription of the genome, fn one embodiment, one or more polynucleotides selected from tables I and 2 and preferably from table 3 or useful variations thereof are used to prepare antisense and similar DNA binding molecules that are useful for disrupting transcription or to prepare short ⁇ small) interfering RNAs (siRNA) useful for functionally disrupting translation. Briefly, gene expression is inhibited by anlisense molecules through binding to DMA and preventing transcription and a siRNA through RNA interference (RNAi) or post-iranscriptional gene silencing (PTGS).
  • RNAi RNA interference
  • PTGS post-iranscriptional gene silencing
  • siRNA molecules target homologous mRNA molecules for destruction by cleaving the niRNA molecule within the region spanned by the siRNA molecule. Accordingly. siRNAs capable of taigeting and cleaving a mRNA transcribed from a fat- associated gene is used to decrease or eliminate expression of one or more of such genes. In other embodiments, antisense molecules capable of binding to DNA and siRNAs capable of targeting and cleaving mRNA transcribed from one or more
  • 29 polynucleotides or genes selected from tables t and 2 and preferably from table 3 or useful variations thereof.
  • the invention provides a composition suitable for manipulating the genome of an animal.
  • the composition comprises one or more substances that interfere with the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat- associated genes.
  • substances comprise oligonucleotides or polynucleotides that bind to one or more of the genes or their transcription products and interferes with their replication, transcription, or translation, most preferably oligonucleotides or polynucleotides constructed using polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof.
  • the substances comprise antisense molecules or siRNAs.
  • the invention encompasses a method for modulating the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, or modulating the amount of adipose tissue on an animal comprising administering to the animal a gene expression or tissue modulating amount of a composition comprising one or more of DH ⁇ , EPA. EPA and DHA, ALA, LA, ARA, SA and MA.
  • the composition comprises, in milligrams per kilogram of body weight per day (mg/kg/day).
  • DHA in amounts of from I to 30, preferably from 3 to 15: EPA in amounts of from 1 to 30, preferably from 3 to 15; EPA, DHA Combo (1.5: 1 ratio) in amounts of from 4/2 to 30/45, preferably from 9,6 to I S/12; ALA in amounts of from 10 to 100, preferably from 30 to 60; 1..A in amounts of from 30 to 600, preferably from 60 to 300: ARA in amounts of from 5 to 50, preferably from 15 to 30: SA in amounts of from 3 to 60, preferably from 6 to 30; MA in amounts of from 3 to 60, preferably from 6 to 30; and CLA (as a control) in amounts of from 6 to 120. preferably from 12 to 60.
  • the composition can be administered to the animal in any manner or form suitable for the composition.
  • the composition is administered to the animal orally in the form of a food composition or a supplement.
  • the food composition may be of any form, e.g., a nutritionally balanced food composition known in the art such as dry foods, semi-moist foods, and v ⁇ et foods for animals, particularly companion animals such as feline and canine animals.
  • Supplements include dosage forms such
  • the composition is administered in combination with one or more drugs or other substances that modulate the amount of adipose tissue on an animal.
  • the drugs or substances include, but are not limited to. substances that suppress appetite, increase metabolism, or interfere with the absorption of specific nutrients, particularly from food. Examples include, but are not limited to. orhstat (blocks fat breakdown and absorption), anorexigenics such as dexedrine (suppresses appetite), anorectics such as fenfluramine and phentermine. and sibutramine, and phenylpropanolamine.
  • the invention provides a composition suitable for modulating the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, or modulating the amount of adipose tissue on an animal.
  • the composition comprises a gene expression or tissue modulating amount of one or more of DHA. EPA, EPA and DHA, ALA. LA, ARA, SA. MA.
  • the composition comprises, in mg kg/day.
  • DHA in amounts .sufficient to administer to an animal from 1 to MK EPA in amounts sufficient to administer to an animal from t to 30; EPA DHA Combo (1.5:1 ratio) in amounts sufficient to administer to an animal from 4/2 to 30,45: ALA in amounts sufficient to administer to an animal from 10 to 100: LA in amounts sufficient to administer to an animal from 30 to 600; ARA in amounts sufficient to administer to an animal from 5 to 50; SA in amounts sufficient to administer to an animal from 3 to 60; MA in amounts sufficient to administer to an animal from 3 to 60 and CLA (as a control) i « amounts sufficient to administer to an animal from (• > to 120.
  • the substances are useful for modulating the amount of adipose tissue on an animal. .
  • the substances affect the expression of a plurality of such genes.
  • the composition further comprises one or more drugs or other substances that modulate the amount of adipose tissue on an animal.
  • the invention encompasses methods for selecting an animal for inclusion in one or more groups or subgroups.
  • the method comprises determining the expression profile of the animal for (a) polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof or (b) polypeptides each of which specifically binds to proteins produced by expression of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful v ariations thereof and assigning the animal to a group based upon the expression profile.
  • the groups can be any useful groups, preferably those involved in a research experiment, trial, clinical trial, or other similar category.
  • the groups can be groups involv ed in a research experiment or clinical trial that requires a one or more coturol groups and one or more treatment groups
  • the control group comprises lean animals and the treatment group comprises overweight animals, or v ice versa in another.
  • the expression profile for a plurality of animals can be determined and the animals assigned to the control group or treatment group based upon the results of the profile, i.e., animals with a differential expression of 1 ,3 fold or more compared to a standard are assigned to the overweight group and animals with a differential expression of 1.3 fold or less compared to a standard are assigned to the lean group.
  • the method is particularly useful for assigning animals to a clinical trial when testing potential drugs or other substances for their ability to reduce the amount of adipose tissue on the animal.
  • the invention provides a computer system suitable for manipulating data relating to one or more genes differentially expressed in ov erweight animals compared to lean animals, particularly fat-associated genes.
  • the system comprises a database containing information identifying the expression le ⁇ el of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof and/or polypeptides that specifically bind to proteins produced by the expression of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof in lean animals and/or overweight animals and a user interface to interact with the database, particularly to input, manipulate, and rev iew the information for different animals or categories or animals, e.g., lean or overweight animals.
  • the database further contains information identifying the activity level of one or more polypeptides encoded by one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof, in another, the database further comprises sequence information for one or more of the polynucleotides selected from tables I and 2 and preferably from (able 3 or useful variations thereof. In other embodiments, the database contains additional information describing the putative description of the genes in one or more animal species.
  • the computer system is any electronic device capable of containing and
  • a user e.g., a typical computer or an analytical instrument designed to facilitate using the present invention and o ⁇ tputiing the results relating to the status of an animal.
  • the invention provides a method for using a computer system or the present invention to present information identifying the expression profile of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes.
  • the method comprises comparing the expression level of two or more polynucleotides or proteins expressed from polynucleotides selected from tables 1 and 2 and preferably from table 3 form a sample to the expression profile of the polynucleotides or proteins in the computer system.
  • kits suitable for determining the differential expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat- associated genes, in a test system comprise in separate containers in a single package or in separate containers in a virtual package, as appropriate for the use and kit component, two or more probes suitable for detecting the expression of genes differentially expressed in overweight animals compared to lean animals, the probes comprising (a) polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof or ⁇ b) polypeptides that specifically bind to proteins produced by the expression of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof and at least one of (1 ) instructions for how to use the probes of the present invention: (2) reagents and equipment necessary to use the probes: (3) a composition suitable for modulating the expression of one or more genes differentially expressed in overweight animals compared to lean animals; (4) a
  • the invention encompasses canine food compositions including 26 wt. % to 35 wt. % of crude protein on a dry matter basis, 7.5 wt. % to 8.5 wt. % of crude fat on a dry matter basis, 20 wt. % to 30 ⁇ v ⁇ . % of total dietary- fiber on a dry matter basis, and IO wt. % to 20 wt. % of etude fiber on a dry matter basis.
  • the invention also encompasses feline food compositions including 30 wt. % to 3? wt. % of crude protein on a dry matter basis, 7.5 wt.
  • compositions of the invention can include an omega-3 polyunsaturated fatty acid content of at least 0.02% (or 0.05 % to 10%, or 0.1 % to 6%) by weight on a dry matter basis.
  • the oniega-3 polyunsaturated fatty acid is DHA.
  • the omega-3 polyunsaturated fatty acid is KPA.
  • the omega-3 polyunsaturated fatty acid comprises a mixture of DH ⁇ and EPA.
  • the composition including the omega-3 polyunsaturated fatty acid is a food. Although both liquid and solid foods are provided, solid foods are typically advantageous. Foods include both dry foods and wet foods. Some of the non-polyunsaturated fatty acid components of the food, and useful proportions, include those listed below .
  • Crude H ⁇ u. % to 20 wt. % of crude fiber on a dry matter basis, or 12 Fiber wt. % to 18 wt. %, or 14 wt. % to 16 %; or 10 wt. %. 10.5 wt. %, 1 1 wt. %. 1 1.5 wi %, 12 wt. %, 12.5 wt. %. 13 wt. %. 13.5 wl %. 14 wt. %, 14.5 wt. %. 15 wt. %. 1 5.5 wt. %, 16 wt. %. 16.5 wt. %. 17 wt. %, 17.5 wt. %, 18 wt. %. 18.5 wt. %. 19 wt. %, 10.5 wl. %,
  • Component Proportion of the composition (% of dry weight of composition or pa its per million)
  • the canine compositions of this invention include ingredients in an amount effective to enhance the animal ' s quality of hie.
  • Such compositions generally comprise:
  • the inv ention encompasses feline compositions that generally comprise:
  • compositions generally comprise.
  • (XV) ai least 0.05% (or 0.05% to 0.6%, or 0.1 % to 0.6%. or 0.1% to 0.4%) cystine.
  • compositions generally comprise:
  • (xviii) at least .05 (or 0.05 ppm to 75(K) ppm, or 250 to 3600, or 250 ppm to 1650 ppm, or 5 ppm to 225 ppm. or 0 05 ppm to 2.4 ppm) antioxidant, and
  • [001561 at least 1000 ppm (or 1000 ppm to 5000 ppm, 3300 ppm to 5000 ppm, or 2(K)O ppm to 3000 ppm, or 30(K) ppm to 4000 ppm) choline.
  • compositions generally comprise:
  • DHA 0.2%) DHA, and (ii) at least 0.1% (or 0.1% to 0.5%, or 0.2% Io 0.5%, or 0.2% to
  • ⁇ xx) at least 50 ppm (or 50 ppm to 500 ppm, or 100 ppm to 5(K) ppm, or
  • Win at least 50 ppm (o ⁇ 50 ppm to 500 ppm, or 200 ppm to 500 ppm, or
  • [0017Oj (g) at least 0 4% (or 0 4°.» to 2%, or 0.9% to 2%, or 0 9% to 1 2%)
  • compositions generally comprise.
  • (XXV ) at least 600 ppm ⁇ or 600 ppm to 24(M) ppm, or 12(>0 ppm to 2400 ppm, or 1260 ppm to 157 ⁇ ppm) taurine, and
  • (xxx) at least 200 ppm (or 200 to 750 ppm, or 400 ppm to 750 ppm, or 400 to 525 ppm) carnitine, and
  • the invention encompasses methods for treating or preventing diseases and disorders, including the administration of the compositions of the invention that are effective in modulating the expression and/or activity of proteins associated with obesity in animals both in vitro and in vivo.
  • the inventors have surprisingly found that Uw compositions of the invention are effective in modulating proteins associated with obesity in animals. Without being limited by theory, it is believed that modulation of protein expression and/or activity associated with obesity in animals is useful in treating or preventing a disorder associated with abnormal blood glucose levels, weight gain, or fat depot levels.
  • the invention further encompasses compositions and formulations that are useful in modulating protein activity in overweight and/or obese animals
  • lite invention also encompasses methods of modulating protein or gene activity including administering subject, preferably to a companion mammal in need of said treatment or prevention a therapeutically or prophy tactical Iy effective amount of a composition to modulate the activity of the protein or gene associate with obesity in the subject.
  • the agent for modulating lyn kinase activity is a compound of the invention.
  • a composition of the invention is administered to a mammal, preferably a companion animal, with a cardiovascular disease, a dyslipidemia, a dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (i.e. , Syndrome X), a PPAR-associated disorder, septicemia, a thrombotic disorder, type Il diabetes, obesity, pancreatitis, hypertension, a renal disease, or inflammation.
  • a cardiovascular disease a dyslipidemia, a dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (i.e. , Syndrome X), a PPAR-associated disorder, septicemia, a thrombotic disorder, type Il diabetes, obesity, pancreatitis, hypertension, a renal disease, or inflammation.
  • treatment refers to an amelioration of a disease or disorder, or at least one discernible symptom thereof, preferably associated with obesity.
  • treatment or “treating” refers to an amelioration of at least one measurable physical parameter, not necessarily discernible by the animal.
  • treatment or “treating” refers to inhibiting the progression of a disease or disorder, either physically, e.g., stabilization of a discernible symptom, physiologically, e.g., stabilization of a physical parameter, or both.
  • treatment or “treating” refers to delaying the onset of a disease or disorder.
  • compositions of the invention are administered to a patient, preferably a companion animal, as a preventative measure against such diseases.
  • prevention' or “preventing” refers to a reduction of the risk of acquiring a given disease or disorder.
  • the compositions of the present invention are administered as a preventative measure to a patient, preferably a companion animal having a genetic predisposition to a cardios asc ⁇ iar disease, a dyslipidemia. a dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome ⁇ i.e..
  • compositions of the invention are administered as a preventative measure to a companion animal having a predisposition to a cardiovascular disease, a dyslipidemia, a dysiipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (/. ⁇ .' , Syndrome X), a PPAR- associated disorder, septicemia, a thrombotic disorder, type II diabetes, obesity, pancreatitis, hypertension, a renal disease, or inflammation.
  • the compositions of the invention may be used for the prevention of one disease or disorder and concurrently treating another (e.g. , prevention of obesity while treating diaheies; prevention of inflammation while treating a cardiovascular disease).
  • the invention provides methods for the treatment or prevention of a cardiov ascular disease, comprising administering to a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle.
  • the cardiovascular disease is associated with abnormal/altered protein expression.
  • cardiovascular diseases' refers to diseases of the heart and circulatory system, These diseases are often associated with dislipoproteinemias and/or dyslipidemias.
  • Cardiovascular diseases which the compositions of the invention are useful for preventing or treating include, but are not limited to, arteriosclerosis; atherosclerosis; stroke; ischemia; endothelium dysfunctions, in particular those dysfunctions affecting blood vessel elasticity: peripheral vascular disease; coronary heart disease; myocardial infarction; cerebral infarction and restenosis.
  • the present invention provides methods for the treatment or prevention of a dyslipidemia comprising administering to a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle.
  • the dyslipidemia is associated with abnormal/altered lyn kinase activity and or expression.
  • the term "dyslipidemias” refers to disorders ihal lead to or are manifested by aberrant levels of circulating lipids. To (he extent that levels of lipids in the blood are too high, the compositions of the invention are administered to a companion animal to restore normal levels. Normal 1e ⁇ els of lipids are reported in medical treatises known to those of skill in the art.
  • recommended blood leseis of LDL, HDL, free triglycerides and others parameters relating to lipid metabolism can be found at the web site of the American Heart Association and that of the National Cholesterol Education Program of the National Heart, Lung and Blood Institute.
  • the recommended level of HDL cholesterol in the blood is above 35 mg dL; the recommended level of LDL cholesterol in the blood is below 130 mg/dL; the recommended LDL:HDL cholesterol ratio in the blood is below 5: 1. ideally 3.5: 1 ; and the recommended level of free triglycerides in the blood is less than 200 mg/dL
  • Dyslipidemias which the compositions of the invention are useful for preventing or treating include but are not limited to hyperlipidemia and low blood levels of high density lipoprotein (MDL) cholesterol.
  • the hyperlipidemia for prevention or treatment by the compounds of the present invention is familial hypercholesterolemia; familial combined hyperlipidemia; reduced or deficient lipoprotein lipase levels or activity, including reductions or deficiencies resulting from lipoprotein lipase mutations; hypertriglyceridemia; hypercholesterolemia; high blood levels of ketone bodies (c. ⁇ ., ⁇ -OH butyric acid); high blood levels of Lp(a) cholesterol; high blood levels of low density lipoprotein (LDL) cholesterol; high blood levels of very low density lipoprotein (VLDL) cholesterol and high blood levels of non-este ⁇ fied fatty acids.
  • the present invention further provides methods for altering lipid metabolism in a patient, for example, reducing LDL in the blood of a companion
  • the invention provides methods for the treatment or prevention of a dysiipoproteinemia comprising administering to a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle.
  • dysiipoproteinemias refers to disorders that lead to or are manifested by aberrant levels of circulating lipoproteins.
  • levels of lipoproteins in the blood are (oo high, the compositions of the invention are administered to a patient to restore normal levels.
  • levels of lipoproteins in the blood are loo low.
  • the compositions of the invention are administered Io a patient to restore normal levels. Normal levels of lipoproteins are reported in medical treatises known to those of skill in the art.
  • Dyslipoproieinemias which the compositions of the present invention are useful for preventing or treating include, but are not limited to, high blood levels of LDL; high blood levels of apolipoprotein B (apo B): high blood levels of Lp(a); high blood levels of apo(a); high blood levels of VLDL; low blood levels of HDL; reduced or deficient lipoprotein lipase levels or activity, including reductions or deficiencies resulting from lipoprotein lipase mutations; hypoalphalipoproteinemia; lipoprotein abnormalities associated w ith diabetes; lipoprotein abnormalities associated with type 11 diabetes, obesity; lipoprotein abnormalities associated w ith Alzheimer's Disease; and familial combined hyperlipidemia.
  • apo B apolipoprotein B
  • Lp(a) high blood levels of Lp(a)
  • apo(a) high blood levels of apo(a)
  • high blood levels of VLDL low blood levels of HDL
  • reduced or deficient lipoprotein lipase levels or activity including reduction
  • the invention provides methods for the treatment or prevention of a glucose metabolism disorder, comprising administering Io a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle.
  • glucose As used herein, the term "glucose
  • compositions of the invention refers to disorders that lead io or are manifested by aberrant glucose storage and/or tin Ii /at ton.
  • indicia of glucose metabolism ⁇ tf., blood insulin, blood glucose
  • the compositions of the invention axe administered to a patient to restore normal levels
  • indicia of glucose metabolism are too low.
  • the compositions of the invention are administered to a patient to restore normal levels.
  • Normal indicia of glucose metabolism are reported in medical treatises know n to those of skill in the art,
  • the glucose metabolism disorder is associated with abnormal/altered lyn kinase activity and or expression.
  • Glucose metabolism disorders which the compositions of the present invention are useful for preventing or treating include but ate not limited to impaired glucose tolerance; insulin resistance; insulin resistance related breast, colon or prostate cancer; diabetes, including but not limited to non-insulin dependent diabetes meUitus (NlDDM), insulin dependent diabetes mellitus (IDDM). gestational diabetes mellitus (GDM), and maturity onset diabetes of the young (MODY); pancreatitis; hypertension; polycystic ovarian disease; and high levels of blood insulin and or glucose.
  • NlDDM non-insulin dependent diabetes meUitus
  • IDDM insulin dependent diabetes mellitus
  • GDM gestational diabetes mellitus
  • MODY maturity onset diabetes of the young
  • pancreatitis hypertension
  • polycystic ovarian disease and high levels of blood insulin and or glucose.
  • the invention further provides methods for altering glucose metabolism in a patient, for example to increase insulin sensitivity and/or oxygen consumption of a companion animal, said methods comprising administering to the companion animal a composition comprising a compound of the invention in an amount effective to alter glucose metabolism.
  • treatment or prevention of Syndrome X or Metabolic Syndrome encompasses treatment or prevention of a symptom associated with metabolic syndrome including, but not limited to, impaired glucose tolerance, hypei tension and dyslipidemia and/or dislipoproteinemia.
  • the metabolic syndrome is associated with abnormal/altered fyu kinase activity and/or expression
  • Metabolic syndrome is characterized by a group of metabolic risk factors in a person. Risk factors that are associated with metabolic syndrome that can be
  • compositions comprising a compound of the imemiott include, but are not limited to, central obesity (Le,, excessive fat tissue in and around the abdomen); atherogenic dyslipidemia (blood fat disorders - mainly high triglycerides and low HDL cholesterol - that foster plaque buildups in artery- walls); raised blood pressure ( 130 85 mmMg or higher); insulin resistance or glucose intolerance (the body can't properly use insulin or blood sugar): prothrombotic state (e.g.. high fibrinogen or plasminogen activator inhibitor
  • central obesity Le, excessive fat tissue in and around the abdomen
  • atherogenic dyslipidemia blood fat disorders - mainly high triglycerides and low HDL cholesterol - that foster plaque buildups in artery- walls
  • raised blood pressure 130 85 mmMg or higher
  • insulin resistance or glucose intolerance the body can't properly
  • compositions of the invention are therefore useful hi Heating or preventing metabolic syndrome and disorders and risk factors associated with metabolic syndrome.
  • treatment or prevention of type Il diabetes encompasses treatment or prevention of a complication associated with type II diabetes including, but not limited to, retinopathy (/.t ⁇ , blindness); neuropathy (r.c, nerve damage) which leads to foot ulcers, gangrene, and amputations: kidney damage, which leads to dialysis: and cardiovascular disease.
  • retinopathy /.t ⁇ , blindness
  • neuropathy r.c, nerve damage
  • kidney damage which leads to dialysis: and cardiovascular disease.
  • cardiovascular disease cardiovascular disease
  • Type 11 diabetes is associated with obesity and with aging. It is a lifestyle- dependent disease, and has a strong genetic component (concordance in twins is 80- 90%). The problem seems not so much in insulin production, but that when the insulin reaches its target cells, it doesn't work correctly.
  • Most Type II diabetes patients initially have high insulin levels along with high blood sugar. However, since sugar signals the pancreas to release insulin, Type II diabetics eventually become resistant to that signal and the endocrine-pancreas soon will not make enough insulin.
  • These companion animals end up managing the disease with insulin and they n ⁇ much higher doses because they are resistant to it. ⁇ 00226) When a companion animal takes in a high load of sugar, the sugar stimulates the pancreas to release insulin.
  • the targets for insulin are muscle, fat, and us er cells. These cells have insulin receptor sites on the outside of the ceil membrane. For most companion animals, when insulin has bound to the receptors, a cascade of events begins, which leads to sugar being transported from the blood into the interior of the cell. In Type Il diabetics, even when insulin is present on the cell membrane, the process doesn't work. The glucose is never taken tip into the cell and remains in the bloodstream.
  • the liver is responsible for glucose production and insulin is the regulator)' agent of production.
  • a high blood sugar content causes the pancreas to release insulin, and the insulin should signal the liver to stop making sugars. But. in diabetics, there's resistance to that signal and the liver keeps producing glucose. Hyperglycemia leads to glucose toxicity.
  • compositions comprising a compound of the invention are therefore useful in treating or preventing type II diabetes or complications arising from type 11 diabetes and disorders and risk factors associated with metabolic syndrome.
  • Complications of diabetes include, but are not limited to, diabetic neuropathy, diabetic retinopathy, erectile dysfunction, and kidney disease
  • treatment or prevention of obesity encompasses treatment or prevention of a complication associated with obesity.
  • Complications of obesity include, but are not limited to. hypercholesterolemia, hypertension, dyslipidemia (for example, high total cholesterol or high levels of triglycerides), type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea and respiratory problems, and some cancers (endometrial, breast, and colon).
  • the obesity is associated with abnormal altered lyn kinase activity and/or expression
  • the present invention provides methods for the treatment or prevention of septicemia, thrombotic disorders, pancreatitis, hypertension, inflammation, and impotence, comprising administering to a patient a therapeutically effective amount of a composition comprising a compound of the invention and a pharmaceutically acceptable vehicle.
  • these disorders are associated with abnormal altered lyn kinase activity and/or expression
  • treatment or prevention of septicemia encompasses treatment or prevention of septic .shock.
  • treatment or prevention of thrombotic disorders encompasses treatment or prevention of high blood levels ot fibrinogen and promotion of fibrinolysis.
  • compositions of the invention can be administered to an individual to promote weight reduction of the individual.
  • the kit comprises a v trtual package
  • the kit is limited to instructions in a virtual environment in combination with one or more physical kit components.
  • the kit contains probes and or other physical components and
  • the instructions for using the probes and other components are available via the internet.
  • the kit may contain additional ilems such as a device for mixing samples, probes, and reagents and device for using the kit, e.g., test tubes or mixing utensils.
  • additional ilems such as a device for mixing samples, probes, and reagents and device for using the kit, e.g., test tubes or mixing utensils.
  • the present invention provides a means for communicating information or instructions for one or more of (1 ) using the polynucleotides of the present invention for delecting the expression of genes differentially expressed in overweight animals compared to lean animals in a sample.
  • the means comprises a document, digital storage media, optical storage media, audio presentation, or visual display containing the information or instructions.
  • the communication means is a
  • Useful information includes one or more of ⁇ 1) methods for promoting the health and wellness of animals and t,2) contact information for the animal ' s caregiv ers to use if they hase a question the invention and its use.
  • Useful instructions include techniques for using the probes, instructions for performing a gene expression assa>. and administration amounts and frequency for the substances. T he communication means is useful for instructing on the benefits of using the present invention.
  • RNA Ribonucleic Acid
  • Tissue samples that have been collected, fro/en in liquid nitrogen, and thawed are homogenized and processed using a TRl/ok ⁇ 1 RNA extraction method to produce good quality RNA which is then subjected to further genomic analysis.
  • Tissue Homogeni/ation Fill a container capable of holding liquid nitrogen with 3-4 scoops of liquid nitrogen Place a piece of fro/en tissue immediately into the aforementioned container (the tissue should be the si/e of a pea) and place the tissue into the appropriate labeled 5OmL polypropylene tube (that already contains 4mL TRl/ol>*C). Immediately begin homogenizaUon using the Ultra-Turra ⁇ T25 Power Homogeni/er. Homogenize on the highest setting (f>) for 10-15 seconds Cool the sample on ice for another 10- 15 seconds and then repeat. Continue until the tissue is fully homogenized and the solution is cloudy . Upon complete homogeni/ation. cap the 5OmL tube and return Io the ice. Incubate the homogenized tissues at room temperature for 5 minutes before proceeding with the isolation procedure.
  • RNA Isolation The procedures given in the Invitrogen instructions provided with the TRI/ol ⁇ reagent are generally followed. Separate the homogenized sample into four I mL aliquots in four l .5 ⁇ iL microcentrifuge tubes. Add 20OuL of chloroform to each ImL aliquot. Cap the tubes, vortex for 15 seconds and then shake up and down. The result should be a pink milky liquid. Incubate the tubes at room temperature for 2-3 minutes. Centrifuge the tubes for 15 minutes at 14,000 rpm and 4 0 C. Transfer the aqueous phase (top layer) to a sterile L5mL microcentrifuge tube.
  • the typical ⁇ oinme of the aqueous phase which should be transferred to the new tube is 50OuL. Be sure not to transfer any of the intermediate or lower phase.
  • Precipitate the RNA fiom solution by adding 50OuL of lsopropyl Alcohol to each microcentrifuge tube containing the aqueous layer. Shake the tubes up and down for at least 20 seconds, incubate the samples at room temperature for 10 minutes. Centrifuge die samples for 10 minutes, 14,000 rpm at 4T. Remove the supernatant carefully by aspirating off the liquid being we not to
  • RNA which is then used for future downstream genomic analysis. All work related to the culruring of the cells is to be done ⁇ nder strict aseptic conditions.
  • Buffer RPE (provided in the RNeasy Mini Kit)
  • Equipment/Materials RNeasy Mini Kit, QIAshredder spin columns,
  • Ethanoi Make 5OmL of 70% ethan ⁇ l b> adding 35m L absolute ethanoi to l 5mL deioro/ed, RNase-free svater.
  • IX PBS RNase-free water. Filter (he solution using a
  • RNA Isolation Centrifuge the QlAshredder spin columns at 14,000 rpm for 2 minutes. Discard the spin column but keep the collection tube and its contents. Add 6ihH.lL of 70% ethanoi to the collection Cube and mix well by pipetting (the total volume now :: l .2mL). Transfer 60OuL of the ceil lysate to an RNeasy mini column and centrifuge for 15 seconds at 14,000 rpm. Discard the How through but keep the collection tube and the spin column. Transfer the remaining volume of ceil iysate ⁇ 6(K)uL) to the spin column and repeat the centrifugal ion.
  • RNA 6000 Nano gel matrix RNA 6(X)O Nano dye concentrate
  • RNA 6000 Nano Marker (ail of the above reagents are contained in the RNA 6000
  • ⁇ 00254J Gene expression is analyzed using Asymetrix Canine 1 and Canine 2 GeneChip ⁇ " Arrays are available commercially from Affymetrix, Inc., Santa Clara, CA 95051. Total RNA is reverse transcribed into cDNA. The cDNA is used to generate cRNA which is fragmented and used as probes for GeneChip hybridization. The gene chip is washed and the hybridization signal is measured with an Affymetrix laser scanner. The hybridization data is then validated and normalized for further analysis.
  • Affymetrix provides most of the reagents and kit. Other reagents listed in the Aflymerrix Manual but not supplied in the kit may be obtained separately (refer to GeneChip Expression Analysis Technical Manual (701021 Rev.4) for details), RNase Zap-fc and deioni/.ed water.
  • Equipment Eppendorf microcentrifuge, 1.5mL DNase and RNase free sterile microcentrifuge tubes, 5OmL DNase and RNase free/sterile disposable polypropylene tubes, PlOOO, P200. P20, PlO and P2 Rainin Pipetman pipettes.
  • Procedure follow all procedures exactly as described in GeneChip Expression Analysis Technical Manual (Affymetrix Copyright 1999-2003). Use 5 microgram of total RNA for the first strand cDNA synthesis. Use either Peltier Thermal C) cler PTC-200 or heat block for temperature control on reactions and probe denaturing. The quality control is performed using RKA NanoDrop chips with BioAnalyer 2100. Use 100 Formal (Midi Array) for the canine geuechip.
  • Adipose tissue samples are obtained from 18 (3 lean and 15 fat) or lymphocytes obtained from 44 (12 lean and 32 fat) canine animals diagnosed as either v 'fat” or ''lean” using conventional methods.
  • the "fatness" or '"leanness" of an animal is determined based on measurements by DEXA using conventional methods or based on a 5 point body condition scoring system. For example, an animal is considered lean if it has a body condition score of 2 or 2.5 and or a DEXA total body fat percentage of 27% or less. An animal is considered to be overweight if it has a body condition score of 4 or higher and a total body fat percentage of 30% or higher.
  • lymphocytes were isolated using BD VactuainerxR CPT tM Cell Preparation Tube according to manufactuerers instructions and were also snap fro/en until needed.
  • the samples were alt analyzed using Affymetrix Canine-2 GetteChips* according to manufacturers recommendations in order to determine which genes are differentiall ⁇ expressed in overweight animals compared to lean animals.
  • Fold change > 1 implies probes are UP regulated in APP FAT samples.
  • PREUJCTtD Cams familiaris s tase 6; e 6. similar to acid phospha
  • PREOICTEO Can* familiaris (prot protein kinase B gamma-iike ein
  • CfeAffx.22670 alkaline phosphatase (AlP); XM 5353 liver/bone/
  • CfaAffx.6868.1 protein transcript s'aoant 1 XM 5442 (Xenopus
  • Cams famHlaris (transme similar to Serine protease hepsin crransmetnbfane mbrane
  • PRFOICTFD Cams fsmiliaris int siwii ⁇ r to HlV-I Tat interactive eractive
  • PREDICTCD Cams familiarls volt hypothetjcai protein age-
  • PREDICTCD Cams familiaris sponsiv similar to IMMUNE- e 1
  • LDH-B Cams familiars (LDH-B) similar to l-lacwte (LDH dehydrogenase 8 diain (LDN- h B) (LOH neart subunit) (LDH- eart
  • N-dnmaerin N (RhO- chlmeiin) (Alpha chlmefin) (A- GTFase- chlma ⁇ fi ⁇ ) (Rho- ⁇ TPase-
  • PREDICTCD Cams familiarls sirnilar to C-jurs-amino-terminal kinase interacting protein I mito ⁇ en- (JNK-interactirsg protein i) (JIP activated 1) (JNK MAP kinase scaffold protein protein I) ⁇ Istet-braln-J) (58-1! (Mitoge ⁇ -actJvatec- protein kinase 8 ⁇ aAfix.14768. kinase S-irsteracting prot ⁇ n 1) XM 5407 MAPK8I interacting
  • PREDICTCD Cams familiarls d protein, similar to microtubule* associated protein; RP/EB RP/EB
  • PR601CTED Cams familiaris ce sirnll ⁇ ir to minictwm ⁇ some maintenarsce protein 8 isoform complex
  • PREOICTEO Cams familiaris simitar to M ⁇ esirt (Membrane- organteing extension spfke
  • Cfa.S42.1.A1 G9 sialSdase (LOC481717); XM 5388 (lysosoma at 5.64E-02 5,00E-OO 1.36 mRNA 38 NEU1 sialidase)
  • Bos taurus nuclear receptor nuclear binding factor 2 mRNA (cDMA receptor done MGC: 143396
  • PREDICTCD Cams familiarls eoatio
  • CR ⁇ IS fawill ⁇ r ⁇ family 12 similar to Soiute carrier family (potassiu 12; member 7 (Etectroneutr ⁇ i m/chioride potassfum-chlorids cotransporter 4) (K-Ci transporte
  • solute carrier family 3 activators of dibasic and
  • PREDICTCD Cams familiarls neutral similar to soi ⁇ te ea>ner family amino 3 ⁇ activarors of (tibawc and ne ⁇ trai amino sod transport), acid
  • Cams familiaris siwii ⁇ r to Dual specificity protein phosphatase 24 Map serine/thre kinase ptiosphatase-like onine/tyro protein MK-STYX; (DkOl sin specWoty phosphatase e
  • transcript variant S XM 8631 factor transcript variant S XM 8631 factor
  • Bos tau ⁇ is zinc flrvger proteit ⁇ 180; mfWA (cDNA done zinc fing MGC: lStS2S er

Abstract

The invention encompasses compositions and methods for treating disorders and diseases associated with overweight. The application also encompasses genes differentially expressed in animals and particularly to genes differentially expressed in overweight animals compared to lean animals.

Description

COMPOSITIONS AND METHODS FOR TREATING DISORDERS ASSOCIATED WITH OVERWEIGHT ANIMALS
FIELD OF THE INVENTION
[0001] The invention encompasses compositions and methods for treating disorders and diseases associated with obesity. The application also encompasses genes differentially expressed in animals and particularly to genes differentially expressed in obese animals compared Io lean animals. The inv ention also encompasses compositions and methods for modulating the amount of fat in animals with targeted nutrition that is designed to affect, among others, key genes involved in fat metabolism. The invention further identifies bioacthe dietary components that individually or together can affect the expression and activity of key genes involved in fat metabolism.
BACKGROUND OF THE INVENTION
[0002] It is generally accepted in the scientific community that the regulation of gene expression plays a key role in the development of some diseases or conditions that affect an animal's health and well being. Similarly, the differential expression of genes is one factor in the development of such diseases and conditions and the evaluation of gene expression patterns has become recognized as crucial to understanding the development and control of such diseases and conditions at the molecular level. To advance the understanding of genes and their relationship to disease, a number of methods have been developed for studying differential gene expression, e.g., DNA microarrays, Expressed Sequence Tags (EST), serial analysis of gene expression (SAGE), subiractive hybridization, subtracthe cloning and differential display (DD) for mRNA. RNA-arbitrarily primed PCR (RAP-PCR), Representational Difference Analysis (RDA). two-dimensional gel electrophoresis, mass spectrometry. Reverse Phase protein array and arrays. [0003] Gene expression in overweight animals compared to lean animals has not been thoroughly investigated. Therefore, a need exists to identify genes and proteins that are differentially expressed in overweight animals compared to lean animals. Such genes, proteins, and their fragments would be useful for formulating a prognosis that an animal is likely to become fat, developing a diagnosis that an animal is fat, screening substances Io determine if lhey are likely to be useful for modulating the amount of adipose tissue on an animal, and using such substances to modulate the amount of adipose tissue on an animal.
[0004] Overweight animals can be defined as those animals having an excess of body adipose tissue. Generally, animals such as humans, canines, and felines weighing more than 15% of (heir ideal body weight are considered fat. The most common cause of an animal being fat is an over consumption of food tliat results in an excess intake of calories. However, there are other factors that cart increase an animal's chances for being fat. e.g.. lifestyle, health, eating habits, breed, spaying, and neutering. Also, the incidence of animals becoming overweight generally increases with age due to a general decrease in metabolic rate and in physical activity. Surv eys estimate that 25% of dogs in the United States that visit veterinary clinics are fat to the point of being obese. Studies have shown that overweight animals are significantly more at risk for diseases such as arthritis, heart disease, respiratory disease, diabetes, bladder cancer, hypothyroidism, and pancreatitis. [0005] Modulating the amount of adipose tissue on an animal, including preventing an animal from becoming overweight or treating a overweight animal to reduce the amount of adipose tissue on the animal or treating a lean animal to increase the amount of adipose tissue in the animal, is difficult. Increasing the amount of adipose tissue on an animal usually involves increasing the amount of food consumed. The most effective and easiest way to prevent an animal from becoming overweight or to reduce the amount of fat on an animal is with dietary restriction and exercise. However, it is often difficult to ensure compliance with diet and exercise programs. Other methods involve the use of dntgs such as phenteπnine, fenfluramine, sibutramine. orlistat, and phenylpropanolamine. Unfortunately, side effects occur with these drugs. For example, the administration of fenfluramine and phentermine for the treatment of human obesity can result in cardiac valve damage in humans. Sibutramine can increase blood pressure and orlistai may have unpleasant gastrointestinal side effects.
[0006] Given the problems with current methods for dealing with adipose tissue on an animal, the inventors have developed methods and compositions useful for treating diseases and disorders in animals and in formulating a prognosis that an animal is likely to become fat, developing a diagnosis that an animal is fat. screening substances to determine if they are likely to be useful for modulating the amount of adipose tissue on an animal, and using such substances to modulate the amount of adipose tissue on an animal.
SUMMARY OF THE INVENTION
[0007] The imention encompasses compositions and methods useful in treating disorders in companion animals iu need thereof.
[0008] In one embodiment, the invention encompasses a canine pet food composition comprising an effective amount of one or more ingredients that interfere with the expression of one or more genes differential Iy expressed in overweight animals compared to lean animals, wherein said one or more ingredients that interfere with the expression of one or more genes comprise 26 wt. % to 35 wi. % of crude protein on a dry matter basis, 7.5 wt. % to 8.5 wt. % of crude fat on a dry matter basis. 20 wt. % to 30 wt. % of total dietary fiber on a dry matter basis, and 10 wt. % to 20 wt. % of crude fiber on a dry1 matter basis. [0009] In another embodiment, the invention encompasses a feline pet food composition comprising an effective amount of one or more ingredients that interfere with the expression of one or more genes differentially expressed in overweight animals compared to lean animals, wherein said one or more ingredients that interfere with the expression of one or more genes comprise: 30 wt. % to 37 wi. % of crude protein on a dry matter basis. 7,5 wt. % to 9 w t. % of crude fat on a dry matter basis, 30 wt. % to 35 wt. % of total dietary fiber on a dry matter basis, and 20 wi. % to 25 wt. % of crude fiber on a dry matter basis. jøølOJ Another embodiment encompasses a method of treating or preventing insulin resistance in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0011] Another embodiment encompasses a method of treating or preventing pancreatitis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0012] Another embodiment encompasses a method of treating or preventing hypothyroidism in a companion animal in need thereof, for example, a canine, or feline, w ith a composition of the invention. [0013] Another embodiment encompasses a method of treating or presenting osteoarthritis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0014] Another embodiment encompasses a method of treating or preventing dyslipidemia in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0015] Another embodiment encompasses a method of treating or presenting hypertension in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0016] Another embodiment encompasses a method of treating or preventing ocular disorders in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0017] Another embodiment encompasses a method of treating or preventing altered kidney function in a companion animal in need thereof, for example, a canine or feline, with a composition of ihe invention.
[0018] Anoiher embodiment encompasses a method of treating or preventing respiratory' in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0019] Another embodiment encompasses a method of treating or preventing artherosclerosis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0020] Another embodiment encompasses a method of treating or presenting diabetes mellitus in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0021] Another embodiment encompasses a method of treating or preventing urinary tract disease in a companion animal in need thereof, for exajtrφie, a canine or feline, with a composition of the invention.
[0022] Another embodiment encompasses a method of treating or presenting hepatic lipidosis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0023] Anoiher embodiment encompasses a method of treating or preventing hepatic dyslipidemia in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention. [0024] Another embodiment encompasses a method of treating or presenting hepatic lipidosis in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0025] Another embodiment encompasses a method of treating or preventing neoplasia in a companion animal in need thereof, for example, a canine or feline, with a composition of the inv ention.
[0026] Another embodiment encompasses a method of treating or presenting oral/dental disease m a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0027] Another embodiment encompasses a method of treating or preventing dermalopathy in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0028] Another embodiment encompasses a method of treating or preventing lameness in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0029] Anoiher embodiment encompasses a method of treating or preventing hyperlipidemia in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0030] Another embodiment encompasses a method of treating or preventing glucose metabolism disorders in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0031 ] Another embodiment encompasses a method of treating or presenting coronary disease in a companion animal in need thereof, for example, a canine or feline, with a composition of the invention.
[0032] Another embodiment of the invention encompasses one or more genes or gene segments that are differentially expressed in overweight animals compared to lean animals.
[0033] Another embodiment of the invention encompasses combinations of two or more polynucleotides or polypeptides that are differentially expressed in overweight animals compared to lean animals.
[0034] Another embodiment of the invention encompasses compositions of two or more polynucleotide or polypeptide probes suitable for detecting the expression of genes differentially expressed in overweight animals compared to lean animals and devices such as substrate arrays containing the probes. [0035] Another embodiment of the invention encompasses methods and compositions for detecting the differential expression of one or more genes differentially expressed in overweight animals compared to lean animals in a sample.
[0036] Another embodiment of the invention encompasses methods for measuring the effect of a test substance on the expression profile of one or more genes differentially expressed in overweight animals compared to lean animals as a method for screening a test substance to determine if it is likely to be useful for modulating the amount of adipose tissue on an animal.
[0037] Another embodiment of the invention encompasses methods for formulating a prognosis that an animal is likely to become overweight or developing a diagnosis that an animal is fat.
[0038] Another embodiment of the invention encompasses methods and compositions for modulating tibe expression of one or more genes differentially expressed in overweight animals compared Io lean animals or for modulating the amount of adipose tissue on an animal.
[0039] One or more of these embodiments are achieved using novel combinations of 433 polynucleotide probes representing genes and gene segments that are differentially expressed in the adipose tissue of overweight animals compared to the adipose tissue of lean animals (Table 1 ). In addition, one or more of these embodiments are achieved using novel combinations of 1703 polynucleotide piobes representing genes and gene segments that are differentially expressed in lymphocytes taken from ov erweight animals compared to lymphocytes taken from lean animals {Table 2). Furthermore, one or more of these embodiments are achieved using novel combinations of the polynucleotide probes representing the genes and gene segments that are differentially expressed in overweight and lean dogs and are considered io be key genes for fatty acid metabolism (Table 3). The polynucleotides are used to produce compositions, probes, devices based on the probes, and methods for determining the status of polynucleotides differentially expressed in overv, eight animals compared to lean animals useful for achieving the above-identified objects, e.g., proguosing and diagnosing conditions relating to animal adipose tissue and for screening substances to determine if they are likely to be useful for modulating the amount of adipose tissue on an animal. Such substances, once identified, may be used to modulate the amount of adipose tissue on an animal. Various kits comprising combinations of probes, devices utilizing the probes, and substances are also provided.
[0040] Ii is also an embodiment of tin's invention to encompass methods to modulate the amount of adipose tissue in an animal in vivo by administration of composition of the invention that is shown to modulate the expression of genes involved in fat metabolism.
[0041] It is also an embodiment of the invention to modulate various canine biomarkers related to obesity by administering a composition of the invention to an animal in need thereof in an amount effective to modulate the biomarker. Examples of biomarkers related to obesity that can be modulated include, but are not limited to, glucose, insulin. GLP-I, IGF-L cholesterol, triglycerides, LUL, chylomicrons, alkaline phosphatase, type-2 cartilage synthesis, leptin, ghrelin, and combinations thereof.
[0042] Other and further objects, features, and advantages of lhe preseni invention will be readily apparent to those skilled in the art.
BRIEF DESCRIPTION OF THE FIGURES
[0043] FIGURE 1 shows lhe result for weight loss of dogs fed the formula of the present invention as compared to a control weight loss formula. [0044] Figure 2 shows the shift in gene profile in dogs fed the formula of (he present invention as compared to lean dogs, obese
DETAILED DESCRIPTION OF THE INVENTJON
Definitions
[0045] The term "animal" means a human or other animal, including avian, bovine, canine, equine, feline, hicrine, murine, ovine, and porcine animals, that has adipose tissue. When the term is used in the contexl of comparing overweight to lean animals, the animals that are compared are animals of the same species and possibly of the same race or breed. Io preferred embodiments, the animal is a canine or feline, most preferably a canine.
[0046] The leπn "antibody" means any immunoglobulin thai binds to a specific amigen. including IgG, IgM IgA. IgD, and IgE antibodies. The term includes polyclonal, monoclonal, monovalent, humanized, heteroconjugate, antibody compositions with polyepitopic specificity, chimeric, bispecific antibodies, diabodies, single-chain antibodies, and antibody fragments such as Fab, Fab". F(ab' );. and Fv, or other amigen-binding fragments.
[0047] The term "array" means an ordered arrangement of at least two probes on a substrate. At least one of the probes is a control or standard and at least one of the probes is a diagnostic probe. The arrangement of from two or more probes (there are arrays, chips and other platforms now that go over 40,000) on a substrate assures that the si/e and signal intensity of each labeled complex formed between a probe and a sample polynucleotide or polypeptide is individually distinguishable. [0048] The term "body condition score" (BCS) means a method for body- composition analysis based upon an animal's body si/e and shape. Sev eral methods are known to skilled artisans* e.g.. methods disclosed in US. Patent No. 6,691,639 and in the reference entitled "Small Animal Clinical Nutrition", 4* Edition, in Chapter 13 (ISBN 0-945.S37-05-4).
The term " Body Mass Index" (BMl) means an animal's weight (in kilograms) divided by its height (in meters) squared
[0049] The term "DEXA" means body composition analysis dual-energy X-ray absorptiometry.
[0050] The term "differential expression" or "differentially expressed'' means increased or upregulaled gene expression or means decreased or dowmegulated gene expression as detected by the absence, presence, or at least a 1.3-fold change in the amount of transcribed messenger RNA or translated protein in a sample. [0051] The term k'faf as applied to an animal means any animal that is determined to have no excess amount of body adipose tissue or an animal that is prone to developing an excess amount of body adipose tissue using techniques and methods known to health care providers and other skilled artisans. An animal is prone to becoming overweight if the animal has an inclination or a higher likelihood of developing excess adipose tissue when compared to an average animal in ihe general population. Generally, without limiting the definition, an animal is considered overweight if (1 ) the animal has a BMl of 25 or more ^a number considered to include "overweight" and "obese" in some methods of characterizing animal conditions). (2) the animal's weight is 15Ho or mote than its "ideal" body weight as defined by health care professionals or related skilled artisans, <3) an animal's percent body fat is 2?% or more as determined by DEXA, or (4) an animal has a body condition score of more than 3 as determined by skilled artisans using the method disclosed in '"Small Animal Clinical Nutrition.", 4ltl Edition, in Chapter 13 (fSBN 0-945837-05-4) or its equivalent using other BCS methods.
[0052] The term "fat-associated genes" means all or a subset of the genes identified in tables I and 2. particularly the geaes represented by the 433 probe sequences that are differentially expressed between adipose tissue taken from overweight animals and adipose tissue taken from lean animals as well as the genes represented by the 1703 probe sequences that are differentially expressed between the lymphocytes iaken from overweight animals and the lymphocytes taken from lean animals.
[0053] The term "key genes" means all or a subset of genes identified in table 3 [0054] The term "fold" when used as a measure of differential gene expression means an amount of gene expression in an animal that is a multiple or a fraction of gene expression compared to the amount of gene expression in a comparison animal, e.g.. a overweight animals compared to a lean animal. For example, a gene thai is expressed ihree times as much in the animal as in the comparison animal lias a 3 fold differential gene expression and the gene is said to be up-regulated. On the other hand a gene that is expressed one-third as much in the animal as in the comparison animal also has a 3 fold differential gene expression and is said to be dow n-reguhued.
[0055] The term "fragment" means ( I ) an oligonucleotide or polynucleotide sequence that is a portion of a complete sequence and that has die same or similar activity for a particular use as the complete polynucleotide sequence or (2) a peptide or polypeptide sequence that is a portion of a complete sequence and that has the same or similar activ ity for a particular use as the complete polypeptide sequence. Such fragments can comprise any number of nucleotides or amino acids deemed suitable for a particular use. Generally, oligonucleotide or polynucleotide fragments contain at least 10, 50, 100. or 1000 nucleotides and polypeptide fragments contain at least 4. 10, 20, or 50 consecutive amino acids from the complete sequence. The term encompasses polynucleotides and polypeptides variants or" the fragments.
[0056] The term "gene" or "genes" means a complete or partial segment of DNA invoked in producing a polypeptide, including regions preceding and following the coding region (leader and trailer) and intervening sequences (introm) between individual coding segments (exons). The term encompasses any DKA sequence that hybridizes to the complement of gene coding sequences. [0057] The term "genes differentially expressed in overweight animals" means genes from which the amount of inRNA expressed or die amount of gene product translated from the mRNA is detectøbly different, either more or less, in tissue from overweight animals as compared to lean animals
[0058] The term "homoiog" means ( t) a polynucleotide, including polynucleotides from the same or different animal species, having greater than 30%. 50%. 70%, or 90% sequence similarity to a polynucleotide identified in tables 1. 2. 3 and 5 and having the same or substantially the same properties and performing the same or substantially the same function as the complete polynucleotide, or having the capability of specifically hybridizing to a polynucleotide identified in tables 1. 2. 3 and 5 under stringent conditions or (2) a polypeptide, including polypeptides from the same or different atu'mal species, having greater than 301Jo, 50% . 70%. or <)()% sequence similarity to a polypeptide identified by the expression of polynucleotides identified in tables 1 , 2, 3 and 5 and having the same or substantially the same properties and performing the same or substantially the same function as the complete polypeptide, or having the capability of specifically binding to a polypeptide identified b> the expression of polynucleotides identified in tables 1 , 2, 3 and 5. Sequence similarity of two polypeptide sequences or of two polynucleotide sequences is determined using methods known to skilled artisans, e.g., the algorithm of Karlin and Altschul (Proc. Natl. Acad. Sci. USA 87:2264-2268 ( 1990)}. Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul et al. (J. MoI. Biol. 215:403-410 ( 1990)). To obtain gapped alignments lor comparison purposes. Gapped Blast can
K) be utilised as described in Altschυl et al. (Nucl. Acids Res. 25: 3389-3402 (1997)). When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) are used. See hup: ww.ncbi.iilm.nih.gov.
[0059] The leπυ "hybridization complex" means a complex thai is formed between sample polynucleotides when the purines of one polynucleotide hydrogen bond with the pyrimidines of the complementary polynucleotide, e.g.. 5"-A-G-T-C- -V base pairs with 3'-T-C-A-G-S*. The degree of cømplementarily and the use of nucleotide analogs affect the efficiency and stringency of hybridization reactions.
[0060] The term "in conjunction"' means that a drug, food, or other substance is administered to an animal (1 ) together in a composition, particularly food composition, or (2) separately at the satne or different frequency using the same or different administration routes at the same time or periodically. "Periodically" means that the substance is administered on a dosage schedule acceptable for a specific substance, "the same lime" generally means that die substance (food or drug) is administered at the same time or within 72 hours of each other. '"In conjunction" specifically includes administration schemes wherein substances such as drugs are administered for a prescribed period and compositions of the present invention are administered indefinitely.
[0061] The term "lean" as applied to an animal means any animal that is determined not to be overweight using techniques and methods known to health care providers and other skilled artisans. Generally, without limiting the definition, an animal is considered lean if ( 1) the animal has a BMl of less than 25 or (2) the animal's weight is less than 15% more than its "ideal" body weight as defined by health care professionals or related skilled artisans, (3) an animal's percent body fat is less than 27% as determined by DEXA, or (4) an animal lias a body condition scoie of 3 or less as determined by skilled artisans using the method disclosed in "Small Animal Clinical Nutrition". 4'1' Edition, in Chapter 13 {ISBN 0-945837-05- 4) or it equivalent using other BCS methods.
[0062] The term "modulating the amount of adipose tissue on an animal" means causing the animal to lose adipose tissue, causing the animal to gain adipose tissue, or causing the animal to maintain the amount of adipose tissue on the animal if the animal is prone to gaining or losing adipose tissue. Thus, modulating the amount of
U adipose tissue on an animal encompasses preventing a lean animal from becoming overweight and treating a overweight animal to reduce the amount of adipose tissue on the animal, as well as treating a lean animal to add adipose tissue in appropriate circumstances, e.g., when treating a lean animal that is determined by skilled artisans to be so underweight that the addition of adipose tissue is desirable. Conventional methods may be used to assess the amount of adipose tissue on an ammal, as well as to determine the animal's lean muscle mass and /or bone mineral content, information which may be of relevance in such an assessment. [0063] The term "polynucleotide" or "oligonucleotide" means a polymer of nucleotides The term encompasses DNA and RNA (including cϋN'A and mRNA) molecules, either single or double stranded and. if single stranded, its complementary sequence in either linear or circular form. The term also encompasses fragments, variants, homologs, and alleles, as appropriate for the sequences that have the same or substantially the same properties and perform the same or substantially the same function as die original sequence. The sequences may be fully complementary (no mismatches) when aligned or may have up to a 30% sequence mismatch. Preferably, for polynucleotides, the chain contains from 50 to 10,000 nucleotides, more preferably from 150 to 3,500 nucleotides. Preferably, for oligonucleotides, the chain contains from 2 to 100 nucleotides, more preferably from 6 to 30 nucleotides. The exact si/e of a polynucleotide or oligonucleotide will depend on various factors and on the particular application and use of the polynucleotide or oligonucleotide. The term includes nucleotide polymers that are synthesized and that are isolated and purified from natural sources. The term "polynucleotide" is inclusive of "oligonucleotide." [0064] The term "polypeptide," "'peptide," or "'protein" means a polymer of amino acids. The term encompasses naturally occurring and non-naturally occurring (synthetic) polymers and polymers in which artificial chemical mimetics are substituted for one or more amino acids. The term also encompasses fragments,, valiants, and homologs that have the same or substantially the same properties and perform the same or substantially the same function as the original sequence. The term encompass polymers of any length, preferably polymers containing from 2 to 1000 amino acids, more preferably from 5 to 5(M) amino acids. The term includes amino acid polymers thai are synthesized and tliat are isolated and purified from natural sources.
[0065] The term "probe" means (1 ) an oligonucleotide or polynucleotide, either RNΛ or DNA. whether occurring naturally as in a purified restriction enzyme digest or produced synthetically, that is capable of annealing with or specifically hybridizing to a polynucleotide with sequences complementary to the probe or (2) a peptide or polypeptide capable of specifically binding a particular protein or protein fragment to the substantial exclusion of other proteins or protein fragments. Au oligonucleotide or polynucleotide probe may be either single or double stranded. The exact length of the probe will depend upon many factors, including temperature, source, and use. For example, for diagnostic applications, depending on the complexity of (he target sequence, an oligonucleotide probe typically contains U) to 100, 15 to 50. or 15 to 25 nucleotides. In certain diagnostic applications, a polynucleotide probe contains 100-1000, 300-600, nucleotides, preferably 300 nucleotides. The probes herein are selected to be "substantia Hy" complementary to different strands of a particular target sequence. This means that the probes must be sufficiently complementary to specifically hybridi/e or anneal with their respective target sequences under a set of predetermined conditions. Therefore, the probe sequence need not reflect the exact complementary sequence of the target. For example, a noncomplementary nucleotide fragment may be attached to the 5" or 3' end of the probe, with the remainder of the probe sequence being complementary to the target sequence. Alternatively, nonconiplementary bases or longer sequences can be interspersed into the probe provided that the probe sequence has sufficient complementarity with the sequence of the target polynucleotide to specifically anneal to the target polynucleotide. A peptide or polypeptide probe may be any molecule to which the protein or peptide specifically binds, including DNA (for DNA binding proteins), antibodies, cell membrane receptors, peptides, cofactors. lectins, sugars, polysaccharides, cells, ceil membranes, organelles and organella! membranes.
[0066] The term "sample" means any animal tissue or fluid containing, e.g., polynucleotides, polypeptides, antibodies, metabolites, and the like, including cells and other tissue containing DKA and RNA. Examples include adipose, blood, cartilage, connective, epithelial, lymphoid, muscle, nervous, sputum, and the like. A sample may be solid or liquid and may be DNA, RNA, cDNA, bodily fluids such as blood or urine, ceils, cell preparations or soluble fractions or media aliqυots thereof, chromosomes, organelles, and the like.
[0067] The term "single package" means that the components of a kii are physically associated in or with one oi more containers and considered a unit for manufacture, distribution, sale, or use. Containers include, but are not limited to, bags, boxes, bottles, shrink wrap packages, stapled or otherwise affixed components, or combinations thereof. A single package may be containers of individual food compositions physically associated such that they are considered a unit for manufacture, distribution, sale, or use.
[0068] The term "useful variations" means (1 ) for a polynucleotide, the complements of the polynucleotide; the homologs of the polynucleotide and its complements; the variants of the polynucleotide, its complements, and its homologs: and the fragments of the polynucleotide, its complements, its homologs, and its variants and (2) for a polypeptide, the homologs of the polypeptide; the variants of the polypeptide and its homologs; and the fragments of the polynucleotide, its homologs, and its variants.
[0069] The term "virtual package" means that the components of a kit are associated by directions on one or more physical or virtual kit components instructing the user how to obtain the other components, e.g., in a bag containing one component and directions instructing the user to go to a website, contact a recorded message, view a visual message, or contact a caregiver or instructor to obtain instructions on how to use the kit.
[0070] The term "standard" means { 1 ) a control sample that contains tissue from a lean animal if a overweight animal is being tested or tissue from a overweight animal if a lean animal is being tested or (2) a control sample that contains tissue from a lean or overweight lest animal that has not been exposed to a test substance being examined in the corresponding lean or overweight animal to determine if the test substance causes differential yene expression, as appropriate for the context of its use.
[0071] The term "stringent conditions" means (1 ) hybridization in 50% (vol/vol) foπnamide with 0.1 % bovine serum albumin. 0.1% Ficotl, 0, 1% polyvinylpyrrolidone, 50 mM sodium phosphate buffer at pH 6.5 with 750 mM NaCI, 75 mM sodium citrate at 42T. (2) hybridization in 50% formamide, 5x SSC (0.75 M NaCI. 0.075 Vl sodium citrate). 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5x Denhardt's solution, sonicated salmon sperm DNA (50 μg/ral), 0.1 % SDS, and 10% dextran sulfate at 420C: with washes at 42T in 0.2x SSC and 0.1% SDS or washes with 0.015 M NaCl. 0.(M)15 M sodium citrate, 0.1 % Na?Sθ4 at 50''C or similar procedures employing similar low ionic strength and high temperature washing agetus and similar denaturing agents. [0072] The term "substance" means an element, compound, molecule, or a mix hire thereof or any other material that could potentially be useful for diagnosing, prognosing. or modulating the amount of adipose tissue on animals, including any drug, chemical entity, or biologic entity.
[0073] The term "'siRNΛ" means a polynucleotide that forms a double stranded RNA that reduces or inhibits expression of a gene when the siRNA is expressed in the same cell as the gene. The term encompasses double stranded RNA formed by complementary strands. The siRNA complementary portions that hybridi/e to form the double stranded molecule typically have substantial or complete identity. Typically, siRNA contains at least 15-50 nucleotides and the double stranded siRNA contains 15-50 base pairs, preferably 20-30 nucleotides and base pairs. [0074] The term "specifically bind" means a special and precise interaction between two molecules uhich is dependent upon their structure, particularly their molecular side groups. For exatnple. the intercalation of a regulatory protein into the major groove of a DNA molecule, the hydrogen bonding along the backbone between two single stranded nucleic acids, or the binding between an epitope of a protein and an agonist, antagonist, or antibody.
[007Sj The term "specifically hybridi/e" means an association between two single stranded polynucleotides of sufficiently complementary sequence to permit such hybridization under predetermined conditions generally used ui the art (sometimes termed "substantially complementary"). For example, the term may refer to hybridization of a polynucleotide probe with a substantially complementary sequence contained within a single stranded IWA or RNA molecule according to an aspect of the invention, to the substantial exclusion of hybridization of the polynucleotide probe with single stranded polynucleotides of non-complementary sequence. [0076] The term "variant" means ( D a polynucleotide sequence containing any substitution, variation, modification, replacement, detelkm. or addition of one or more nucleotides from or to a polynucleotide sequence and that has the same or substantially the same properties and performs the same or substantially the same function as the original sequence and (2) a polypeptide sequence cotuainύig any substitution, variation, modification, replacement, deletion, or addition of one or mote amino acids from or to a polypeptide sequence and that has the same or substantially the same properties and performs the same or substantially the same function as the original sequence. The term therefore includes single nucleotide polymorphisms (SNPs) and allelic variants and includes conservative and non- conservative amino acid substitutions in polypeptides. The term also encompasses chemical derivati/ation of a polynucleotide or polypeptide and substitution of nucleotides or amino acids with nucleotides or amino acids that do not occur naturally, as appropriate.
[0077] The invention is not limited to the particular methodology, protocols, and reagents described herein because they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention, As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise, e.g., reference to "a variant" includes a plurality of variants. Further, defined terms include variations of die terms used in the proper grammatical context, e.g., die term ".specifically binds" includes "specific binding" and other forms of the term. Similarly, the words "comprise", "comprises", and "comprising" are to be interpreted inclusively rather than exclusis ely.
[0078] Unless defined otherwise, all technical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of the invention. Although any compositions, methods, articles of manufacture, or other means or materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred compositions, methods, articles of manufacture, or other means or materials are described herein. [0079] AU patenis, patent applications, publications, and other references cited or referred to herein are incorporated herein by reference Io the extent allowed by law. The discussion of those references is intended merely to summarize ihe assertions made therein. No admission is made that any such patents, patent applications, publications or references, or any portion thereof, is relevant prior art for the present invention and the right to challenge the accuracy and pertinence of such patents, patent applications, publications, and other references is specifically reserved.
Modulation of Gene Protein Expression
[0080] In one embodiment, the present invention encompasses one or more genes or gene segments ("genes'" as defined herein) that are differentially expressed in the adipose tissue and/or lymphocytes of overweight animals compared to the adipose tissue and or lymphocytes of lean animals. The im ention is based upon the discovery of diffenrenhally expressed genes thai are represented by 445 polynucleotides in the adipose tissue of overw eight animals compared to the adipose tissue of lean animals and 1767 polynucleotides in the lymphocytes taken from overweight animals compared to lymphocytes taken from lean animals. The invention is further based upon the identification of 7 key genes involved in fatty acid metabolism that are diffenretially expressed between overweight and lean animals and are listed in (able 3. These key genes represent members of the pyruvate dehydrogenase kinase family, the carnitine palmitoyltransferase family and soluie carrier family 27 (fatty acid transporters) and genes associated with the elongation of long chain fatty acids, with the pyruvate dehedrogenase kinase family and the carnitine palmitoyltransferase family being the most important and in some instances rate limiting enzymes. The genes were identified by comparing the expression of genes in adipose tissue and lymphocytes taken from animals diagnosed as overweight with genes in adipose tissue and lymphocytes from animals diagnosed as lean using Affymelrix GeneChiptf technology. The polynucleotides are shown in "fable 1 , 2 and 3. The tables contain information the Λffymetrix Probe Identification Number (herein "APlN"). the p-value. the q-\alue, fold expression (fat, lean), the top BLAST annotation of the probe in question, the Accession Number of Highest BLAST Hit, the gene symbol and finally {he gene description is given in (he last column. A description of (he putative or actual gene can be in some instances obtained from the BLAS T' database using methods known to skilled artisans. Generally, the putative or actual gene function is determined by ( I) identifying the APfN for each gene that had 1.3 fold or greater gene expression in overweight animals compared to lean animals, (2) determining the nucleotide sequence of each such gene by inputting die APl1N into the publicly available Affymetrix database UmI correlates AlPN numbers with sequences, and (3) inputting the nucleotide sequence into the BLAST database provided by the National institutes of Health and determining the putative or actual gene function from the resulting sequence matches to homologous sequences in the database. [0081] The polynucleotides and genes are identified by measuring differences in gene expression from adipose tissue and the lymphocytes from canines diagnosed as overweight with gene expression in adipose tissue and the lymphocytes from canines diagnosed as lean. Changes in gene expression can be determined by any method known to skilled artisans. Generally, changes in gene expression are determined b> measuring transcription (determining the amount of mRNA produced by a gene) or measuring translation (determining the amount of protein produced by a gene). The amount of RNA or protein produced by a gene can be determined using any method known to skilled artisans for quantifying polynucleotides and proteins. Generally. RNA expression is determined using methods including but not limited to polymerase chain reaction (PCR) (including, without limitation, reverse transcription-PCR (RT-PCR) and quantitative real-time PCR (qPCR)), RNase protection. Northern blotting, and other hybridization methods. The RNA measured is typically in the form of mRNA or reverse transcribed mRNA or complimentary DNA (cDNA). Protein or polypeptide expression is determined using various colormetric. floureseense and spectroscopic assays and methods including but not limited to Western Blotting, ELISA, Multiple Reaction Monitoring. Reverse Phase and Antibody Arrays. In a preferred method, changes in gene expression are determined using Affymetrix Canine- 1 and Canine- 2 GeneChip^ available for purchase from AlTymelrix. Inc. and the instructions for using such chips to determine gene expression. [0082] Generally, differential gene expression in o\ erweight animals compared to lean animals is determined by measuring the expression of at least one gene. Preferably, the expression of two or more differentially expressed genes is measured to provide a gene expression pattern or gene expression profile. More preferably, the expression of a plurality of differentially expressed genes is measured.
[0083] The polynucleotides, genes, proteins encoded by the polynucleotides and genes, and the complements, homologs, variants, or fragments based upon the sequences are useful in a variety of prognostic and diagnostic assays relating to the amount of adipose tissue on an animal and are nseftil for screening test substances to determine if the substances are useful for modulating the amount of adipose tissue on an animal. Other uses will be apparent from the description of the invention contained herein.
[0084] In another aspect, the invention provides a combination comprising two or more polynucleotides that are differentially expressed in overweight animals compared to lean animals or two or more proteins produced by the expression of two or more polynucleotides that are differentially expressed m overweight animals compared to lean animals. In one embodiment, the combination comprises two or more polynucleotides or proteins expressed from polynucleotides selected from Tables 1 and 2 and preferably from table 3. Preferably, the combination comprises a plurality of polynucleotides or proteins expressed from polynucleotides identified in tables 1 and 2 and preferably from table 3, generally 10, 20. 50, H)O. 200, or more polynucleotides or proteins, us appropriate for a particular Group and use. When the combination comprises one or more fragments, the fragments can be of any si/e that retains the properties and function of the original polynucleotide or protein, preferably from 30"'», 6O0ZO. or 90% of the original. The polynucleotides and proteins can be from any animal, preferably canines and felines, most preferable canines.
[008Sj In anothei aspect, the invention pros ides a composition comprising two or more oligonucleotide or polynucleotide probes suitable for detecting the expression of genes differentially expressed in overweight animals compared to lean animals. In one embodiment, the probes comprise polynucleotides selected from tables I and 2 and preferably from table 3. In another, the probes comprise useful v ariations of such polynucleotides. The probes contain a sufficient number of nucleotides to specifically hybrid i/e substantially exclusively with appropriate complementary polynucleotides. In certain embodiments, the probes comprise at least 10, 35, 20, 25, or 30 nucleotides. In some embodiments, the probes contain more nucleotides and comprise at least 30. 50. 70. 90 or 100 nucleotides, or more. The probes may comprise full length functional genes of the present invention. Preferably, the composition comprises a plurality of polynucleotide probes suitable for detecting genes differentially expressed in overweight animals compared to lean animals, generally 10, 50, 200, 500, 1000, or 2000, or more probes. The polynucleotide probes are made or obtained using methods known to skilled artisans, e.g., in vitro synthesis from nucleotides, isolation and purification from natural sources, or enzymatic cleavage of the genes of the present invention.
[0086] In another aspect, the invention provides a device suitable for detecting the expression of a plurality of genes differentially expressed in overweight animals compared to lean animals. The device comprises a substrate having a plurality of the oligonucleotide or polynucleotide probes of the present inv ention affixed to the substrate at known locations. The device is essentially an immobilized version of the oligonucleotide or polynucleotide probes described herein. The device is useful for rapid and specific detection of genes and polynucleotides and their expression patterns and profiles. Typically, such probes are linked to a substrate or similar solid support and a sample containing one or more polynucleotides (e.g., a gene, a PCR product a ligase chain reaction (LCR) product, a DNA sequence that has been synthesized using amplification techniques, or a mixture thereof) is exposed to lhe probes such that the sample polynucleoιide(s) can hybridize to the probes. Either the probes, the sample polynucleotide(s). or both, are labeled, typically with a tluorophore or other tag such as sireptavidin. and detected using methods known to skilled artisans. If the sample polynucleotide(s) is labeled, hybridization may be detected by detecting bound fluorescence. If the probes are labeled, hybridization is typically detected by label quenching. If both die probe and the sample polynucieotide(s) are labeled, hybridization is typically detected by monitoring a color shift resulting from proximity of the two bound labels. A variety of labeling strategies and labels are known to skilled artisans, particularly for fluorescent labels. Preferably, the probes are immobilized, on substrates suitable for forming an
20 army (known by several names including DNA microarray. gene chip, biochip. DNA chip, and gene array) comparable to those known in the art. [0087] In another aspect, the invention provides a composition comprising two or more peptide or polypeptide probes suitable for detecting the expression of genes differentially expressed in overweight animals compared io lean animals. In one embodiment, the probes comprise peptides or polypeptides that specifically bind to proteins produced by the expression of one or more polynucleotides comprising sequences selected from tables I and 2. Iu another, the probes comprise peptides or polypeptides that specifically bind to proteins produced by expression of one or more polynucleotides comprising sequences selected from table 3.. In another, the probes comprise peptides or polypeptides ihat specifically bind to proteins produced by expression of one or more useful variations of such polypeptides. The probes contain a sufficient number of amino acids to specifically bind to the appropriate polypeptides. Preferably, the probes comprise at least 4, 10, 20, 40, or KO amino acids. In some embodiments, the probes contain more amino acids and comprise at least 100 or more amino acids. The probes may comprise full length functional proteins derh ed from the expression of full length functional genes identified by the present invention. Preferably, the invention provides a plurality of polypeptide probes suitable for detecting genes differentially expressed in overweight animals compared to lean animals, more preferably a collection of 10, 50, 100, 500, or 1000 or more of such probes. In one embodiment, the probes are antibodies, preferably monoclonal antibodies.
[0088] The polypeptide probes may be made according to conv entional methods, e.g., using the nucleotide sequence data provided for polynucleotides of the present invention and methods known in the art. Such methods include, but are not limited to, isolating polypeptide directly from cells, isolating or synthesizing DNA or RNA encoding the polypeptides and using the DNA or RNA to produce recombinant products, synthesizing the polypeptides chemically from individual amino acids, and producing polypeptide fragments by chemical cleavage of existing polypeptides.
[0089] In another aspect, the invention provides a device suitable for detecting the expression of a plurality of genes differentially expressed in overweight animals compared to lean animals. The device comprises a substrate having a plurality of the peptide or polypeptide probes of the present invention affixed to the substrate at known locations. The device i.s essentially an immobilized version of the peptide or polypeptide probes described herein. The device is useful for the rapid and specific detection of proteins and their expression patterns. Typically, such probes are linked to a substrate and a sample containing one or more proteins is exposed to the probes such that the sample proteins can hybridize to the probes, In certain embodiments, the probes, the sample proteins, or both, are labeled and detected, typically with a tluorophore or other agent known to skilled artisans. Generally, the same methods and instrumentation used for reading polynucleotide microarrays is applicable to protein arrays. Preferably, the probes are immobilized on a substrate suitable for forming an array.
[0090] Methods for determining the amount or concentration of protein in a sample are known to skilled artisans. Such methods include radioimmunoassays, competim e- binding assays, Western blot analysis, and ELlSA assays. For methods that use antibodies, polyclonal and monoclonal antibodies are suitable. Such antibodies may be immunologically specific for a protein, protein epitope, or protein fragment.
[0091] Some embodiments of the invention utilize antibodies for the detection and quantification of proteins produced by expression of the polynucleotides of the present invention. Although proteins may be detected by immunoprecipitation, affinity separation. Western blot analysis, protein arrays, and the like, a preferred method utilizes ELISA technology wherein the antibody is immobilized on a solid support and a target protein or peptide is exposed to the immobilized antibody. Either the probe, or the target, or both, can be labeled using known methods. [0092] In some embodiments, expression patterns or profiles of a plurality of genes differentially expressed in overweight animals compared to lean animals are observed utilizing an array of probes for detecting polynucleotides or polypeptides. In one embodiment, arrays of oligonucleotide or polynucleotide probes may be utilized, whereas another embodiment may utilize arrays of antibodies or other proteins that specifically bind to the differentially expressed gene products of the present invention. Such arrays may be commercially available or they may be custom made using methods known to skilled artisans, e.g., in-situ synthesis on a solid support or attachment of pre-synthesized probes to a solid support via micro-
22 printing techniques. In various embodiments, arrays of polynucleotides or polypeptides probes are custom made to specifically detecl transcripts or proteins produced by the differentially expressed genes of the present invention. [0093] In one embodiment, arrays of polynucleotide or polypeptide probes are custom made to specifically delect transcripts or proteins produced by two or more polynucleotides or genes identified in Table 2. These probes are designed to detect genes associated with lipid and glucose metabolism pathways in animals. In another embodiment, arrays of polynucleotide or polypeptide probes are custom made to specifically detect transcripts or proteins produced by two or more polynucleotides or genes identified in Table 3. These probes are designed to detect genes that are particularly relevant to overweight animals compared to lean animals.
[0094] In a further aspect, the invention prov ides a method for detecting the differential expression of one or more genes differentially expressed in o\ erweight animals compared to lean animals in a sample. The method comprises (a) hybridizing a combination comprising a plurality of polynucleotide probes that are differentially expressed in overw eight animals compared to lean animals with polynucleotides in the sample to form one or more hybridization complexes: (b) optionally, hybridizing a combination comprising a plurality of polynucleotide probes that are differentially expressed in overweight animals compared to lean animals with polynucleotides in a standard to form one or more hybridization complexes; (c) detecting the hybridization complexes from the sample and, optionally, the standard from step (b); and (d) comparing the hybridization complexes from the sample with the hybridization complexes from a standard, wherein a difference in the amount of hybridization complexes between the standard and sample indicate differential expression of genes differentially expressed in overweight animals compared to lean animals in the sample. In various embodiments, me plurality of polynucleotide probes are selected from Tables 1 and 2 and preferably from table 3. These polynucleotides are used to prepare probes that hybridize with sample polynucleotides to form hybridization complexes that are detected and compared with those of the standard. In some embodiments, the sample polynucleotides are amplified prior to hybridization. In some embodiments, the probes are bound to a substrate, preferably in an array.
23 [009SJ Step (b) and part of step (O are optional and are used if a relatively contemporaneous comparison of two or more test systems is to be conducted. However, in a preferred embodiment, the standard used for comparison is based upon data previously obtained using the method.
[0096] These probes are exposed to a sample to form hybridization complexes that are detected and compared with those of a standard. The differences between the hybridization complexes from the sample and standard indicate differential expression of polynucleotides and therefore genes differentially expressed in overweight animals compared to lean animals in the sample. In a preferred embodiment, probes are made to specifically detect polynucleotides or fragments thereof produced by one or more of the genes or gene fragments identified by the present invention. Methods for detecting hybridization complexes are know n to skilled artisans.
[0097] In one embodiment, the method further comprises exposing the animal or sample to a test substance before hybridization. Then, the comparison is indicative of whether the test substance altered the expression of genes differentially expressed in overweight animals compared to lean animals, particularly fat- associated genes, in the sample.
[0098] In another aspect, the invention provides a method for detecting the differential expression of genes differentially expressed in overweight animals compared to lean animals in a sample. The method comprises (a) reacting a combination comprising a plurality of polypeptide probes with proteins in the sample under conditions thai allow specific binding between the probes and the proteins to occur, wherein the proteins bound by the probes are differentially expressed in a overweight animal compared to a lean animal; (b) optionally, reacting a combination comprising a plurality of polypeptide probes with, proteins in a standard under conditions that allow specific binding between the probes and the proteins to occur, wherein the proteins bound by the probes are differentially expressed in a overweight animal compared to a lean animal, (c) detecting specific binding in the sample and. optional!) , the standard from step (b); and (d) comparing the specific binding in the sample with that of a standard, wherein differences between the specific binding in the standard and the sample indicate differential
24 expression of genes differentially expressed in overweight animals compared to lean animals in the sample.
[0099] In various embodiments, the plurality of polypeptide probes are probes that specifically bind to proteins produced by expression of one or more polynucleotides selected from Tables 1 aad 2 and preferably from table 3 and useful variations of such polynucleotides. These polynucleotides are used to prepare probes that specifically bind to proteins that are detected and compared with those of the standard. In some embodiments, the probes are bound to a substrate, preferably in an array . fn one embodiment, the probes are antibodies. [00100] Step (b) and part of step (c) are optional and are used if a relatively contemporaneous comparison of two or more test systems is to be conducted. However, in a preferred embodiment, the standard used for comparison is based upon data previously obtained using the method.
[001011 These probes are exposed to a sample to form specific binding that is detected and compared with those of a standard. The differences between the specific binding from the sample and standard indicate differential expression of proteins and therefore genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, in the sample. In a preferred embodiment, probes are made to specifically detect proteins or fragments thereof produced by one or more of the genes or gene fragments identified by the present invention.
[00102] In one embodiment, the method further comprises exposing the animal or sample to a test substance before reacting the polypeptides with the proteins. Then, the comparison is indicative of w hether the test substance altered the expression of genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, in the sample.
[00103] In another aspect, the method for detecting the expression of genes differentiall} expressed in overweight animals compared to lean animals in a sample is used to monicot an animal's progress when attempting to modulate the amount of adipose tissue on the animal in response to an adipose tissue modulation program. The method is performed at intervals, preferably set intervals, during the modulation program and the animal's progress monitored by comparing the results of the method at tw o or more points during the modulation program. A change in
25 expression of one or more of the genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, or i» the pattern of gene expression, or the lack of any change, resulting from the comparison indicates the effectiveness of the modulation program. For example, an adipose tissue modulation program designed io reduce die amount of adipose tissue on an animal could be monitored and shown to be effective if the amount of gene expression for genes differentially expressed in overweight animals compared to lean animals, particularly fat-associaied genes, declines oser time in response to the stimulus in the program. Similarly, a program to increase adipose tissue in a lean or overly lean animal should increase the expression profile for such genes. The modulation program can be any plan to modulate the amount of adipose tissue on the animal such as a diet, exercise, drug, or other similar program. [00104] In a further aspect, the invention provides a method for measuring the effect of a test substance on the expression profile of one or more genes differentially expressed in overweight animals compared to lean animals and a method for screening a lest substance to determine if it is likely to be useful for modulating the amount of adipose tissue on an animal. The methods comprise (a) determining a first expression profile by measuring the transcription or translation products of two or more polynucleotides selected from Tables 1 and 2 and preferably from table 3 or useful variations thereof in a test system in the absence of the test substance; (b) determining a second expression profile by measuring the transcription or translation products of two or more polynucleotides selected from Tables I and 2 and preferably from table 3 or useful variations thereof in a lest system in the presence of the test substance; and (c) comparing the first expression profile to the second expression profile.
{00105J A change in the second expression profile compared to the first expression profile of 1.3 fold or more indicates that the test substance effects the expression of genes differentially expressed in overweight animals compared to lean animals and that the test substance is likely to be useful for modulating the amount of adipose tissue on an animal. In a preferred embodiment, the genes differentially expressed in overweight animals compared to lean animals are key genes associated with fatty acid metabolism and the change is a 1.3 fold or more change in expression of at
26 least two genes between the first expression profile to die second expression profile. The invention also provides lhe substances identified using the method. [00106] In one embodiment, the polynucleotides are selected from Table 3 or useful variations thereof and the change is 1.3 fold or higher. [00107] In one embodiment, the test .system is an in vitro test system such as a tissue culture, cell extract, or cell line. In another, the test system is an in vivo test system, i.e.. an animal such as a canine. In other embodiments, the test system is an ex vivo tissue system or an in sihco system.
[00108] Test substances can be any substance that may have an effect on polynucleotides or genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes. Test substances include, but are not limited to. amino acids; proteins, peptides, polypeptides, nucleic acids, oligonucleotides, polynucleotides, small molecules, macromolecules, vitamins, minerals, simple sugars; complex sugars; polysaccharides; carbohydrates; medium- chain triglycerides (MCTs); triacylglycerides (TAGs); n-3 (omega-3 ) fatly acids including DIIA, EPA, ALA; n-6 (omega-6) fatty acids inciudmg LA, γ-li»oleuic acid (GLA) and ARA; SA. MA. conjugated linoleic acid (CLA); choline sources such as lecithin; fat-soluble vitamins including vitamin A and precursors thereof such as carotenoids {e.g., jVcarotene), vitamin D sources such as vitamin D; (ergocalciferol) and vitamin D,-, (cholecakiferol), vitamin E sources such as tocopherols {e g., α-tocopherol) and tocotrienols, and vitamin K sources such as vitamin K] (phylloquinone) and vitamin Ko (menadione); water-soluble v itamins including B vitamins such as riboflavin, niacin (including nicotinamide and nicotinic acid), pyridoxine, pantothenic acid, folic acid, biotin and cobalamin; and vitamin C (ascorbic acid); antioxidants, including some of the vitamins listed above, especially vitamins E and C; also bioflavonoids such as catechin, querceiin and theafiav in; quinones such as ubiquinone; carotenoids such as lycopeue and lycoxanthhr, resveratrol; and α-lipoie acid; L-carnitine; D-iimonene; glucosamine; S-adenosylmeιhionine; and chitosan. In a preferred embodiment, test substances are nutrients that may be added to food or consumed as a supplement. Examples include, but are not limited to, fatty acids such as omega-3 fatty acids (e.g.. DHA and EPA) and omega-6 fatty acids (e.g.. ARA), carnitine, methionine, vitamin C, vitamin E. and vitamin D.
27 [00109] In a preferred embodiment, the substances useful for affecting the expression of genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, may be identified using methods discloses in co-pending IiS Provisional Patent Application No. 60/657980, filed March 2, 2005, and any subsequent US or foreign patent application that claims priori iy thereto.
[00110] In a further embodiment, the invention encompasses a method for formulating a prognosis that an animal is likely to become overweight or developing a diagnosis that an animal is fat. The method comprises determining if one or more polynucleotides selected from tables i and 2 or useful variations thereof or one or more polypeptides that specifically bind to proteins produced by expression of one or more polynucleotides selected from tables K 2 or useful variations thereof are differentially expressed in the animal compared to one or mote lean animals. The animal is determined to be likely to become overweight or determined to be overweight if the comparison indicates that the polynucleotides are differentially expressed in the animal compared to the lean animals by a fold of 1.3 or more.
{001 H] In various embodiments, the prognosis or diagnosis is based upon the polynucleotides selected from Table 3. or useful variations of such polypeptides. [00112] The expression profile for lean animals used in the comparison can be obtained from one or more lean animals contemporaneously w'ln the expression profile for the animal being tested of from a database of lean animal expression profiles. Preferably, a database of expression profiles for lean animals accumulated over time is available for use as a reference.
JOOl 13J Determining if the polynucleotides or polypeptides are differentially expressed can be accomplished by detecting the polynucleotides or polypeptides using methods known Io skilled artisans, some of which are described herein. [00114] In another aspect, the invention provides a method for manipulating the genome or the expression of the genome of an animal, particularly a non-human animal. The method comprises disrupting the expression of one or more genes differentially expressed in overweight animals compared to lean animals, preferably using oligonucleotides or polynucleotides constructed using
28 polynucleotides selected from tables I and 2 and preferably from table 3 or useful variations (hereof
[00115] Methods of manipulating the genome are known to those of skilled in the an. Such methods include the production of transgenic and knockout animals and (lie disruption of transcription or translation. In one embodiment* one or more polynucleotides selected from tables 1 and 2 or useful variations thereof are used to prepare a construct useful to disrupt or "knock out" the corresponding endogenous gene in an animal. This method produces an animal having a null mutation for that gene locus, fn other embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-assoctated genes. The invention also provides an animal produced using the method. In various embodiments, the genome is manipulated using ihe one or more polynucleotides selected from Table 3. or useful variations of such sequences. The transgenic animals are preferably mammals, e.g., rodents such as mice and rats, but may be other mammal such as felines and canines.
[00116] Methods of manipulating the expression of genome are known to those of skilled in the art. Such methods include the use of antisense or siRNA molecules and using such molecules to disrupt the translation or transcription of the genome, fn one embodiment, one or more polynucleotides selected from tables I and 2 and preferably from table 3 or useful variations thereof are used to prepare antisense and similar DNA binding molecules that are useful for disrupting transcription or to prepare short <small) interfering RNAs (siRNA) useful for functionally disrupting translation. Briefly, gene expression is inhibited by anlisense molecules through binding to DMA and preventing transcription and a siRNA through RNA interference (RNAi) or post-iranscriptional gene silencing (PTGS). siRNA molecules target homologous mRNA molecules for destruction by cleaving the niRNA molecule within the region spanned by the siRNA molecule. Accordingly. siRNAs capable of taigeting and cleaving a mRNA transcribed from a fat- associated gene is used to decrease or eliminate expression of one or more of such genes. In other embodiments, antisense molecules capable of binding to DNA and siRNAs capable of targeting and cleaving mRNA transcribed from one or more
29 polynucleotides or genes selected from tables t and 2 and preferably from table 3 or useful variations thereof.
[00117] In another aspect, the invention provides a composition suitable for manipulating the genome of an animal. The composition comprises one or more substances that interfere with the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat- associated genes. Preferably, substances comprise oligonucleotides or polynucleotides that bind to one or more of the genes or their transcription products and interferes with their replication, transcription, or translation, most preferably oligonucleotides or polynucleotides constructed using polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof. In various embodiments, the substances comprise antisense molecules or siRNAs. [00118] In another embodiment, the invention encompasses a method for modulating the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, or modulating the amount of adipose tissue on an animal comprising administering to the animal a gene expression or tissue modulating amount of a composition comprising one or more of DHΛ, EPA. EPA and DHA, ALA, LA, ARA, SA and MA. In preferred embodiments the composition comprises, in milligrams per kilogram of body weight per day (mg/kg/day). DHA in amounts of from I to 30, preferably from 3 to 15: EPA in amounts of from 1 to 30, preferably from 3 to 15; EPA, DHA Combo (1.5: 1 ratio) in amounts of from 4/2 to 30/45, preferably from 9,6 to I S/12; ALA in amounts of from 10 to 100, preferably from 30 to 60; 1..A in amounts of from 30 to 600, preferably from 60 to 300: ARA in amounts of from 5 to 50, preferably from 15 to 30: SA in amounts of from 3 to 60, preferably from 6 to 30; MA in amounts of from 3 to 60, preferably from 6 to 30; and CLA (as a control) in amounts of from 6 to 120. preferably from 12 to 60. The composition can be administered to the animal in any manner or form suitable for the composition. Pteferably, the composition is administered to the animal orally in the form of a food composition or a supplement. The food composition may be of any form, e.g., a nutritionally balanced food composition known in the art such as dry foods, semi-moist foods, and v\et foods for animals, particularly companion animals such as feline and canine animals. Supplements include dosage forms such
30 as tablets, capsules, and similar forms. In a further aspect, the composition is administered in combination with one or more drugs or other substances that modulate the amount of adipose tissue on an animal. The drugs or substances include, but are not limited to. substances that suppress appetite, increase metabolism, or interfere with the absorption of specific nutrients, particularly from food. Examples include, but are not limited to. orhstat (blocks fat breakdown and absorption), anorexigenics such as dexedrine (suppresses appetite), anorectics such as fenfluramine and phentermine. and sibutramine, and phenylpropanolamine. [00119] In another aspect, the invention provides a composition suitable for modulating the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, or modulating the amount of adipose tissue on an animal. The composition comprises a gene expression or tissue modulating amount of one or more of DHA. EPA, EPA and DHA, ALA. LA, ARA, SA. MA. In various embodiments, the composition comprises, in mg kg/day. DHA in amounts .sufficient to administer to an animal from 1 to MK EPA in amounts sufficient to administer to an animal from t to 30; EPA DHA Combo (1.5:1 ratio) in amounts sufficient to administer to an animal from 4/2 to 30,45: ALA in amounts sufficient to administer to an animal from 10 to 100: LA in amounts sufficient to administer to an animal from 30 to 600; ARA in amounts sufficient to administer to an animal from 5 to 50; SA in amounts sufficient to administer to an animal from 3 to 60; MA in amounts sufficient to administer to an animal from 3 to 60 and CLA (as a control) i« amounts sufficient to administer to an animal from (•> to 120. Such substances are useful for modulating the amount of adipose tissue on an animal. . Preferably, the substances affect the expression of a plurality of such genes. In one embodiment, the composition further comprises one or more drugs or other substances that modulate the amount of adipose tissue on an animal.
[00120] In another embodiment, the invention encompasses methods for selecting an animal for inclusion in one or more groups or subgroups. The method comprises determining the expression profile of the animal for (a) polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof or (b) polypeptides each of which specifically binds to proteins produced by expression of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful v ariations thereof and assigning the animal to a group based upon the expression profile. The groups can be any useful groups, preferably those involved in a research experiment, trial, clinical trial, or other similar category. For example, the groups can be groups involv ed in a research experiment or clinical trial that requires a one or more coturol groups and one or more treatment groups, in, one embodiment, the control group comprises lean animals and the treatment group comprises overweight animals, or v ice versa in another. The expression profile for a plurality of animals can be determined and the animals assigned to the control group or treatment group based upon the results of the profile, i.e., animals with a differential expression of 1 ,3 fold or more compared to a standard are assigned to the overweight group and animals with a differential expression of 1.3 fold or less compared to a standard are assigned to the lean group. The method is particularly useful for assigning animals to a clinical trial when testing potential drugs or other substances for their ability to reduce the amount of adipose tissue on the animal. [00321 { In another aspect, the invention provides a computer system suitable for manipulating data relating to one or more genes differentially expressed in ov erweight animals compared to lean animals, particularly fat-associated genes. The system comprises a database containing information identifying the expression le\ el of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof and/or polypeptides that specifically bind to proteins produced by the expression of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof in lean animals and/or overweight animals and a user interface to interact with the database, particularly to input, manipulate, and rev iew the information for different animals or categories or animals, e.g., lean or overweight animals. In one embodiment, the database further contains information identifying the activity level of one or more polypeptides encoded by one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof, in another, the database further comprises sequence information for one or more of the polynucleotides selected from tables I and 2 and preferably from (able 3 or useful variations thereof. In other embodiments, the database contains additional information describing the putative description of the genes in one or more animal species. The computer system is any electronic device capable of containing and
32 manipulating the data and interacting with a user, e.g., a typical computer or an analytical instrument designed to facilitate using the present invention and oυtputiing the results relating to the status of an animal.
[00122] In another aspect, the invention provides a method for using a computer system or the present invention to present information identifying the expression profile of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes. The method comprises comparing the expression level of two or more polynucleotides or proteins expressed from polynucleotides selected from tables 1 and 2 and preferably from table 3 form a sample to the expression profile of the polynucleotides or proteins in the computer system.
[00123] In a further aspect, the present invention pres ides kits suitable for determining the differential expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat- associated genes, in a test system. The kits comprise in separate containers in a single package or in separate containers in a virtual package, as appropriate for the use and kit component, two or more probes suitable for detecting the expression of genes differentially expressed in overweight animals compared to lean animals, the probes comprising (a) polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof or <b) polypeptides that specifically bind to proteins produced by the expression of one or more polynucleotides selected from tables 1 and 2 and preferably from table 3 or useful variations thereof and at least one of (1 ) instructions for how to use the probes of the present invention: (2) reagents and equipment necessary to use the probes: (3) a composition suitable for modulating the expression of one or more genes differentially expressed in overweight animals compared to lean animals; (4) a composition suitable for disrupting the expression of one or more genes differentially expressed in overweight animals compared to lean animals; (5) a food composition suitable for modulating the amount of adipose tissue on an animal; and (6) one or more drugs or other substances that that modulate the amount of adipose tissue on an animal. In one preferred embodiment, the probes are bound to a substrate, preferably in an array.
Compositions of the Invention
33 [00124] The invention encompasses canine food compositions including 26 wt. % to 35 wt. % of crude protein on a dry matter basis, 7.5 wt. % to 8.5 wt. % of crude fat on a dry matter basis, 20 wt. % to 30 \vι. % of total dietary- fiber on a dry matter basis, and IO wt. % to 20 wt. % of etude fiber on a dry matter basis. {00125) The invention also encompasses feline food compositions including 30 wt. % to 3? wt. % of crude protein on a dry matter basis, 7.5 wt. % to 9 wt, % of crude fat on a dry matter basis. 30 wt, % to 35 w l. % of total dietary liber on a dry matter basis, and 20 wl. % to 25 wt. 1M) of crude fiber on a dry matter bask. [00126) In certain embodiments, the compositions of the invention can include an omega-3 polyunsaturated fatty acid content of at least 0.02% (or 0.05 % to 10%, or 0.1 % to 6%) by weight on a dry matter basis. In some embodiments, the oniega-3 polyunsaturated fatty acid is DHA. In other embodiments, the omega-3 polyunsaturated fatty acid is KPA. In still other embodiments, the omega-3 polyunsaturated fatty acid comprises a mixture of DHΛ and EPA. [00127] In other embodiments, the composition including the omega-3 polyunsaturated fatty acid is a food. Although both liquid and solid foods are provided, solid foods are typically advantageous. Foods include both dry foods and wet foods. Some of the non-polyunsaturated fatty acid components of the food, and useful proportions, include those listed below .
Canine Food Compositions
Figure imgf000035_0001
34 Dietary or 22 Wl. % to 28 \vt %. or 24 \vt % (o 26 %; or 20 wt. %, 20.5 Fiber wt. %. 21 \vt. %, 21.5 \\1. %. 22 \vt. %. 22.5 wt. %, 23 \vt. %, 23.5 wl. %, 24 wi %, 24.5 wt. %, 25 wt. %. 25.5 wt. 1H., 26 wl
%. 26 ...55 wwtt.. %, 27 wt. %. 27.5 wi. %, 28 wt. %, 28 5 w Λ'tt.. %%,, 29 wl. % L, 2299..55 wwtt.. % '.'7O
Crude H) \u. % to 20 wt. % of crude fiber on a dry matter basis, or 12 Fiber wt. % to 18 wt. %, or 14 wt. % to 16 %; or 10 wt. %. 10.5 wt. %, 1 1 wt. %. 1 1.5 wi %, 12 wt. %, 12.5 wt. %. 13 wt. %. 13.5 wl %. 14 wt. %, 14.5 wt. %. 15 wt. %. 1 5.5 wt. %, 16 wt. %. 16.5 wt. %. 17 wt. %, 17.5 wt. %, 18 wt. %. 18.5 wt. %. 19 wt. %, 10.5 wl. %
Feline Food Compositions
Component Proportion of the composition (% of dry weight of composition or pa its per million)
Protein 30 wt. % to hi wi. % of crude protein on a dry matter basis or 3 f wt. % to 36 wt. %. or 33% to 35%; or 30 wt. %, 30.5 wt. %, 31 wt. %, 31.5 wt. %, 32 wt %, 32.5 w t. %, 33 wl. %, 33.5 wt. %, 34 wi. %, 34.5 wt. %. 35 wt. %. 35.5 wl. %, 36 wt. 1M., 36.5 wt. %, 36 wt. %
Cnide Fat 7.5 wt. % to 9 wi. % of crude fat on a dry matter basis or 7.6 wt. %. 7 7 wt. %. 7.S wt. V 7» wt. %, 8.0 wl. %, 8.1 wt %, 8.2 wl. %. 8.3 wt. %. 8.4 wt. %, 8.5 vM. %. 8.6 wt. %, 8.7 w t. %. 8 8 wt %. 8.9 w i %. 9.0
Total 30 wt. % to 35 wt. % of total dietary fiber on a dry matter basis
Dietary or 31 wl. % to 34 wt. %, or 32 wl. % to 33 %; or 30 wt. %, 30.5
Fiber wi. %. 31 wt. %, 31.5 wt. %, 32 wt. %. 32.5 wt. %. 33 wt. %, 33.5 wt. %, 34 wt. %, 34.5 wt. %. 35 wt. %
Crude 20 wt. % to 25 wt. % of crude fiber on a dry matter basis, or 21 Fiber wt, % to 24 wt. %, or 22 wt. % to 23 %; or 20 wt. %. 20.5 wt. %,
21 wt. %. 21.5 wi %, 22 wl. %, 22.5 wt. Vo. 23 wt. %. 23.5 wt
35 Component Proportion of the composition (% of dry weight of composition or parts per million)
%. 24 wt. %. 24.5 wt. %, 25 wt. %
[00128] In one embodiment, the canine compositions of this invention include ingredients in an amount effective to enhance the animal's quality of hie. Such compositions generally comprise:
[00129] (a) 26 wt % to 35 wt. % of crude protein on a dry matter basis.
[001301 (b) 7.5 wt. % to 8.5 wt. % of crude fat on a dry matter basis,
[00131] (C) 20 wt. % to 30 wt. % of total dietary fiber on a dry matter basis, and
[00132 j (d) 10 w L % to 20 wt. % of crude fiber on a dry1 matter basis.
(00133) In another embodiment, the inv ention encompasses feline compositions that generally comprise:
[00134] (a) 30 wt. % to 37 wt. % of crude protein on a dry matter basis.
[00135] <b) 7.5 wt. % to 9 wt. % of crude fat on a dry matter basis.
[00136] (C) 30 wt. % to 35 wt, % of total dietary fiber on a dry matter basts, and
[00137] (d) 20 wt. % to 25 v, ι. % of crude fiber on a dry matter basis.
[00138] In another embodiment, the compositions generally comprise.
[00139] (a) at least one of the following:
(001401 (0 at least 0.05% (or 0.05% to 0.30%, or 0.1% to 0.30%, or 0.1% to
0.2%) DMA. and
[001411 <ii) at least 0,1% (or 0.1 % to 0.5%, or 0.2% to 0.5%. or 0.2% to 0.3%)
EPA.
[00142] (b) at least 15% (or 15% to 55%, or 30% to 55%, or 33% to 36%) protein.
(00143} (C) at least <>% (or 9% to 35%. or 18% to 35%, or 18% to 2'I1JO) fat, and
(00144) td) at least one of the following:
(001451 < 0 at least 250 If/kg (or 250 lU'kg to 15(H) IL' kg, or 500 IU kg to 1500 lU/kg. or 500 IL'/kg to 1 100 JL' Teg) vitamin R .
[00146] (xit) at least 50 ppm (or 50 ppm to 300 ppm, or 100 ppm to 3(K) ppm, or
100 ppm to 200 ppm) vitamin C.
|001471 (xiϋ)at least i 100 ppm (or 1 100 ppm to 3500 ppm, or 2300 ppm to 3500 ppm, or 2300 ppm to 2350 ppm) taurine, and
36 [0014Sf (xiv)at leasi 200 ppm (or 200 to 750 ppm, or 4(K) ppm to 750 ppm. or 400 to 525 ppm) carnitine, and
[00149] (XV) ai least 0.05% (or 0.05% to 0.6%, or 0.1 % to 0.6%. or 0.1% to 0.4%) cystine.
[00150] In another embodiment, (he compositions generally comprise:
[00151] (a) 0.02% (or 0.05 % Io 10%. or 0.1% to 6%) at least one omega-3 polyunsaturated fatty acid, and
[001521 (b) at least one of the following:
[00153] (\vi) 10% io 55% (or 1 S% to 30%, or 33% to 55% or 18% to 20% or 33% to 36%) protein,
{00154} (xvii) 7% to 35% (or 18% to 35%. or 7% to 24%, or 14% to 24%, or 14% to 16% or 18% (o 24%) fat,
[OO15S| (xviii) at least .05 (or 0.05 ppm to 75(K) ppm, or 250 to 3600, or 250 ppm to 1650 ppm, or 5 ppm to 225 ppm. or 0 05 ppm to 2.4 ppm) antioxidant, and
[001561 (xix)at least 1000 ppm (or 1000 ppm to 5000 ppm, 3300 ppm to 5000 ppm, or 2(K)O ppm to 3000 ppm, or 30(K) ppm to 4000 ppm) choline.
[00157] In another embodiment, the compositions generally comprise:
[00158] (a) at least one of the following:
[001591 (0 al leasi 0.02% (or 0.02% to 0.3%, or 0.05% to 0 3%, or 0 05% to
0.2%) DHA, and (ii) at least 0.1% (or 0.1% to 0.5%, or 0.2% Io 0.5%, or 0.2% to
0 3%) EPA.
[00160] (b) at least 9% (or V% to 30%. or 1 8% to 30%, or 18% to 20%) protein.
[00161] (c) ai least 7% (or 7% to 24%. or 14% to 24%, or f 4% to 16%) fat,
[00162] (d) at least one of the following:
(001631 <»> at least 250 If/kg (or 250 IU kg to 1500 IU kg, or 500 IU/kg to 1500
IU/kg, or 500 IU leg to 1000 IL'/kg) vitamin E .
[00164] <xx) at least 50 ppm (or 50 ppm to 500 ppm, or 100 ppm to 5(K) ppm, or
100 ppm to 301 ppm) \ itamin C,
[00165] (xxi)at least 600 ppm (oι 600 ppm to 2400 ppm, or 1260 ppm to 2400 ppm, or 1260 ppm to 1545 ppm) taurine, and
[00166] (xxii) at least 50 ppm (or 50 ppm to 200 ppm, or 100 to 160, or 100 to
155) hpoic acid. and
37 [001671 (Win) at least 50 ppm (oι 50 ppm to 500 ppm, or 200 ppm to 500 ppm, or
200 ppm to 350 ppm) carnitine,
[00168] (e) ai least 1000 ppra (or 1000 ppm Io 32W) ppm, or 2000 ppm to 3200 ppm, or 20(X) ppm to 2500 ppm) choline,
[00169] (0 ai least 50 ppm (oi 50 ppm to 150 ppm, o$ 100 ppm to 150 ppm, or
JOO ppm to 1 10 ppm) manganese, and
[0017Oj (g) at least 0 4% (or 0 4°.» to 2%, or 0.9% to 2%, or 0 9% to 1 2%)
Iv sine, and
[00171 j (h) at least 0 41M, to 1 5% methionine
[00172] In another embodiment, the compositions generally comprise.
[00173] (a) at least one of the following.
{00174) (i) at least 0.02% (or 0 02% to 0 31V or 005% to 0 3%, or 0.05% to
0.2%) DHA1 and
[001751 (it) at least 0.1% (ot 0 1 % to 0 5%, or 0 2% to 0.5%, or 0.2% to <>.3%)
EPA,
[00176] (b) at least <)% (or 9% to 30%. ot 18% to 30"O, or 18% to 20%) protein,
[00177] (C) at least ?% (or 7% to 24%. or 14% to 24%, or 14% to 16%) fat,
[00178] (d) at least one of the following:
100179) (i) at least 250 IL'/kg (ot 250 ID/kg to 1500 Hi/kg, or 500 IL'/kg to 1500
ΪU/kg, or 500 If/kg to 1000 IL' kg) utarrtin E .
[0018Oj (xxiv ) at least 50 ppm (or 50 ppm to 500 ppm, oi 100 ppm to 500 ppm, or
100 ppm to 301 ppm) vitamin C.
100181] (XXV ) at least 600 ppm {or 600 ppm to 24(M) ppm, or 12(>0 ppm to 2400 ppm, or 1260 ppm to 157^ ppm) taurine, and
[00182] (xxvi) at least 50 ppm (or 50 ppm to 200 ppm. or 100 to 160. or KM) to
155) Jφoic acid, and
[OOI83| (XXN n) at least 50 ppm (or 50 ppm to 500 ppm, or 200 ppm to 500 ppm, or
200 ppm to 350 ppm) carnitine,
100184] (e) at least 1000 ppm (or KK)O pptn Io 3200 ppm, oi 2000 ppm to 3200 ppm, or 2(H)O ppm to 2500 ppm) choline,
[00185] (t) at least 50 ppm (or 50 ppm to 150 ppm, or 100 ppm to 150 ppm, or
100 ppm to 1 10 ppm) manganese, and
W [00186} (g) at least 0 4",O (01 0 4S. to 2%, or (> «>% to 2%, or 0.9% to 1 2%)
Jy sine, and
[00187] (h) ai least 0 4"'« to 1 5% methionine
[00188] In another embodiment, the compositions generall> compnse"
{00189) (a) ai lettet one of the following.
[001901 (0 at least 0.05% (or 0 05"-« to 0 30%, or 0.1% to 0 30%, or 0 1 % to
0 2%) DHΛ. and
[001911 (π) at least 0.1% (ot 0.1 % to 0.5%. or 0.2%, to 0.5%, oi π.2% to 0.3%)
EPA,
[00192] (b) at least 15% (or 15% to 55%, or 30% to 55%, or 53% io 36%) ptotein.
{00193J (c) at least 9% (or 9% to 35V or 18% to 35%, oi 18% tυ 24"/«) fat.
[00194] <d) at least one of the following.
[001951 (D at least 250 1C kg (or 250 IU kg to 1500 lϋ/kg, oi 500 IU kg to 1500
IU kg. or 500 IL kg to 1 100 JU/kg) Mtanun E ,
[00196] (xx\iit) at least 50 ppro (or 5() ppm to 300 ppm. or HMt ppm lo 300 ppm, or 1 (K) ppm to 200 ppm) vitamin C,
[00197] (xx)x) at least 1 100 ppm (oi 1 100 ppm to 3500 ppm, or 2300 ppm to 3500 ppm, or 2300 ppm to 2350 ppm) taurine, and
[00198] (xxx) at least 200 ppm (or 200 to 750 ppm, or 400 ppm to 750 ppm, or 400 to 525 ppm) carnitine, and
[00199] (xxKi) at least 0 05% (oi 0 05% to 0.6%, oi 0 1% to 0 6%, or 0.1 % io
0 4%) cystine,
[00200] (e) at least 1600 ppm (or 1600 ppm to 5(K)O ppm, or 3300 ppm to 5(J(K) ppm, or 3300 ppm to 3400 ppm) choline,
[00201 ] (t) at least 50 ppm (oi 50 ppm to 150 ppm, oi 100 ppm to 150 ppm, oi
HX) ppm to 1 10 ppm) manganese, and
[002021 (g) at least 0 7% tot 0 7% to 3%, or I 4% to 3%, or 1 4% to 1 7%) lysine, and
[00203] (h) at least 0 4% to 1 5% methionine
Methods Of Treating Or Pmentmg Diseases And Disorders
V) [00204] The invention encompasses methods for treating or preventing diseases and disorders, including the administration of the compositions of the invention that are effective in modulating the expression and/or activity of proteins associated with obesity in animals both in vitro and in vivo. The inventors have surprisingly found that Uw compositions of the invention are effective in modulating proteins associated with obesity in animals. Without being limited by theory, it is believed that modulation of protein expression and/or activity associated with obesity in animals is useful in treating or preventing a disorder associated with abnormal blood glucose levels, weight gain, or fat depot levels. The invention further encompasses compositions and formulations that are useful in modulating protein activity in overweight and/or obese animals, lite invention also encompasses methods of modulating protein or gene activity including administering subject, preferably to a companion mammal in need of said treatment or prevention a therapeutically or prophy tactical Iy effective amount of a composition to modulate the activity of the protein or gene associate with obesity in the subject. In an illustrative embodiment, the agent for modulating lyn kinase activity is a compound of the invention.
[00205] In one embodiment, a composition of the invention is administered to a mammal, preferably a companion animal, with a cardiovascular disease, a dyslipidemia, a dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (i.e. , Syndrome X), a PPAR-associated disorder, septicemia, a thrombotic disorder, type Il diabetes, obesity, pancreatitis, hypertension, a renal disease, or inflammation.
[00206] In one embodiment, "treatment" or "treating" refers to an amelioration of a disease or disorder, or at least one discernible symptom thereof, preferably associated with obesity. In another embodiment, "treatment" or "treating" refers to an amelioration of at least one measurable physical parameter, not necessarily discernible by the animal. In yet another embodiment, "treatment" or "treating" refers to inhibiting the progression of a disease or disorder, either physically, e.g., stabilization of a discernible symptom, physiologically, e.g., stabilization of a physical parameter, or both. In yet another embodiment, "treatment" or "treating" refers to delaying the onset of a disease or disorder.
40 [00207] In certain embodiments, the compositions of the invention are administered to a patient, preferably a companion animal, as a preventative measure against such diseases. As used herein, "prevention'" or "preventing" refers to a reduction of the risk of acquiring a given disease or disorder. In a preferred mode of the embodiment, the compositions of the present invention are administered as a preventative measure to a patient, preferably a companion animal having a genetic predisposition to a cardios ascυiar disease, a dyslipidemia. a dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome {i.e.. Syndrome X), a PPAR- associated disorder, septicemia, a thrombotic disorder, type ϋ diabetes, obesity, pancreatitis, hypertension, a renal disease, or inflammation, [00208] In another illustrative mode of the embodiment, the compositions of the invention are administered as a preventative measure to a companion animal having a predisposition to a cardiovascular disease, a dyslipidemia, a dysiipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (/.<.' , Syndrome X), a PPAR- associated disorder, septicemia, a thrombotic disorder, type II diabetes, obesity, pancreatitis, hypertension, a renal disease, or inflammation. Accordingly, the compositions of the invention may be used for the prevention of one disease or disorder and concurrently treating another (e.g. , prevention of obesity while treating diaheies; prevention of inflammation while treating a cardiovascular disease).
Cardiovascular Diseases for Treatment or Prevention
[00209] The invention provides methods for the treatment or prevention of a cardiov ascular disease, comprising administering to a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle. In some embodiments, the cardiovascular disease is associated with abnormal/altered protein expression. As used herein, the term "cardiovascular diseases'" refers to diseases of the heart and circulatory system, These diseases are often associated with dislipoproteinemias and/or dyslipidemias. Cardiovascular diseases, which the compositions of the invention are useful for preventing or treating include, but are not limited to, arteriosclerosis; atherosclerosis; stroke; ischemia; endothelium dysfunctions, in particular those dysfunctions affecting blood vessel elasticity: peripheral vascular disease; coronary heart disease; myocardial infarction; cerebral infarction and restenosis. Dyslipidemias for Treatment or Prevention
[00210] The present invention provides methods for the treatment or prevention of a dyslipidemia comprising administering to a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle. In some embodiments, the dyslipidemia is associated with abnormal/altered lyn kinase activity and or expression. As used herein, the term "dyslipidemias" refers to disorders ihal lead to or are manifested by aberrant levels of circulating lipids. To (he extent that levels of lipids in the blood are too high, the compositions of the invention are administered to a companion animal to restore normal levels. Normal 1e\ els of lipids are reported in medical treatises known to those of skill in the art. For example, recommended blood leseis of LDL, HDL, free triglycerides and others parameters relating to lipid metabolism can be found at the web site of the American Heart Association and that of the National Cholesterol Education Program of the National Heart, Lung and Blood Institute. At the present time, the recommended level of HDL cholesterol in the blood is above 35 mg dL; the recommended level of LDL cholesterol in the blood is below 130 mg/dL; the recommended LDL:HDL cholesterol ratio in the blood is below 5: 1. ideally 3.5: 1 ; and the recommended level of free triglycerides in the blood is less than 200 mg/dL
[00211 j Dyslipidemias which the compositions of the invention are useful for preventing or treating include but are not limited to hyperlipidemia and low blood levels of high density lipoprotein (MDL) cholesterol. In certain embodiments, the hyperlipidemia for prevention or treatment by the compounds of the present invention is familial hypercholesterolemia; familial combined hyperlipidemia; reduced or deficient lipoprotein lipase levels or activity, including reductions or deficiencies resulting from lipoprotein lipase mutations; hypertriglyceridemia; hypercholesterolemia; high blood levels of ketone bodies (c.χ., β-OH butyric acid); high blood levels of Lp(a) cholesterol; high blood levels of low density lipoprotein (LDL) cholesterol; high blood levels of very low density lipoprotein (VLDL) cholesterol and high blood levels of non-esteπfied fatty acids. {002121 The present invention further provides methods for altering lipid metabolism in a patient, for example, reducing LDL in the blood of a companion
42 animal, reducing free triglycerides in ihe blood of a patient, increasing {he ratio of HDL to LDL in (he blood of a patient, and inhibiting saponified and or non- saponified fatty acid synthesis, said methods comprising administering to (he patient a composition comprising a compound of the invention in an amount effective alter lipid metabolism.
Dislipoproteinemias for Treatment or Prevention
[00213] The invention prov ides methods for the treatment or prevention of a dysiipoproteinemia comprising administering to a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle. As used herein, the term "dyslipoproteinemias" refers to disorders that lead to or are manifested by aberrant levels of circulating lipoproteins. To the extent that levels of lipoproteins in the blood are (oo high, the compositions of the invention are administered to a patient to restore normal levels. Conversely, to the extent that levels of lipoproteins in the blood are loo low. the compositions of the invention are administered Io a patient to restore normal levels. Normal levels of lipoproteins are reported in medical treatises known to those of skill in the art.
{00214} Dyslipoproieinemias. which the compositions of the present invention are useful for preventing or treating include, but are not limited to, high blood levels of LDL; high blood levels of apolipoprotein B (apo B): high blood levels of Lp(a); high blood levels of apo(a); high blood levels of VLDL; low blood levels of HDL; reduced or deficient lipoprotein lipase levels or activity, including reductions or deficiencies resulting from lipoprotein lipase mutations; hypoalphalipoproteinemia; lipoprotein abnormalities associated w ith diabetes; lipoprotein abnormalities associated with type 11 diabetes, obesity; lipoprotein abnormalities associated w ith Alzheimer's Disease; and familial combined hyperlipidemia.
Glucose Metabolism Disorders for Treatment or Prevention [00215] The invention prov ides methods for the treatment or prevention of a glucose metabolism disorder, comprising administering Io a companion animal a therapeutically effective amount of a composition of the invention and a pharmaceutically acceptable vehicle. As used herein, the term "glucose
43 metabolism disorders" refers to disorders that lead io or are manifested by aberrant glucose storage and/or tin Ii /at ton. To the extent that indicia of glucose metabolism (λtf., blood insulin, blood glucose) arc too high, the compositions of the invention axe administered to a patient to restore normal levels Conversely, to the extent that indicia of glucose metabolism are too low. the compositions of the invention are administered to a patient to restore normal levels. Normal indicia of glucose metabolism are reported in medical treatises know n to those of skill in the art, In some embodiments, the glucose metabolism disorder is associated with abnormal/altered lyn kinase activity and or expression.
[00216] Glucose metabolism disorders which the compositions of the present invention are useful for preventing or treating include but ate not limited to impaired glucose tolerance; insulin resistance; insulin resistance related breast, colon or prostate cancer; diabetes, including but not limited to non-insulin dependent diabetes meUitus (NlDDM), insulin dependent diabetes mellitus (IDDM). gestational diabetes mellitus (GDM), and maturity onset diabetes of the young (MODY); pancreatitis; hypertension; polycystic ovarian disease; and high levels of blood insulin and or glucose.
[00217] The invention further provides methods for altering glucose metabolism in a patient, for example to increase insulin sensitivity and/or oxygen consumption of a companion animal, said methods comprising administering to the companion animal a composition comprising a compound of the invention in an amount effective to alter glucose metabolism.
Treatment or Prevention of Metabolic Syndrome
[00218] As used herein, "treatment or prevention of Syndrome X or Metabolic Syndrome" encompasses treatment or prevention of a symptom associated with metabolic syndrome including, but not limited to, impaired glucose tolerance, hypei tension and dyslipidemia and/or dislipoproteinemia. In some embodiments, the metabolic syndrome is associated with abnormal/altered fyu kinase activity and/or expression
[00219] Metabolic syndrome is characterized by a group of metabolic risk factors in a person. Risk factors that are associated with metabolic syndrome that can be
44 treated or prevented by administering a composition comprising a compound of the imemiott include, but are not limited to, central obesity (Le,, excessive fat tissue in and around the abdomen); atherogenic dyslipidemia (blood fat disorders - mainly high triglycerides and low HDL cholesterol - that foster plaque buildups in artery- walls); raised blood pressure ( 130 85 mmMg or higher); insulin resistance or glucose intolerance (the body can't properly use insulin or blood sugar): prothrombotic state (e.g.. high fibrinogen or plasminogen activator inhibitor |- I { in the blood); and a proinflammatory stale (c.#., elevated high-sensitivity C-reactive protein in the blood).
|OO22O] The underlying causes of this syndrome are overweight obesity, physical inactivity and genetic factors, companion animal with metabolic syndrome are at increased risk of coronary heart disease, other diseases related to plaque buildups in artery walls {e.g. , stroke and peripheral vascular disease) and type 2 diabetes. [002211 Metabolic syndrome is closely associated with a generalized metabolic disorder called insulin resistance, in which the body catft use insulin efficiently. This is why the metabolic syndrome is also called (he insulin resistance syndrome. [00222] Some companion animal are genetically predisposed (o insulin resistance. Acquired factors, such as excess body fat and physical inactivity, can elicit insulin resistance and the metabolic syndrome in these people. Most companion animal with insulin resistance have central obesity. The biologic mechanisms at the molecular level between insulin resistance and metabolic risk factors aren't fully understood and appear to be complex.
[00223] The compositions of the invention are therefore useful hi Heating or preventing metabolic syndrome and disorders and risk factors associated with metabolic syndrome.
Treatment or Prevention Type II Diabetes
[00224] As used herein, "treatment or prevention of type Il diabetes" encompasses treatment or prevention of a complication associated with type II diabetes including, but not limited to, retinopathy (/.t\, blindness); neuropathy (r.c, nerve damage) which leads to foot ulcers, gangrene, and amputations: kidney damage, which leads to dialysis: and cardiovascular disease. In some embodiments, the type
45 U diabetes is associated with abnormal altered lyn kinase activity and'or expression.
[00225] Type 11 diabetes is associated with obesity and with aging. It is a lifestyle- dependent disease, and has a strong genetic component (concordance in twins is 80- 90%). The problem seems not so much in insulin production, but that when the insulin reaches its target cells, it doesn't work correctly. Most Type II diabetes patients initially have high insulin levels along with high blood sugar. However, since sugar signals the pancreas to release insulin, Type II diabetics eventually become resistant to that signal and the endocrine-pancreas soon will not make enough insulin. These companion animals end up managing the disease with insulin and they n^ά much higher doses because they are resistant to it. {00226) When a companion animal takes in a high load of sugar, the sugar stimulates the pancreas to release insulin. The targets for insulin are muscle, fat, and us er cells. These cells have insulin receptor sites on the outside of the ceil membrane. For most companion animals, when insulin has bound to the receptors, a cascade of events begins, which leads to sugar being transported from the blood into the interior of the cell. In Type Il diabetics, even when insulin is present on the cell membrane, the process doesn't work. The glucose is never taken tip into the cell and remains in the bloodstream.
[00227] The liver is responsible for glucose production and insulin is the regulator)' agent of production. A high blood sugar content causes the pancreas to release insulin, and the insulin should signal the liver to stop making sugars. But. in diabetics, there's resistance to that signal and the liver keeps producing glucose. Hyperglycemia leads to glucose toxicity.
[00228] It is not high blood sugar that is the disease process of diabetes, but complications from the high blood sugar. A major problem faced by doctors is that some people with high blood sugar feel fine; it's hard to treat diseases that are asymptomatic since most people don't want to take a pill for something that they don't feel bad about. The compositions comprising a compound of the invention are therefore useful in treating or preventing type II diabetes or complications arising from type 11 diabetes and disorders and risk factors associated with metabolic syndrome. Complications of diabetes include, but are not limited to, diabetic neuropathy, diabetic retinopathy, erectile dysfunction, and kidney disease
46 and (lie compounds of the invention are useful in treating or preventing ώe.se complications.
Treatment or Prevention of Obesity
{00229) As used herein, "treatment or prevention of obesity" encompasses treatment or prevention of a complication associated with obesity. Complications of obesity include, but are not limited to. hypercholesterolemia, hypertension, dyslipidemia (for example, high total cholesterol or high levels of triglycerides), type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea and respiratory problems, and some cancers (endometrial, breast, and colon). In some embodiments, the obesity is associated with abnormal altered lyn kinase activity and/or expression
Other Diseases for Treatment or Prevention
[00230] The present invention provides methods for the treatment or prevention of septicemia, thrombotic disorders, pancreatitis, hypertension, inflammation, and impotence, comprising administering to a patient a therapeutically effective amount of a composition comprising a compound of the invention and a pharmaceutically acceptable vehicle. In some embodiments, these disorders are associated with abnormal altered lyn kinase activity and/or expression
[00231] As used herein, "treatment or prevention of septicemia" encompasses treatment or prevention of septic .shock.
[00232] As used herein, "treatment or prevention of thrombotic disorders" encompasses treatment or prevention of high blood levels ot fibrinogen and promotion of fibrinolysis.
[00233] In addition to treating or preventing obesity, the compositions of the invention can be administered to an individual to promote weight reduction of the individual.
Kits of the Inv ention
[00234] When the kit comprises a v trtual package, the kit is limited to instructions in a virtual environment in combination with one or more physical kit components. In one embodiment, the kit contains probes and or other physical components and
47 the instructions for using the probes and other components are available via the internet. The kit may contain additional ilems such as a device for mixing samples, probes, and reagents and device for using the kit, e.g., test tubes or mixing utensils. {00235} In another aspect, the present invention provides a means for communicating information or instructions for one or more of (1 ) using the polynucleotides of the present invention for delecting the expression of genes differentially expressed in overweight animals compared to lean animals in a sample. (2) using the polynucleotides of the present invention for measuring the effect of a test substance on the expression of one or more genes differentially expressed in overweight animals compared to lean animals, O) using the polynucleotides of the present invention for screening a lest substance to determine if it is likely to be useful for modulating the amount of adipose tissue on an animal, [4] using the polynucleotides of the present invention for formulating a prognosis thai an animal is likely to become overweight or developing a diagnosis that an animal is tat, (5) using the polynucleotides of the present invention for manipulating the genome of a non-human animal or the expression of the genome of an animal. (6) using the polynucleotides of the present invention for modulating the expression of one or more genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, or modulating the amount of adipose tissue on an animal. (7) using the polynucleotides of the present invention for selecting an animal for inclusion in one or more groups. (8) using the polynucleotides of the present invention for using computer system to manipulate data relating to genes differentially expressed in overweight animals compared to lean animals, particularly fat-associated genes, (9) administering substances of the present invention to an animal, alone or in combination with the other elements of the present invention. ( 10) using the substances of die present invention for modulating the amount of adipose tissue on an animal, ( 1 1 ) using the computer system of the present invention, (12) using the kits of the present invention, and (13) instructions for using the methods and compositions of the present invention with one or more drugs or other substances that that modulate the amount of adipose tissue on an animal. The means comprises a document, digital storage media, optical storage media, audio presentation, or visual display containing the information or instructions. In certain embodiments, the communication means is a
48 displayed web she, x i.sual display, kiosk, brochure, product label, package insert, advertisement, handout, public announcement, aυdiolape, \ tdeotape, DVD, CD- ROM, computer readable chip, computer readable card, computer readable disk, computer memory , or combination thereof containing such information or instructions. Useful information includes one or more of < 1) methods for promoting the health and wellness of animals and t,2) contact information for the animal's caregiv ers to use if they hase a question the invention and its use. Useful instructions include techniques for using the probes, instructions for performing a gene expression assa>. and administration amounts and frequency for the substances. T he communication means is useful for instructing on the benefits of using the present invention.
[00236] Disclosed herein are typical illustrative embodiments of the invention and, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation as many modifications and variation of the invention are possible in light of the teachings contained herein. The invention can be further illustrated by the following examples, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the invention unless otherwise specifically indicated.
EXAMPLES
Materials and Methods
Isolation of Ribonucleic Acid (RNA) from Tissue
[00237] Tissue samples that have been collected, fro/en in liquid nitrogen, and thawed are homogenized and processed using a TRl/ok^1 RNA extraction method to produce good quality RNA which is then subjected to further genomic analysis. [00238] Mateπals. ice, liquid nitrogen, frozen canine or feline tissue, TRIzok* lysis reagent, chloroform minimum 99%, isopropyl alcohol. 70% ethanol (prepared with ethanol, absolute and deioni/ed. RNase-free water), RNase Zap R\ deioni/ed water, RNA Storage Solution^1, from Ambion.
49 [00239] Equipment; L'ltra-Turrax T25 Power Homogeni/er, Beckman Coulter Allegra 25R Centrifuge, Eppendorf Centrifuge, forceps, scalpel, hard cutting surface, i.e. cutting board, 1.5mL DNase and RNase free/sterile microcentrifuge tubes, 5OmL DNase and RNase free/steπle disposable polypropylene tubes, P IOOO, P20<). P20, P iO and Ϋ2 Raitπn Pipetman pipettes, filter pipette lips for PlOOO, P200, P20. PK) and P2 pipettes, DNase and RNase free- sterile, and lint free wipes. [00240] Preparations: Prepare 5OmL polypropv lene tubes with 4mL TRI/oiA' tone tube for each tissue selected for RNA isolation).
[00241] Tissue Homogeni/ation: Fill a container capable of holding liquid nitrogen with 3-4 scoops of liquid nitrogen Place a piece of fro/en tissue immediately into the aforementioned container (the tissue should be the si/e of a pea) and place the tissue into the appropriate labeled 5OmL polypropylene tube (that already contains 4mL TRl/ol>*C). Immediately begin homogenizaUon using the Ultra-Turraκ T25 Power Homogeni/er. Homogenize on the highest setting (f>) for 10-15 seconds Cool the sample on ice for another 10- 15 seconds and then repeat. Continue until the tissue is fully homogenized and the solution is cloudy . Upon complete homogeni/ation. cap the 5OmL tube and return Io the ice. Incubate the homogenized tissues at room temperature for 5 minutes before proceeding with the isolation procedure.
[00242] RNA Isolation: The procedures given in the Invitrogen instructions provided with the TRI/olΛ reagent are generally followed. Separate the homogenized sample into four I mL aliquots in four l .5πiL microcentrifuge tubes. Add 20OuL of chloroform to each ImL aliquot. Cap the tubes, vortex for 15 seconds and then shake up and down. The result should be a pink milky liquid. Incubate the tubes at room temperature for 2-3 minutes. Centrifuge the tubes for 15 minutes at 14,000 rpm and 40C. Transfer the aqueous phase (top layer) to a sterile L5mL microcentrifuge tube. The typical \oinme of the aqueous phase which should be transferred to the new tube is 50OuL. Be sure not to transfer any of the intermediate or lower phase. Precipitate the RNA fiom solution by adding 50OuL of lsopropyl Alcohol to each microcentrifuge tube containing the aqueous layer. Shake the tubes up and down for at least 20 seconds, incubate the samples at room temperature for 10 minutes. Centrifuge die samples for 10 minutes, 14,000 rpm at 4T. Remove the supernatant carefully by aspirating off the liquid being we not to
50 lose the pellet. Add ImL of 70% elhanol to wash the pellet. Dislodge the pellet by Oicking (he tube (or tapping the tube on the bench top) and shake to mix. Centrifuge for 5 minutes. 8,200 rpm at 4'JC. Remove (he supernatant carefully by aspirating off the liquid being sure not to lose the pellet. Using a lint free wipe carefully soak up excess ethanoi to make sure the pellet is dry- Resuspend each pellet into 3OuL of RNA Storage Solution. Mix gently by pipetting until the RNA goes back into solution and then store at -80ΛC. It may be necessary- to vortex the sample for a few seconds at a low speed to facilitate the resυspensioπ. of the RNA. If this is necessary', spin down the samples, using the microcentrifuge, prior to freezing.
J00243J RKA Cleaning: The procedures given in the RNeasytf' Mint Handbook are followed.
RISA Isolation from Cells Cultured Ui OptiCeil Chambers Using the RNeasy
Mini Kit.
[00244] Cells cultured from mammalian cell lines are used to isolate good quality
RNA which is then used for future downstream genomic analysis. All work related to the culruring of the cells is to be done υnder strict aseptic conditions.
100245} Reagents: 1OX PBS, deioni/ed M2O, absolute ethanoi, RNA Storage
Solution, β-Mercaptoethanol. RNase Zapκ\ Buffer RLT, and Buffer RW l and
Buffer RPE (provided in the RNeasy Mini Kit)
[00246] Equipment/Materials: RNeasy Mini Kit, QIAshredder spin columns,
OptiCeil knife, 2OmI. sterile syringe, OptiCeil tips. Cell scraper, PHM)O Pipetinan pipette, Rninin. P200 Pipetman pipette. Rainin, 100- U)OuL filtered pipette tips, 1 -
20OuL filtered pipette tips, sterile transfer pipettes. 55mL sterile solution basin, l.5mL sterile microcentrifuge tubes, and Eppendorf Microcentrifuge.
[00247] Solutions: Buffer RLT (stock provided in RNeasy Mini Kit); -Add K)OuL of β-Mercaptoethaπol per 1 OmL of Buffer RLT prior to beginning protocol. 70%
Ethanoi; Make 5OmL of 70% ethanαl b> adding 35m L absolute ethanoi to l 5mL deioro/ed, RNase-free svater. IX PBS: RNase- free water. Filter (he solution using a
.22um filter.
[00248] Procedure: Removing Cells from the OptiCeil Chamber (proceed one
OpJiCeIl at a time). Check the cells under a microscope to ensure that the cells are alive before isolating RNA. Remove and discard the cell culture medium. Using the OptiCeii knife cui away the top membrane exposing the cells on the lower membrane. Wash the membrane to which the cells are attached three times with IX PBS. Pipette 60OuL of the Buffer RLT solution {containing β-Mercaptoethanol) onto the center of the membrane to which the cells are attached. Using the ceil scraper, gently spread the Buffer RLT over the entire surface of the membrane, and then collect the liquid in one comer. Pipette off the entire volume of Buffer RLT and place into a QlAshredder spin column,
[00249] RNA Isolation: Centrifuge the QlAshredder spin columns at 14,000 rpm for 2 minutes. Discard the spin column but keep the collection tube and its contents. Add 6ihH.lL of 70% ethanoi to the collection Cube and mix well by pipetting (the total volume now :: l .2mL). Transfer 60OuL of the ceil lysate to an RNeasy mini column and centrifuge for 15 seconds at 14,000 rpm. Discard the How through but keep the collection tube and the spin column. Transfer the remaining volume of ceil iysate <~6(K)uL) to the spin column and repeat the centrifugal ion. Discard the flow through but keep the collection tube and the spin column Add 7(HHtL Buffer RWt to the spin column. Centrifuge for 15 seconds at 14,0(X) rpm to wash the column. Discard the flow through and the collection tube. Transfer the spin column to a new 2mL collection tube and add 50OuL Buffer RPE to the column. Centrifuge for 15 seconds at 14.000 rpm. Discard the flow through, keep the collection tube, column. Add another 50OuL Buffer RPE to the column. Centrifuge for 2 minutes at 14.000 rpm. Transfer the .spin column to a l .5nιL collection tube. Add 3OuL of RNA Storage Solution directly to the silica gel membrane and centrifuge for 1 minute at 14,000 rpm to elute the RNA. Store the final RNA at -70X.
RNA 6000 N a no Assay
[00250] Using the Agilent 2100 Bioanaly/er and the RNA WK)O Nano Assay, anal>/e RNA isolated from cultured mammalian ceils, lymphocytes or tissues for quality.
[00251] Reagents: RNA 6000 Nano gel matrix, RNA 6(X)O Nano dye concentrate,
RNA 6000 Nano Marker, (ail of the above reagents are contained in the RNA 6000
Nano Assay kit, Agilent). RNA 6000 ladder, RKase Zap . and RNase-free water, from Ambion.
52 [OO2S2J Equipment Other Materials: Agilent Chip Priming Station, Agilent, RNA 6000 chip. Agilent, electrode cleaners, P2, P lO, P200. and PiOOO Rainin Pipetman pipettes, sterile, DNase-'RNase free filtered pipette tips, 1.5mL microcentrifuge tubes, sterile, vortex, IKA vortex mixer, microcentrifuge, and heating block, {00253) Procedure; The procedure is given in the Reagent Kit Guide. RNA 6000 Nano Assay, Edition November 2003, by Agilent Technologies. The procedures are followed as given in the Guide, with the following modifications: Preparing the Gel. pg. 17- rather than separating the filtered gel into aliquots of 65uL each, keep the stock filtered gel in the original microcentrifuge tube and aliquot the 65υl. as needed. Loading the RNA 6000 Nano Marker, pg. 22- add HtL of RNase-lree wafer (instead of RNA (»000 Nano Marker) to each sample well that will not contain sample. Not only will flu's conserve the amount of Marker used but also serves as a negative control to see that none of the reagents are contaminated, including the RNase-free water. Loading the Ladder and Samples, pg. 23- heat denature the samples and RNA 6000 Ladder for an additional 30 seconds (total of 2.5 minutes) at 710C. Starting the Chip Run, pg. 26- choose the "Eukaryole Total RNA Nano" option from the assay menu. Affymetrix Geuechip Expression Analysis
{00254J Gene expression is analyzed using Asymetrix Canine 1 and Canine 2 GeneChip^" Arrays are available commercially from Affymetrix, Inc., Santa Clara, CA 95051. Total RNA is reverse transcribed into cDNA. The cDNA is used to generate cRNA which is fragmented and used as probes for GeneChip hybridization. The gene chip is washed and the hybridization signal is measured with an Affymetrix laser scanner. The hybridization data is then validated and normalized for further analysis.
[00255] Materials: Affymetrix provides most of the reagents and kit. Other reagents listed in the Aflymerrix Manual but not supplied in the kit may be obtained separately (refer to GeneChip Expression Analysis Technical Manual (701021 Rev.4) for details), RNase Zap-fc and deioni/.ed water. [00256] Equipment: Eppendorf microcentrifuge, 1.5mL DNase and RNase free sterile microcentrifuge tubes, 5OmL DNase and RNase free/sterile disposable polypropylene tubes, PlOOO, P200. P20, PlO and P2 Rainin Pipetman pipettes.
53 Filter pipette lips lor PlOOO, P200, P20, P IO and P2 pipettes. DNase and RNa.se free sterile, and Peltier Thermal Cycler PTC-200.
[00257] Procedure: follow all procedures exactly as described in GeneChip Expression Analysis Technical Manual (Affymetrix Copyright 1999-2003). Use 5 microgram of total RNA for the first strand cDNA synthesis. Use either Peltier Thermal C) cler PTC-200 or heat block for temperature control on reactions and probe denaturing. The quality control is performed using RKA NanoDrop chips with BioAnalyer 2100. Use 100 Formal (Midi Array) for the canine geuechip.
Example 1
Determining Differential Gene Expression between Adipose Tissue Samples from Overweight and Lean Animals
[00258] Adipose tissue samples are obtained from 18 (3 lean and 15 fat) or lymphocytes obtained from 44 (12 lean and 32 fat) canine animals diagnosed as either v'fat" or ''lean" using conventional methods. The "fatness" or '"leanness" of an animal is determined based on measurements by DEXA using conventional methods or based on a 5 point body condition scoring system. For example, an animal is considered lean if it has a body condition score of 2 or 2.5 and or a DEXA total body fat percentage of 27% or less. An animal is considered to be overweight if it has a body condition score of 4 or higher and a total body fat percentage of 30% or higher. All solid tissue samples were snap fro/en in liquid nitrogen immediately after removal ftom the animal. The lymphocytes were isolated using BD VactuainerxR CPT tM Cell Preparation Tube according to manufactuerers instructions and were also snap fro/en until needed. The samples were alt analyzed using Affymetrix Canine-2 GetteChips* according to manufacturers recommendations in order to determine which genes are differentiall} expressed in overweight animals compared to lean animals.
The data was analyzed using Partek* GS (Partek !ue . St. Charles, MO) for Gene Expression Data software (Parlek Incorporated, 12?47 Olive Blvd., Suite 205, St. Loins, Missouri 63141 , U.S.A. http: AYww.paiiek.com, paitekgs geneexpression ). The Robust Munich ip Average (RMA) algorithm ( Rafael. A. Iri/arry, Benjamin
54 M. Bolstad, Francois Collin. Leslie M Cope, Bridget Hobbs and Terence P. Speed (2003 ). Summaries of Affymetrix GeneChip probe level data Xutieic Acid* Research 31 (4V.el5 ) was used for background adjustment, normalization, and probe-level summarization of the GeneChip* samples. The ANOVA analysis was performed io find significant differentially expressed genes between any two groups with a minimal FDR control at O. I (or p-\alue of O. J or 0.05 if power was not sufficient to apply FDR) and a fold change of 1.3 in each direction. Our empirical studies have revealed thai the Canine-2 GeneChips* have an associated background noise level of 1 .3 fold. Therefore, all analyses presented in this report employed a -*/- 1.3 fold cut-off. Furthermore, the false discovery rate threshold of [1 ] (means that 10% of observations are due to chance) was chosen as the minimum level of acceptable statistical significance for studies containing a minimum of 12 animals per group. Studies with smaller numbers of animals do not have enough power to allow for the proper application of the FDR. Results are provided in the tables below.
55 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Fat vs Lean (Adipose Tissue Gene Expression Comparison) allgenelist FC cutoff: 1.3; P-vat cutofff: 0.1; Q-val cutoff: 1
#S3mpies in group- 1 (ADP FAT): 15 group-2 (LEAN ): 3
Fold change > 1 implies probes are UP regulated in APP FAT samples.
^ Top Hit Gene
Probe P«Valuβ Q«Val«« Change Top BLAST Annot Accn. Symbol Gene Desc
Cfa.19142.1.S PREDICTED. Equjs caballus XM 0015 1 s at 8.81E-02 J OOE ( OO 4 septm 7 (SEPT7); mRNA 00153 T^Seg similar to Alρha-2- macroglobulln precursor alpha-2-
Cfe.6037.1.S1 (Aipha-2-M) (IOC477699); XM 5346 macroαlob it 9.81E-02 i.OOE+00 0.59 mRNA uliπ similar to Alpha-2- mac/oglobulin precursor alpha-2-
Cfet.6037.1.S1 (Alpha-2-M} (LOC477699); XM 5348 macroQlob s at S.06E-O2 l.OOE+00 0.54 m«NA 93 A2M ulin abhvdroia
PREDICTED: Cams familiaπs δimiiar to alpfia.'aeu hydrolase se domain
Cfa.43β.3.S1 fold ptOrteln; transcript vβrtβπt XM 5361 containing a at 4.36E-02 i.OOE+00 0.64 2 (LOC479037); WRNA 88 ABHD2 2 abhydroia
PREDICTED: Cams famlliaris s similar to alpha/taste hydrolase e domain
CfaAffx.16000. fold ptxΛeirv; transcript variant XM 8446 containing
[ 8] at S.79E-O2 t.OOE+00 0.71 3 (LOC479037): mR!*iA ABHD2
PREDICTED. Cams familiaris similar to Abl-interβctor 2 (Abeison tnteractor 2) (Abi-2) (Ab! binding protein 3) (Ab)BPS) (Arg bisxiing ptotein abl.
CfaAf}χ.1989S. l) (ArgSPl) (LOC4554βS); XM 5456 interactor
1.S1 s at 3,S7£-02 i.OOE+00 0 76 mRNA 06 ABI2 2 anKvnn repeat anc
BT8
PREDICTED: Cams famlliaris (POZ) similar to ankyrin repeat and do 8T8 (POZ) domain containing main
CfeAffx.7032,1 1 iβofotm 2 (LOC609299): XM 8465 containing
.51 at 1,X6£-02 i.OOE+OO 0 75 mRNA 38 ABTB1 1 acetyl- Coenzyme
Homo sapiens cDNA FU60371 A. complete cds; highly similar to
CfaAfftc.17376. Acetyt-CcA carboxylase 2 (EC carboxyias
1.81 s at 6.34E-O2 t.OOE+00 0.34(6.4.1.2) AK302502
PREDICTED: Carns familiaris simllat- to CvtosoliC acyt coeniryme A thlo«$tar hydrolase {Long chain acyl- CoA tfctoester hydrolase) (CTE- π) (CTE'lte) (Brain acyl-CoA acyl-CoA
CfaAffit,29929, hydrolase) (LOC479S89); XM 5367 thioestera
1.S1 s at 6.27E-02 j ooe*oo IM mRNA 27 ACOT7 se 7
56 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
add, phosphate
PREUJCTtD: Cams familiaris s tase 6; e 6. similar to acid phospha
Cfa.14387.1, A lysophosphatklic XM 5330 lysophosp 1 s at 7.17E-O2 t.OOE+00 0.52 (LOC475322); mRNA 30 ACP6 hatidic acyl-CoA svnth
PREDICTED: Cams familiaris etas
Cfa.11382.1. A similar to R6E 10. Ia XM 5376 β farrtj.lv.
1 s at 2.33E-Oi i.OOE÷OO 0.53 (LOC480SS.); mRNA 73 ACSF2 member 2 acyl-CoA synth
PREDICTED: Cams familiaris etas
Cfa.11382.1. A similar to R661Q. Ia XM 5376 e family 1 at 6.66E-02 5,0OE-OO 0.63 (UXHS0551); mRNA 73 ACSF2 member 2 acyl-CoA
PREDICTED: CΛΠIS familioris svnthetas similar to Long-chain-fβtty-aαd e lona- -CoA ltgas« 5 (Long-chain acyj- ch CoA synthetase 5} (LACS 5); ain
Cfa.18640,1.S ttartscript variant S XM 8596 family
1 s at 4.29E-02 S OOEτ-00 1.33 (LOC477S20); mRNA 27 ACSL5 member 5 acyl-CoA
PREDICTED: Cams familiaris svnthetas similar to Long-chairs-fatty-add e long- -CoA Itgasβ 5 (Long-chain acy* ch S); ain CoA synthetase 5} (LACS
Cfa.17404,1.S transαip* variant 5 XM 8596 family 1 s at 3.27E-O2 S.OOE t OO 1.33 (LOC477820); mRNA 27 ACSL5 member 5
ARP1 actiπ- relatecl protein 1 homoloct
PREDICTED: Csnls famillsris similar to ARPl actin-retateβ c protein 1 homotog B; entractin αaAf&(.4436.1 csntractin tieto (LOCβilδδO); XM 8493 beta
.S1 at 4,61E-02 l.OOE t OO 0.77 mRNA 80 ACTR1B (yeast) amino-
PREDICTED: Cams familiaris similar to amino-termmal terminal
Cfa.17603,1.S enhancer of split isoform a XM 5421 enhancer
UL 9.62E-O2 1.00E*00 0.72 (LOC48S064); mRNA
Hcwo sapiens aryl aryl hydrocarbon receptor; mRNA hvdroc (cONA clone MGC:874G1 arb
Cfa.19737.1.S 1MAGE:3O342S82); complete on 1 at S.S6E-02 i.OOE+00 1.33 CdS SC070080 AHR receptor
57 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
v-akt murine thymoma
PREDICTED: Maoca muiatta v vir akt murine thymoma viral al
Cfa.6363.1.A1 oncogene homolog 3 (AKT3); XM 0011 oncogene s at 6,3Sε-O2 i.OOE+00 0.75 mRNA 04624 AKT3 homoloq 3 v-aKt murine . thymoma viral oncogene homolog 3
PREOICTEO: Can* familiaris (prot protein kinase B gamma-iike ein
Cfa.4557.1.S1 protein; transcript variant J XM 5474 kinase S, at 7,9Sε-03 i.OOE+00 0.76 (AKT3); mRNA 96 AKT3 oamma) v-akt murine thymoma viral oncogene homolog 3
PREDICTED: CRΠIS familioris (protein protein kinase S §amma-lιke
CfeAffx.24220. protein; transcript vaiant 3 XM 8581 kinase B,
1.S1 at 1.43E-O2 i.OOE+00 0.66 (AKT3); mR^A 62 AKT3 gamma) alkaline phosphate s
PREDICTED: Cams familiaris e,
CfeAffx.22670. alkaline phosphatase (AlP); XM 5353 liver/bone/
1.S1 s at 4.57E-O3 LOOE+00 0.73 mRNA 74 ALPL kidney amidohydr olase do
PREDICTED: Can* familiaris main
CfaAffx, 10568, similar to T12A2.1 XM 5326 AMDHD containing
1.31 s at 8.45E-02 1.00E*00 0,75 (LOC47S432); mRNA 56 1 1 repeat anc
KHL
PREDICTED: Canls familiaris do Similar to MASK-4E-BP3 main
Cfe.1458S.1,S protein; transcript variant 1 XM 5352 ANKHD containing, 1 at 6,215-02 i.ooε+oo 0.74 (UXδi2748); mRNA 10 1 1 ankyrin repeat anc
KH
PREDICTED: Cams familiaris do similar to MASK-4E-BP3 main
CfaAfix.9676.1 proton; trβnscript variant 1 XM 5352 containing
,,S.1...s...at 3.61E-O2 5,00E-OO 0.67 (1006527^8J; mRNA 10 1
PREDICTED: Squus caballus snkyπn repeat dcmain 26; ankyrin
Cfa.1079.1.S1 transcript vsrisnt 1 XM 0014 ANKRD repeat at 4.84E-O2 i.OOE+00 1.66 (ANKRD26); mRNA 95349 26 domain 26
58 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000060_0001
59 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
PREDICTED: Cams familiaris repeat anc similar to ankynn repeat end SOCS box SOCS box-containing protein Z
CfaAHx.26949. (predicted); transcript variant XM 5479 containing
1.81 at 7,3Sε-O2 i.OOE+00 0.55 1 (LOC490836); mRNA 58 ASB2 2
ATPase. aminopho sphoiipid
PREDICTED: Csnls famillsris traπsporte similar to ATPase; r (APLT). aminophospfioSipscS transporter cl (APLT); ctess I; type SA; ass I,
Cfa.10230.1. A member l; transcript variant 2 XM 8534 type 8A. 1 at 7.69E-O2 1.00E*00 OS (LOC607976); mRNA 76 ATP8A1 member 1
PREDICTED: Cams familiaris similar to Serine/tbreonine- protβin kinase 12 (Aurora- and tpil-like rmdoody -associated prøteln 1) (AIM-I) (Aurora/IPLl -related kinase 2) (Aurora-related Kinase 2) (STK'
Cfa.16355,1.S 1) (Auro^a-B); traπscnpt XM 8549 aurora 1 s at 9.25E-02 5 OOE-t-QO 0.74 variant 4 (LOC479492); mftNA 91 AURKB kinase B
PREDICTED; Cams famϋlarls similar to βeta-l;4- UDP- gslactosyltransf^ase 5 (Seta- Gal:betaGi l;4-Ga:Tase 5) (Beta4Gal-TS) cNAc beta (S-K33I-T5) (UDP- galactos«:beta-N- 1.4- acetylg!ucos«min« beta-X;^ αalactosylt galactossttransferase S) (UOP- ransferase Gal'.beta-αcNAc bet3-S;4- gsUsctosyltransfβfase 5) (Beta-
CfaAfftc.17802. l;4-GafF ll)... (LOC4C5920); XM 5430 B4GALT polvpeptid
1.S1 at 9.59E-C2 l.OOE+00 1.3 mRNA 44 e 5
BMP and activin
PREDICTED: Cam* familiaris similar to BMP and arthrin membran membrane-bound inhibitor e-bouπd homolog precursor (Putative inhibitor transmembrane protefn Nt>tA) ho (Noivmetastatic gene A moloα
CfaAffx.6868.1 protein); transcript s'aoant 1 XM 5442 (Xenopus
,S1 at 5.74E-02 i.OOE-i-00 0.73 (LOC4S70S1); mRNA 09 BAMBi laevis)
HLA-B associate
PREDICTED: Cϋnls familiaris d. similar to HLA-S associated
CfaAfix.1768.1 transcript 2; transcript variant XM 8443 transcript
.S1 s at S.S3E-O2 i.OOE+00 1.46J2 (LOC481713); mRNA 11 BAT2 2
B-cell
Cfe.110.1,S1 Catiis lupus familiaris bd-2 CLL/lvmph S at 3.91E-02 i.OOE+00 0.6SJmRNA for Sei-2; partial eds AB116145 BCL2 oma 2
60 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000062_0001
Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000063_0001
62 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
CDC42 effector protein (Rho
PREDICTED: Can's familiaris
Cfa.11357.1. S similar tv> CdcAZ effector XM 5329 COC42E GTPase
1 at 6.86E-02 1 00E-! 00 0.72 rotein 3 LOC47572S); mRNA 35 P3 binding) 3
Figure imgf000064_0001
63 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000065_0001
64 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
prostate. transmem brane
Sus scfofs mRNA;
Cfa.12544.1.A donp-OVRM10164F12; CR9563 androgen 1 at S.74E-02 S 006-rOO 1.6 expressed in wary AK236216 67.2 induced 1
PREDICTED: Cams famlliarts c similar to CG4774-PA; toarorm ardioiipin
CfaAfix.9880.1 A; transcript variant 2 XM 8448 synthase
•S1 at 6.72E-Oi l.OOE÷OO 0.S8 (IOC6O753O); mRNA 22 CRLS1 1
1WtBO(CTBt/ ."Cai HtVJOTWBnS" slrnllβir to cystattn 9-like
CfaAfJx.7365.1 precursor (I.OC485559); XM 5426 cvstatin 9- .S1 at 6,3Sε-02 S.OOEi-00 0.45 mRNA 77 CST9L like cvstathion ase
(cvstathio
PREDICTED: Cams famlliatis nine
CfaAffr.31268. similar to cyststfitonase XM 5371 qamma-
LSI s at 8.98E-02 i.OOE+OO OJqtsofβrm 1 {LOC4Wθ91); mR)« 15 CTH lyase) cvtochro
Canis fsmilterts cytochrome P- m
Cfa.3883.1.S1 450 UB (MSOUB) mRNA; CYPI1B1 at 4,stε-02 5.00E+00 0.65 complete cds M92447 2B11
PREDICTED: Csnls femillarts diacylQivc similar to newai stem cell- dβrtved dendrite regulatof ; erol αa.2772.2.S1 ttartscript variant 1 XM 5368 lipase, s at 8.13E-O2 S OOE i OO !.?? (LOC1797S6); mRNA 85 DAGLB beta
PREDICTED: Cams familiaris diacyifllyc similar to netiral stem cefl- derived dendrite reguiβtoc; erol
Cfa.2772.1.A1 transαSpt variant 2 XM 8562 lipase, at 5.13E-O2 1.00E*00 1.63 (LOC4797S6); mRNA 53 DAGLB beta dihvdrodio
L
Caπls lupus famiHβrls CAN2DO dehvdi-Qpe
Cfa.3648.LS1 mftNA for dlmeric dfhydrcdloi nase s at 2.11E-O2 l.OOE+OO O.S dehydrogenase; complete cds AB021930 DHDH (dimeric) ic
PREDICTED: Cam* familiaris er 1
Cfa.4679.1.A1 similar to dicerl; transcript XM 8634 ribonuclea s at 6.30E-O2 t.OOE+00 1.41 vaiiaiΛ 4 (LOC460426); mRNA DICER1 se type Hi
PREDICTED: Cams familiaris dermataπ similar to squamous cirfi sulf carclnomβ antigen recognized ate
CfeAfix.842.1. by T cells 2 (LOC483944); XM 5410 epimerase-
SI at S,04£-02 5.00E+00 1.45 mRNA 64 DSEL like
PREDICTED: Cams familiaris similar to Duel specificity dual protein phosphatase 18 (Low specificity molecular weight dual
CfeAffx.395.1. specificity phosphatase- 20} XM 5434 phosphate S1 at 1.6iε-C2 t.ooε+oo 0.77 (LOC486357); mRNA 83 DUSP18 se 18
65 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000067_0001
66 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000068_0001
67 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
fructose-
PREDICTED: Csnls familiaris similar to fructose- 1; 6-
CfaAffx.2650,1 bisphosphatase 1; transcript XM 5335 bisphosph
.S1 s at 7.59E-02 j ooe coo 0.74Jvartant 1 (LOC476299); mftNA 03 FBP1 atase 1 fructose-
PREDICTED: Cams familiaris similar to fructose- 1:6- Ub
Cfa.17541.1. S bisphosphetes* i; transcript XM 8507 bisphosph 1 s at 5.65E-02 5,00E-OO 0.73 variant Λ (IOC<»76299>: mRNA 54 FBPI atase 1
PREDICTED: Pan troglodytes f
Cfa.663.1.A1 box only protein 32; transcript XM 0011 F-box at a,82ε-02 i.OOE+00 O.δsjvanant 1 (FSXO32); mRNA 49252 FBXO32 protein 32
PREDICTED: Cam* familiaris similar to P-box only protein
Cfe.12623.1 A 32 isoform 1; transσipt variant XM 8566 F-box 1 at 6.00£-O3 i.ooε+oo 0.66 3 (LOC47S091); mRNA 32 FBXO32 protein 32
PREDICTED: Canis familiaris similar to F-box only protein
CfaAfftc.2404.1 32 isoform 1; transcript variant XM 8566 F-box
-S1 at 1.77E-02 i.OOE+00 0.7 4 (LOC475091): ittRNA 59 FBXO32 protein 32
PREDICTED: Cams familiaris similar to f-box only protein
CfaAfftc.2404.1 32 isoform I; transcript variant XM 8566 F-box
,S1 s at 2.13E-C-T i.OOE+00 0.6S S (LOC47S091): mRNA 87 FBXO32 protein 32 r(NCdwTEUTraTTwOy>U-[yre» similar to F-box protein 44;
Cfa.2Q844.1.S trsnsσipt variant 9 XM 5143 F-box 1 at 5.2OE-O2 5 DOE ( 00 0.73 (LOC457952), mRNA FBXO44 protein 44
PREDICTED: CΛΠIS familiaris similar to Fibroblast grovrth fibroblast
CfaAffx.25843. factor-18 precursor {FGM8) XM 8493 growth
1.S1 at S.34E-O2 i.OOE+00 0.7 UFGFS) (LQC6US41): mRNA 32 FGF18 factor 18
PREDICTED: Cams familiaris similar to FKSOβ-binding protein 5 (P«ptWyl-pfo!y) αs- trans Isorxerase) (PPIase) (Rot9W3Sβ) (51 kDs FK506- btπding protein) {FK8P-S1 ) (54 kDa progesterone recβptof- associated immunophftn) FK506 (FKB?S4) (P54) (FFl artigen)
CfaAffx.2909.1 (HSPθO-bmdifig Immunophllin) XM 5388 bindino
.S1 at S.22E-O2 i.OOE+00 0.36 { ... (LOC<)Si759); mRNA FKBP5 protein 5
PREDICTED: Canis familians similar to FK50δ-bind<nς proton S (Pepttdyi'piOlyl os- trans tocmarase) (PPlase) (Rotamase) (SX kDa FK50&- binding protein) (FK8P-51) (54 kDa progesterone receptor- associated immunophliln) FKS06 (FKSPS4) (P£W> (FI=I antigen)
Cfa.12375,1.A (HSP90-bindιr>g immunophilin) XM 5388 1 at S.99E-02 5 DOE ( 00 0.38 ( . (LOC4817S9); mRNA 80 FKBP5 protein 5 fibronectin type 111
PREDICTED: Cams familiaris do similar to fibronectSn type Hi main
CfaAfJx.8655.1 domain containing 4 XM 5401 containing
,S1 at 1.40E-02 s.ooε-coo 0.45 (UX4S30H); mRNA 29 FNDC4 4
68 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
PREDICTED: Cams familiβrts simiiar to Forkhead box protein
CfaAfJx.24709, KJ (Myocyte nuctear factor) XM 5470 forkhead
LSI at 2.19E-02 ..0OErOO 0.76 (MNF) (LO048988S); mRNA 03 FOXK1 box K1
Cfa.19616,1.S Homo sapiens forkhead box NM 0020 forkhead 1 at 5.75E-O2 1.0OE-OO 0.72JO1 (POXOl); mRNA 15 FOX01 box 01
FERM
PREDICTED: Cams familiarls do similar to FERM domain main
Cfe-Affx.8025,1 containing 4A (10C607414); XM 8440 FRMP4 containing
,S1 s at 6.29Ir-O? 3.00E-*00 0.76 mRNA 66 A 4A qlucose-6- phosphata
Canis famlliβris glucose-*-
Cfa.204.1.S1 phosphatase mRNA; complete catalytic s at 7.96E-O2 1.00E*00 0.58 cds U91844 G6PC subunjt
PREDICTED: Canls famϋlarls GABA(A) simitar to gsrrwns-arrnnobutyrie receptor- acid (GASA(A)) receptor- associated prσteiπ-iike 1; associate
Cfa.101S0.LA transcript variant 1 XM 8480 GABAR d protein 1 at S.99E-02 i.OOE-i-00 0.75 (LOC6.29.9); mRNA 51 APL 1 like 1
UPP-N- acetyl- alpha-D- galactosa minβ.'polv peptide N-
PREDICTED: Canis familisns acetylαala simiiar to UDP-N-acetyl-alpba' ctos OgΛlactosΛminβ.polypβptidβ N aminyl
CfaAffit,9797,1 scetylςalartosari^ny^ansferss XM 5342 GALNTt transferas
■S1 s at s.9iε-oz 1.00E*00 O.S^e-llXε 2 (LOC477056); mRNA 52 e-ltke 2
Figure imgf000070_0001
69 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Hcmio sapiens guanylste oυanylate cyctes* 1; soiuoie; beta 3; cyclas mRNA (cONA clone e 1 ,
Cfa.253.1,S1 MGC.5i0i2 IMAGE:526<ti60); GUCY1 soluble, at 4.75E-O2 t.ooε+oo 1.39 complete ctfs BC047620 B3 beta 3
2-
PREDICTED: Canls familtarls simitar to 2-hydroκyphytenoyi- hvdroxyac
Cfa.3045.1.A1 CoA Ivase (2-HPCL) XM S342 Vi-CoA s at 7,265-02 S.OOEi-00 0.67 (UX477060); mRNA 56 HACL 1 tøasej.
PREDICTED: Cams familiaris simitar to HMG-box HMG-box transcription factor 1;
CfaAffx.6848,1 tπmscnprt variant 8 XM 8526 transctipti
.S1 at 5.12E-O2 S 006-rOO '6 (LOC475886); ir>RNA 49 HBP1 on factor 1 hypoxia inducible
PREDICTED: Csnls femillarfs f simitar to hypoxι«-ιndudbfβ actor 3,
CfaAffr.7431.1 factor-3 aipna lsoform a XM 5336 alpha
.81 at S,23£-O3 5.00Ei-OO 0.4 (UX476429), mRNA 36 HIF3A subunit hypoxia inducible
PREDICTED: Cams familiaris sirnllβir to hypoxlΛ-lnducibie factor 3.
CfeAffec.7434.1 factor-3 alpha lsoform a XM 5336 aloha
.51 at 2.0iε-02 i.OOE+00 0 74 (LOC476429); mRWA 36 H1F3A subunit hypoxia inducible
PREDICTED: Cams fβmillarts f similar to hvpoxi3-irκjυcιble actor 3.
CfaAffx.7437,1 factor-3 aiphβ rsofonn a XM 5336 alpha
.51 S at 2.73E-O2 i.OOE+00 0.49 (LOC476429); mRNA 36 HIF3A subunit high
Catύs familWrls crossbreed B mobility
Cfa.4558.1,S1 high mobility group HMGAlA group AT- s at M3£-O2 l.OOE+00 0.64 mRNA; complete cds AY366391 HMGA1 hook 1 heteroαen eous nuclear
PREDICTED: Cams familiaπs simiiar to heterogeneous ribonucleo
CfaAfix.10319, nucteai ribonudeopratein L- XM 5329 protein L-
LSI s 5.5SE-O2 s.ooe-!-oo 1.36 like (LOC475729); mRNA 38 HNRPLL I ike
PREDICTED: Csnls famillarls ho similar to Hook homolog 2 (tv moloα 2
Cfa.βO17.1.A1 hook2} (hHK2) (LOC484928): XM 5420 (Drosophil at 9.93E-02 5 ODE -i-OO 1.46 mRNA 44 HOOK2 a)
PREDICTED: Cams famlliaris
Cfa.17416,1.S similar to hιppoc3lcirι-lik.e i XM 8471 hippocalci 1 s at 6.90E-O2 1.00E*00 0.63 (LOC6097S7); mRNA 24 HPCAL 1 n-jike 1
PREDICTED: Cams fsmiliatis hvdroxypr similar to IS- ostaglandi hydroxvpmstaglaixlin U dehydrogenase fNAO-t-] [PGOH) (Pfostaglanciin dehydroqe
CfaAfix.12647. dehydrogenase 1) XM 5431 nasβ 15-
1.51 at 3JSε-02 i.OOE+00 0 7 (LOC486073), mRNA 99 HPGD (NAD)
70 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
hegsiji
PREDICTED. Cams famHlaris (transme similar to Serine protease hepsin crransmetnbfane mbrane
CfaAfftc.11565. protease; serine 3) XM 5416 protease,
1.S1 s at 9.11 £-02 i.ooε+oo 0.74 (LOC484Sa3); mRNA 97 HPN serine 1 ) v-Ha-ras
Harvey rat sarcoma viral
Cfa.3598.1,S1 Cams familiaπs ras p21 (H-ras) oncogene s at 4.58E-O2 l.OOE+00 0.?7|mRNA; partial cds U62092 HRAS homoloo. hydroxy- delta-5- steroid clehvdroqe beta- and steroid
Cartis farrtilβris >beta- delta-
Cfa.13172,1.S hydroxysteixΛI rieiiydiogenase isomerase
1 at 4.81E-02 S OOEτ-00 0.66fmRNA; complete cds AY739720 HSD3S1 1
HIV-1 Tat
PRFOICTFD: Cams fsmiliaris int siwiiβr to HlV-I Tat interactive eractive
CfaAfrx.15407. protein 2; 3OkOa XM 5340 protein 2,
1.31 at 7.SiE-Oi l.OOE+00 1.5« (LOC476886); mRf-JA 88 3OkDa
HIV-1 Tat
PREDICTED: Carns familiarls int similar to HIV-1 Tst interactive eractive
CfeAffx, 15407. protein 2; 3OkOa XM 5340 HTATIP protein 2,
1.81 s at S.9SE-O2 l.OOE+00 1.44 (LOC476S86); mRNA 88 30KDa
PREDICTED: Cams familiaris hvdroxytry similar to 5-hydroxytιypt.atnirte ptamine IE receptor (5-NT-1E) (Serotonin receptor IE) (5- (serotonin
CfaAffx.5506,1 HTXi) (S31) (U3C461907); XM 5390 ) receptor
.S1 at 3.2SE-O3 5 0OE ( 00 1.32 mRNA 28 HTR 1 E 1E hydrogen
PREDICTED: Cams familiaris hypottieticai protein volte?
Cfa.βO77.1.S1 LOC608547; transcript variant XM 8565 pated at 4.41E-02 l.OOE+00 0.6S 3 (LOC60SS^7}; mRNA 80 HVCN1 channel 1 hydrogen
PREDICTCD: Cams familiarls volt hypothetjcai protein age-
CfaAfftc.13473. LOC606547; transcript variant XM 8565 1.31 s at 7.75E-02 1.00E*00 0.71: 3 (LOC608S47); mRNA 80 HVCN 1 channel 1 hvdroxypy
PREDICTED: CRΠIS familioris similar to hydroxypyruvate isomerase
CfaAffx.8742,1 isotnefBse homclog XM 5396 homoloo
■S1 s at 7.S2E-O2 l.OOE+00 0.63 (LOC482531), mRNA 48 HYI (E. com Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
islet cell
PREDICTED: Csnls fiamillarls similar to islet cell autosntigen autoantiqe
CfaAffx.4263,1 1 isoform 1; transcript variant XM 8566 QJL
.S1 s at 1.36E-02 j ooe coo 1.41! 6 (LOC475242); mRNA 89 ICA1 69kDa
PREDICTED: Csnls famillarfs int similar to IrsberferorWnducecl erferon-
Cfa.16440.1.S 35 kDa protein (If=P ZS) XM 5480 induced
UL 9.85E-02 i ooe coo 1.58 (LOC4θ0954); mRNA ZZ IFI35 protein 35
PREDICTED: Cams familiaris int similar to Interferon-lnduced erferon-
Cfa.18820.1.S 35 kDa protein {ϊfψ 3S) XM 5480 induced 1 at s.aiε-02 l.OOE+00 .38 (LOC490954), mRNA 77 IFI35 protein 35 interferon-
PREDICTED: Cams familiaπs related simiiar to interferon-retetec! developmental regulator 1; deveiopm
CfaAffx.5908.1 transcript variant I XM 5395 ental
.S1 at 7.92E-02 5,00E-OO 0.52 (100182*08); mRNA 25 IFRD1 regulator 1
INO80
PREDICTED: Cams familiaπs
CfaAfrx,2Q601. similar to CG7S32-PA XM 5456 complex
9.46E-02 1 0OE ( 00 1.34 (LOC4SS489); mRNA IS INO80D subunit D
PREDICTED: Canls (axillaris similar to lnsuiin receptor
CfaAffx.27879. precursor (IR) (CD220 XM 5421 insulin
1.S1 s at 3.S1E-O2 l.OOE^OO 0.74 antigen) (LOC484990); mRNA 08 INSR receptor iQ fTrøtif containino
PREDICTED: Cams familiaris GTP similar to Ras GTPase- ase
Cfa.15284.1. A sc«vatin§-l!ke protein IQCSAPt XM 5361 activating 1 s at 9.31E-02 ..00E-OO 0.75 (pJ95) (LOCt79060); mRNA 99 IQGAP1 protein 1
IQ motif containing
PREDICTED: Canis familiaris GTP similar to Ras GTPase- ase
CfaAHx.19884. activatiπg-tiks protein IQGAPl XM 5361 activating
1.S1 s at δ.47£-O2 j.ooε+oo 072 (pl95) (LCX479O50); mWiA 99 JQGAPI protein 1 immunore
PREDICTCD: Cams familiaris sponsiv similar to IMMUNE- e 1
CfaAfftt,8S31,1 RESPONSIVE PROTEIN 1 XM 5426 homolog
,S1 at 7.53E-02 1.00E*00 lJ7 {LOC485<*%); mRNA 15 IRG1 (mouse) inteqrin,
PREDICTED: Cams familiaris alpha 2 similar to Irstsgnn alpha-2 (CD49B. precursor (Piatetet membrane alph; glycoptoteln Ia) (GPIa) subunit of (Coiiβgen receptor) (VLA-2
CfaAffx.26187. 3lprw chain) (COtSb) XM 5463 VLA-2
1.S1 at 5.19E-Oi l.OOE÷OO 0.73 (LOC489208); mRNA 26 ITGA2 receptor) rt^sTTrsTetTimsrTa similar to iπtegnn; alpha D
CfaAfix.22104. piwursor (LOC607096); XM 8436 inteorin. 1.S1 at t.ΗE-02 l.OOE+00 0.69 mRNA 83 ITGAD alpha D
72 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000074_0001
73 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000075_0001
74 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000076_0001
75 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000077_0001
76 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
similar to
L-lactate dehvdroqe chain
PREDICTED: Cams familiars (LDH-B) similar to l-lacwte (LDH dehydrogenase 8 diain (LDN- h B) (LOH neart subunit) (LDH- eart
CfaAffr.1319.1 H); transcript vβrsnt 1 XM 5334 LOC476 subun.itl
■S1 s at 4.SSE-Qi i.OOE÷OO 0.71: (IOC4?6_U); mRNA 18 213 (LDH-W hypothetic
PREDICTID: Canis familiaris al
CfaAflx.β020.1 hypotheticai LOC476444 XM 5336 LOC476 LOC4764
-S1 at 2.43£-O2 t.ooε+oo 0.75 (LOC476444); mRWA 50 444 44
similar to
CDK2
(cydin-
PREDICTED: Cams fβmlliaris dependenl similar to COKZ (cycl-n- kinas dep«rtdent kinase 2)- e 2h
Oa.10960.2.A associβted protein l XM 5346 LOC477 associate
1 a at s.ssε-02 i.OOE+00 37 (LOC477452); mRNA 50 452 d protein 1
PREDICTED: Cams familiaris
CfaAfix.14325, similar to F09812.3 XM 5346 LOC477 similar to LSI at 1.32E-O2 S OOE i OO 0.6S (LOC-177^93); mRNA 91 493 F09B12.3 similar to ϊt chimaerin
(NC) (N- chimen'n) (Alpha chimerin)
{A;
PREDICTED: Cams familiaπs chimaerin) similar to N-dnmaerin (NC) (N (RhO- chlmeiin) (Alpha chlmefin) (A- GTFase- chlmaβfiπ) (Rho-<ϊTPase-
CfaAffx.20586. activating protein 2), transcπpt XM 8562 LOC478 activatiπα
1.81 s at 9.00E-O2 t.OOE+00 -."SJvanaπt 3 (LOC47880S): mRNA protein 2) hypothetic
PREDICTED'. Cams familiaris SL
CfeAffx.29155. hvpotheticβ) LCC479382 XM 5365 LOC479 LOC4793
LSI s at 3,965-02 i.OOE+00 0.64 (UX479332); mRNA 20 382 82
77 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000079_0001
78 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
similar to reqenerati
20. associate
PREDICTED: Can* familiaris d similar to regeneration muscle
CfeAfix.11212. associated tnusde protease XM 5405 LOC483 protease
1.81 s at S,47£-OZ i.OOE+00 0.42 isoform b (LOC4B5426); mRNA|44 426 isoform b
similar to
Caspase recruitmen t domain protein 8
(Apoptottc protein NDPPD (DACAR)
(CARD- inhibitor of NF- kappaS activating liαand) (CARDIN
PREDICTED: Cams familiars ALI similar to Caspase recruitment (Tumor-uι> domain protein 8 (Apoptotic proton MOPPl) (DACAR) repulated (CARDHnhlbitor of NF-kappaB CARD- activating tigand) (CARDINAL) coπtainino (Tumor-up-regulatβd CARD- antagonist containing βmagonfst of
CfaAfix.6973.1 CASW) (TUCAN) XM 5415 LOC484 of CASPΘ)
.81 s at 3.S9E-02 5.00Ei-OO 1.54 (L0C484411); mRNA 26 411 (TUCAN) similar to cytochrom e P450, family 2.
PREDICTED: Cams familiaris subfamily simifar to cytochrome MSO; family 2; subfamily S;
CfaAfix,8S07,1 polypeptide I (L0C484491); XM 5416 LOC484 polvpepticl
81 a* 3.52E-O2 1.00E*00 0.75 mRt^A MJ, si
PREOICTEO: Can* familiaris milar to
Cfa.20718.1.S similar to Protein KΪAA1434 XM 5429 LOC485 Protein
1 s at 7.10E-02 i.OOE+00 0.6S (LOC485778); mRNA 01 778 KIAA1434 similar to
CXYorfi-
PREDICTED: Csnls famtilaήs
CfaAffx.24113. similar to CXYorfi-related XM 5438 LOC486 reiated
1.S1 s at 2,2aε-02 i.OOE+00 071; protetπ (LOC4S6746); mRNA 73 746 protein
79 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000081_0001
SO Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000082_0001
Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000083_0001
S2 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
similar to
Cytochro me F45Q 27, mitochond rial precursor
(Cytochro me P- 450C27/2 5) (Sterol
2& hvdroxyias e) (Sterol
27; hvdroxylas el
(VHamin DO) 25- hvdroxylas e) (5-beta-
PREDICTED: Cams familiaris cholestaπ similar to Cytocfcrome P450 e-3- 27; mitochondrial precursor alpha.7- (Cytochrome P-450C27/.5) (Sterol 26- hydroxylase) (Sterol alpha,12- 27-hydroxylase) (Vtemln D(3) alpha-triol 2S-bydroxylase} (S-*et»- cho)βstane-3-alpria;?-alpha; H- 27;
CfeAffx.22992. alpta-trtol 27-hydroxylase) XM 8480 LOC610 hvdroxyias
1.S1 at 4.D5E-O2 L0OE+O0 0.64 (LCK6104S9); mRWA 01 489 e) similar to Cvtochro me c oxidase polvpeptid
PREDICTED: Cams fβmillarts e Va. similar to Cytocttrtwe c oxidase polypeptide Va; mitochond
CfeAffx, 13327. mitochondrial piecυrsor XM 8488 LOC610 rial
1.81 s at S,9Sε-O2 i.OOE+00 0.69 (LOC610768); mRNA 59 768 precursor si
PREDICTED: Cams famlliaris milar to
CfaAffx,S042,1 similar to CG9166-PA XM 8487 LOC611 CG9166-
81 s at 7.52E-O3 1.00E*00 0.68 {LOC611116); mRNA 57 1 ' PA si
PREDICTED: Cams familiaris milar to
CfaAffx.31158, similar to CGU 125-PA XM 8487 LOC611 CG11125- 1.S1 at 1.33E-O3 S 006-rOO 1S (LOC611150); mRNA 94 150 PA similar to Hypothetic
PREDICTED: Cams famlliaris UPF0195 similar to Hypcttefecal
Cfa.14385.1.S UPfOlSS protein CGi-IiS XM 8489 LOC611 protein 1 s at S.07E-O2 t.OOE+00 0.67 (LOC6U30.); mRNA 51 301 CGI- 128
S3 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
similar to
Hypothetic al
PREDICTED: Canis familians UPF0195 similar to Hypothetical
Cfa.14385.2.S LJPF0195 protein CGI-128 XM 8489 LOC611 protein 1 s at 4.38E-02 S 006-rOO '4 (LOC655301); mRNA 51 301 CGI-128 similar to
Hypothetic
Si.
PREDICTED: Cams famlliaris UPF019S similar to Hypoth«tjcal
CfaAfftc.31224. UPfOlSS protein CGi-IiS XM 8489 LOC611 protein
1.81 s at 3.39E-O2 l.OOE+00 0.6S (LOC6U30.); mRNA 51 301 CGI-128 similar to
Hypothetic
PREDICTED: Canis femϋlarfs M. UPF0195 simitar to Hypottietttal
Cfa.1438S.2.S UPF0195 protein CGM28 XM 8489 LOC611 protein 1 x at 1,13£-O2 5.00Ei-OO 0.65 (IΛC6..301), mRNA 51 301 CGI-128 similar to oyary-
PREDICTED: Cams familiaris similar to ovary-soecific MO8- spβcific
OaAIfK.15695. like protein (LOC6U494); XM 8491 LOC611 MOB-like
1.S1 at S.13ε-02 i.OOE+00 0 69 mRNA 65 494 protein similar to Interferon-
PREDICTED: Canis familisns
CfaAffr.15732. simitar to Inlerfisron-inetuαbte XM 8492 LOC611 inducible
LSI at 4.04E-02 1.00E^OO 0.59 proton (LOC611S37); rnRNA 17 537 protein similar to
60S
PREDICTED' C«nιs f»mi|ι»rιs riboso similar to 60S iibosomsl mal
CfeAffx.2570P. protein L26-!tke 1 XM 8492 LOC611 protein
1.S1 s at 672ΪJ-04 l.Oϋt+00 0.6V (LQCδUSVϋ); mRNA 54 570 L26-like 1 similar to 60S
PREDICTED: Canis fartiiliaris riboso similar to 60S nboscmai mal
Cla.4706.1,A1 prøtein U6-like 1 XM 8492 LOC611 protein at 8.56E-02 i.OOE+00 0.77 (LOC6U570); mRNA 54 570 L26-like 1 hypothetic
PREDICTED: Cams familiaris hypothetjcai protein al protein
CfaAfftt, 10678, U3C611604 (.OC511604); XM 8492 LOC611 LOC6116 l&LJL 2.67E-O2 1.00E*00 0.76 mRHiA similar to
PREDICTED: Carns familiaris
CfaAHx.12328. similar to atonal homolog S XM 8497 LOC612 atonal
1.81 at 7.1SE-02 i.OOE+00 0.72 (LOC6U024); mRNA 51 024 homoloo 8
U Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000086_0001
S5 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000087_0001
86 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
PREDICTED: Cans familiarls similar to Melanoma- associated antigen D2 (MAG6- D2 antigen) (MAGE-D) (Breast cancer associated gene 1 protein) (BCG-i) (1186) (Hepatocellular carcinoma associated protein X3.-1); melanoma
Cfa.3975.2.A1 transcript variant U XM 8597 MAGED antigen at 6.28E-O2 l.OOE+00 .34 (IOC480934); mRNA 82 family D, 2
PREDICTED: Cams familiaris similar to Melanoma- ssscdated antigen 02 (MAGE- 02 antigen) (MAGE-D) (Breast cancer associated gene 1 protein) (BCG-I) (1186) (Hepatocellular carcinoma associated protein JCl-I); melanoma
Oa.2153β,1.S transcript variant 11 XM 8597 MAGED antigen
1 at 3.42E-02 ..0OErOO .33 (LOO480934); mRNA 82 family D. 2 microtubul
PREDICTED: Pan troglodytes associate
Cfa.2709,1,A1 microtubule-associated protem XM 5177 d protein
6.75E-02 5 OOe-fQO 1.7S IS (MAP18): mRNA is MAPI B IB
PREDICTCD: Cams familiarls sirnilar to C-jurs-amino-terminal kinase interacting protein I mitoαen- (JNK-interactirsg protein i) (JIP activated 1) (JNK MAP kinase scaffold protein protein I) <Istet-braln-J) (58-1! (Mitogeπ-actJvatec- protein kinase 8 αaAfix.14768. kinase S-irsteracting protøn 1) XM 5407 MAPK8I interacting
1.S1 at 5.60E-02 i.OOErOO 72 (LOC4S3640); mRNA 60 P1 protein 1 micfotubυl
S: associate
PREDICTCD: Cams familiarls d protein, similar to microtubule* associated protein; RP/EB RP/EB
Cfa.10212.1,A family; n»enibe>* 3; transcript XM 8547 MAPRE family, 1 at 3.176-C2 J.OOE+00 0.7 variant 3 (IOCA7S694); mRNA 88 3 member 3
PREDICTED: Cam* familiarls similar to Microtubule- microtubul ssscciated protein tau (Netitofibiillaiy t«ιt\gie μtotein) (Paired helical filament-tau) associate
CfaAffx.21136. (PHf-tou); transcriot variant 3 XM 8552 d protein
1.81 s at 9.18E-02 J 0OE ( 00 0.67 (LOC480488), mRNA MAPT tau minichrom osome mainteπan
PR601CTED: Cams familiaris ce sirnllβir to minictwmσsome maintenarsce protein 8 isoform complex
Cfa.10118.1.A 1; trarsscπpt vansnt I XM 5343 componen
1 at 9,3iE-02 5.006*00 0.73 (UX477J63); mRNA 52 MCM8 t 8
Hl Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000089_0001
Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
mitochond rial
PREDICTED: Cams familiaris riboso similar to mitochondrial mal
CfaAfftc.12433. ribosotral protein £36 XM 5352 MRPS3 protein
1.S1 s at 2.76E-O2 t.ooε+oo 0.76 (LOC478035); mRNA 62 6 S36
PREOICTEO: Cams familiaris simitar to Mσesirt (Membrane- organteing extension spfke
CfaAfSx.25424. protein); transcript variant 2 XM 8432
LSI at 7.82E-02 1.00EfOO 1.32 (UX49S924); mRNA 43 MSN moesin
PREDICTED: Caπls familiars simitar to SiβSdase I precursor (Lysosomal sislidasej (N-acetyl alpria-neuraminicSase S) sialidas (Acetylneurawiny* hydrolase) e 1
Cfa.S42.1.A1 (G9 sialSdase) (LOC481717); XM 5388 (lysosoma at 5.64E-02 5,00E-OO 1.36 mRNA 38 NEU1 sialidase)
PREDICTED: Cams familiaris similar to X-(!nk«d neuiOligiii 4; αaAf&(.17532, transcript variβnt l XM 8432 neuroligin LSI s at 2.B7E-O3 l.OOE+00 0.« (IOC6Q7*Q6); mRNA 64 4. X-linked non- metastaiic cells 1. protein
(NM23A)
Cartis lupus famitiaiis nm23-Cl αaAf&(.26479, mftNA for NM23-CI; compifite expressed
LSI x 5.3OE-O2 i.ooe-t oo 1.86 cas AB207044 NME1 in
PREDICTED: Canis familiaris similar to expressed in rtort- metβistatic cells 1; pjoteln (NM23A) (riueieostrfe
Cfa.15094.1.S diphosphate kinase) XM 5339 NME1- 1 a at 2.87E-02 l.OOE^OO 2.2 (LOC476767); mRNA 73 NME2 NME2 nucleolar protein 3
(apoptosis repressor with
PREDICTED: Cam* familiaris
Cfa.16171.1.S similar to nucieolar protein 3 XM 8488 CARD
2.59E-O2 t.OOE+00 1.33 (L0C6U249); mRNA NOL3 domain)
Bos taurus nuclear receptor nuclear binding factor 2; mRNA (cDMA receptor done MGC: 143396
Cfa,11099.1,A tMAGE:81427S9), complete binding 1 at XUZ-02 i.OOE+00 0.72 zόs SC 123769 NRBF2 factor 2 neurotrop hie tyrosine trkC {altemativeJy spiiced}
Cfa.2717.LA1 [human; brain, mRNA; 2225 receptor, a at 3.48E-02 1 006-rOO 0.69 rrt} S76476 NTRK3 type 3
S9 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000091_0001
90 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
pyruvate
PREDICTED: Cams familiars dehydroqe similar to pyruvate πas dehydrogenase kinase; e
CfaAflx.25S4S. isoenzyme 2 (L.OC491Q75); XM 5481 kinase,
1.S1 at 7.97E-02 S 006-rOO 0.7 'S rnRNA 95 PDK2 isozyme 2 fKtuiu I &u; tanis rarvwiaris similar to [Pyruvate dehydrogenase [lipoamideD pyruvate kinase isosyme 4; dβtiydrogβ mitochondrial precursor nas (Pyruvate dehydrogenase e
CfaAfftc.4097.1 kinase isoform 4} XM 5394
,S1 s at 3.06E-O2 l.OOE+00 0.36 (LOC482310); mRNA 27 PDK4 isozyme 4 platelet endothelia
L aααr
PREDICTED: Cam* familiarls eoatio
CfaAffx.25273, similar to MBSFtO protein XM 5475 n receptor
1.31 at 8.10E-02 l.OOE+00 0,75 (LOC49CW03); mRNA 24 PEEAR 1 1 platelet endotheiia aggr
PREDICTCD: Cams familiarls eoatio
CfaAfrx.25273. similar to MEGFlO protein XM 5475 n receptor
1.31 s at 4.68E-02 l.OOE+00 0.73 (LOC4M4O3); mRf-JA 24 PEAR1 1
PREDICTED: Cams familiarls phosphogl similar to 6^-
CfeAffx.23485. phosphoρluconolactonsse XM 8474 uconoiact
1.81 at 6.36E-O2 i.OOE+00 0.76 (LCK610090); mRNA 89 PGLS onase
PREDICTED: Canis farniliaris PHD similar to PHD finger protein
Cfa.14949.1, A IS; tfa)_5cript variant ? XM 8570 finger 1 s at 1.93E-02 i.OOE+00 0.68 αθC48i508); mRNA 72 PHF15 protein 15
PREDICTED: Cams famlliaris similar to Phαsphotγlsse b phosphory kinase alpha regulatory chain; lase liver isofortn (Phosphorylase kinas kinase alpha U suBunft); e,
Cfa.5653.1.A1 transcript variant 1 XM 5379 alpha 2 at 3.0SE-O2 5.00E+00 1.44 (LOC46QS57), mRNA 74 PHKA2 (liver)
PREDICTED: CRΠIS fawillβrβ simllat- to Prtosphorylase b phosphory kinase alpha regulatory chairs; lase liver isoform (Phosphoryiasβ kinase alpha i. susuna); αaAfix.20064. transCTipt vβrtβnt 4 XM 8533
LSI s at 6.65E-O2 l.OOE+00 1.32 (LOC4S0SS7); mRNA 25 PHKA2
Figure imgf000092_0001
phvtanoyl-
PREDICTED: Cams familiarls similar to prtytarmyi-CoA
Cfa.15689.1.A hydroxylase precursor XM 8442 hvdroxylas
LM 6.48E-02 l.OOE+00 0,42 (LOC478001); mRNA PHYH I Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000093_0001
92 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000094_0001
93 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
P.hosphatj
PREDICTED: Csnls famillarls <M s similar to phosphstiβylsertne erine
CfaAffx.10730, synthase 2 (IOC4S3401); XM 5405 synthase 1.S1 at 5.23E-O2 5 OOE-t-QO 0.73 rriRNA 20 PTDSS2 2 prostaqlan din E r
Cante familiars prostaglandin eceptor 4
Cfa.34S2.1.S1 £2 receptor EP4 subtyp* PTGER (subtype s at 5.39E-Oi i.OOE÷OO 1.!MJmRNA; complete cds AF 177934 4 EP4)
Qlutaminvi' tRNA
PREDICTED: Cams familiarw synthase simiiar to glutaminyl-tRNA (giutaminβ' synthase (glutemine-
CfaAffx.6541.1 hydrolysinoj-llke i XM 5322 hvdrolvzin
■S1 s at 4.44E-O2 1.00E*00 0.74 (LOW7SQM); WRNA 50 QRSL1 αV-like 1
RAN
PREDICTED: Cams familiaπs
Cfa.20264.1.S simiiar to RAN binding protein XM 5358 RANBP binding 1 s at 6.60E-02 J 0OE ( 00 0.75 9 (LOC47872S); RiRNA 93 protein 9
Rap guanine
Homo Mpietts Rap yuafiπe nucleotide nucleotide exchange factot exchanαe (GE?) S; mRNA {CDNA Ctone
Cfa.21620.1.S Mt3C:26203 1MAG£:43U<»83); factor
1 at 2.52E-O2 1.00EfOO 1.49 corrsptete c4s BC039203 (GEF) 5
RNA terminal phosphat
PREDICTED: Caπls familiaris e
CfeAffx.4051.1 similar to RNA cyclase XM 5412 cvclase-
.S1 s at S,SS£-02 l.Oϋt+00 0 76 homotog {LOC4S4183}; mRNA 99 RCL1 like 1
PREDICTED: Cams fawiiiafis similar to Retiπol dehydrogenase U (Retinal reductase 1) (RaIRl) (Prostate short-chaSn tJefiydrogenasβ/rβductas* 1) retinol {Aπdrogcn-neguiated short- dehvdroge chain nas 11 dehvdrogenase/redudas« 1) e
Cfa.2Q00β.1.S (YKM core-binding protein XM 8492 (all-traπs/9
1 at 8.2SE-02 S.OOEi-00 .37 HC8P12) (LOC480366); mRNA 61 RDH 11 cis/ 11 -cis) similar to reelin isoforw b;
Cfa.9467.1.A1 transcript variant I XM 5403 at 3.69E-O2 l.OOE+00 1.59 (LOCTS3273); mRNA 92 RELN reelin fϋπgo dϋciu IΠHINH; LUIVM
Cfa.3701,1.S1 DKF2P469I191 (from ctone
7.10E-O2 1.00E*00 0.63 DKr7p469U91) CR926484 REN renin
PREDICTED: Cams familiaris similar to ONA repair protein REV1 REVi (RevHlke terminal homoloα (JeoxycyDdyl transferase) {Alpha integrin birtding protein
Cfe,470.1,A1 SO) (AΪBP80) (LOC48t337); XM 5384 cerevisiae at 1.32E-02 i.OOE+00 0.42 mRNA 58 REV1 )
94 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000096_0001
95 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
SH3-
PREDICTED: Can.s familisns domain
CfaAffx.16684, simiiar to SHJ-dcnaiπ binding XM 5432
1.S1 at 9.17E-02 5 OOE-fQO 0.66 protein 4 (L.OC486172); mRNA 98 SH3BP4 protein 4
SH3- domain
PREDICTED: Cam* familiaris binding similar to SH3 domain-binding protein 5 protein 5 (SH3 domain-binding protein that preferentially (BTK-
CfaAffx,S996,1 associates with EfTK) XM 5427 associate
2.8OE-O2 5 OOE-fQO 1.4 (LOC485657), mRNA ZZ SH3BP5 dj
PREDICTED: Cams fsmiliaris shroom
CfaA*ix.13β80. similar to shroom XM 8449 SHROO family
1.S1 s at 9.34E-03 5,00E-OO 0.72 (LOC-178^38); mRNA 10 M3 member 3
S1D1 transmem
PREDICTED: Canis familiaris similar to S30I transmefTibfaw brane
Cfa.21475.1,S family; menibe." 2 XM 5465 family, 1 at 2.7SE-02 i.OOE+00 0.74 (LOC48939-); mRNA 09 SIDT2 member 2
solute carrier
PREDICTED: CRΠIS fawillβrβ family 12 similar to Soiute carrier family (potassiu 12; member 7 (Etectroneutrβi m/chioride potassfum-chlorids cotransporter 4) (K-Ci transporte
CfaAfix.169Q0. cotransporter 4) (LOC488069); XM 5451 SLC12A rsL
LSI s at 9.11E-03 l.OOE+OO OJ^ mftNA 93 member 7 solute carrier family 16, member 1
(monocar
PREDICTED: Cam* familiaris boxylic similar to Monocarboxyiate tfsnspciter 1 (MCT 1); acid
Cfa.19806.1.S transcript variant 3 XM 8575 SLC16A transporte 1 s at 7,935-02 S.OOEi-00 0.73 (LOC475S56), mRNA 92 LΛ ) solute carrier family 27
PREDICTED: Canis familians (fatty acid simiiar to soiute carrier family 27 (.fatty acκl transporter); transporte
Cfe.16871.LS member 6 (LOC474666); XM 5318 SLC27A
1 at 5.07E-Oi i.OOE÷OO O.W mRNA 94 member 6
96 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
solute carrier family 27
PREDICTED: Cams familiarw (fatty acid simiiar to soiute offh» familv 27 (fatty acKi transporter), traπsporte
CfaAffx.2004.1 member 6 (S.OC474666); XM 5318 SLC27A ∑L
.S1 s at l.UE-02 J OOE-OO 0,<?8 mRNA 94 member 6
solute carrier familv 37
(glycerol- 3 phosphate
PREDICTED: Cams familiarls transport similar to soiυte ea>ner family e
CfaAffx, 16375, 37 member i (LOC487780); XM 5449 SLC37A
1.31 s at 8.39E-03 1.00E*00 0,66 mRNA 05 1 member 1
solute carrier family 3 (activators of dibasic and
PREDICTCD: Cams familiarls neutral similar to soiυte ea>ner family amino 3 {activarors of (tibawc and neυtrai amino sod transport), acid
CfaAffx.23808. nvember 2 Isoforπ a XM 5408 transport),
1.51 at a,/ss;-02 i.oot+oo I 74 (LQC44WΛ0, mRNA 98 SLC3A2 member 2 solute carrier family 7 (cationic
PREDICTED: Cam* familiaris amino similar to Large neutral ammo acid sods transporter small subunit transporte 2 (L-type amino acid transporter 2) (hlAT2}; LXL
CfaAffx.17822. transcript vartant 7 XM 8535 system),
1.S1 at 1.36E-02 J OOE i OO 0.7S (LOC49060S), mRNA 54 SLC7A8 member 8 solute carrier organic anion transporte r familv,
Cams familiaris prostaglandin
Cfa.16330.1.S transporter mRNA; complete SLCO2A member 1 s at 3 80E-O2 t.OOE+OO 0.69 αis AY879310 1 2A1
97 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
SWI/SNF related, matrix associate d. actin dependent
PREDICTED: Cams familiars regulator similar to SWI/SNP-related of. matrix -associated aetin- chromatin, depersdent reguiator of subfa chromatin al iscform a; mily
Cfa.1831.1 Al transcript variant 19 XM 8604 SMARC at 5.58E-02 5,00E-OO 1.37 (LOθW_CM6); mRNA 93 A1 member 1
PREDICTED: Cams familiaos
CfeAffx.21915. similar to SWl-like kinase 2 XM 5465 SNFUK SNF 1 -like 1.S1 at 6,2Sg-02 l.OOE+00 0,69 (LOC4S9410); mRNA 28 kinase 2
PRHDICTED: Cams farniliaris similar to Sterol 0- acystraπsferase 1 (Qiofesteiυl acyitfansferasβ 11 (Acyl sterol Q- coenzyme A:*oJesterol
CfaAffx,2145S. acystransferesa i) (ACAT-I) XM S474 acyltransf
LSI at S.37E-O2 1.00EfOO 0,64 (UX490325); mRNA 45 SOAT1 erase 1
PREDICTED: Cams familiaris slwilar to SON DNA- binding SON DNA αaAfix.14389. protein isoform A; transcr-pt XM 8516 binding
LSI at δ.%E-02 l.OOE+00 ,SS variant 4 (LOC478406): mftNA 35 SON protein
PREDICTED: Cams familiaris similar to SOW DNA-b)ncSlng SON DNA protein isoform A; transcript
CfaAffr, 1703,1 variant 14 (LOC47S406): XM 8520 binding
-S1 x at 9.64E-02 1.00E*00 1,99 mRNA protein sorbin and
SH3 domain
PREDICTED: Cams farniliaris
Cfa.17029.1. S similar to SH3 domain protein XM 5345 SORBS containing 1 at 4.04E-02 5,00E-OO 0.69 4 {IOC4773S3}; wRNA 77 3 3
PREDICTED: Cams familiarls SRY (sex similar to SRY (sex determining regkxi v)-tκ)x S determinin
CfaAHx.18082. soform a; transcript variant 10 XM 8608 q region
1.S1 s at i.oiε-02 t.ooε+oo 0.67 (LOC486635); mRNA 88 SOX5 YVbox 5 secreted
PREDICTED: Cams familiβfis protein, simiiar to SPARC p^ecursof acidic. (Secreted protein aαdic aικt cysteine; rich in cysteine) (Osteonectin) rich (ON) (Basement-membrane
CfaAfftc.27328. protein 40) (BM-O) XM 8498 (osteonect
1.S1 s at i.ooε-02 t.ooε+oo 1.38 (LOC6121S9); mRNA 89 SPARC ifil
98 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
spastic^ paraplegia
3A. (autoso
PREDICTED: Cβnis familiaris me
Cfa.20143.1.S similar to attasbn- transcript XM 5374 L 1 at 9.41E-02 S 006-rOO Invariant 1 (LOC480316); mftNA 40 SPG3A dominant) sparc/oste onectin, cwcv and kazal-like
Homo sapiei\s ciomains sparc/osteβnedsn; cvvev and proteoqlvc k3tal-!lke domains an proteoglycan (testiean) 2
Cfa.4366.1.A1 (SPOOC?); transαipt variant ?; NM 0147 (testican) s at 9.23E-02 5,00E-OO 0.68 roRNA 67 2
Bos tourus sponsin 2; exbacefiuiar maϋix pfoteiti, spondin 2. mRNA (cDNA clone MGC:t380SS extracellul
CfaAffx.25530. tMAGe:S08605?): complete ar matrix
LSI at 2.7SE-03 J 0OE !-00 0.69 cds BC113291 SPON2 protein
ST8 alpha
N-acetyl- neuramini de aloha-
Homo sapiens STB alpha-N- 2J1 scetyt-neuraminkte alpha-2;8-
Cfe.16366.1. A sialyltransfe«s« 4 (ST8SIA4); NM 0056 ST8SIA siatyltransf 1 at S.37E-O2 i.OOE+00 1.47 transcript vailant 1; mRNA 68 erase 4 signal transducer
PREDICTED: Canis farniliaris and similar to Signal transducer activator and activator of transcription 1 oL alpha/beta CTranscription transcript! factor ISGF -3 components
Cfa.20754.1.S p9i/p84); transcript variant 4 XM 8508 on 1 , 1 at 8.30E-02 5 0OE !-00 .33 (LOC4SS449); mRNA 63 STAT1 91kDa
KKtDiCi tυ; tarvs rsrtwwπs s similar to serinβ,/threonine erine/thre
Cfe,11720.1, A kinase 3S (LOC609432): XM 8466 onine
1 at 1,02£-O2 i.OOE+00 1.34 mRNA 89 STK35 kinase 35
PREDICTED: Cams familiaris siwiiβr to Dual specificity protein phosphatase 24 (Map serine/thre kinase ptiosphatase-like onine/tyro protein MK-STYX; (DkOl sin specWoty phosphatase e
Cfa.174QQ.1.S inhibitor MK-STYX); transcript XM 8531 interacting 1 s at 9,89£-02 i.OOE+00 0.7 variant i (LOC4S8817); mRNA 19 STYXL1 like 1 succinate-
CoA
PREDICTED: Carns familiaris lipas simllar to succinate<oA ligase; e,
CfeAffx, 12646. GDP-forming; alpha subunit XM 5329 alpha
1.S1 s at 6,035-02 J.OOE+00 0 74 (LOC475775); mRNA 85 subuntt
99 Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
PREDICTED: C«rns familiaris similar to Siifite oxktese;
Cfa,11749.1,A mitochondrial precursor XM 5362 sulfite
1 at 7,63£-O2 i.OOE+00 0.74 (LQC48U03); mRNA 24 SUOX oxidase
PREDICTED: Can* familiaris simitar to Sulfite oxtøase;
CfaAHx.1103.1 mitochondrial precursor XM 5382 sulfite
,S1 at s.ioε-02 i.OOE+00 0.73 (LOC4SU03); mRNA 24 SUOX oxidase
PREDICTED: Cams familiaris similar to supβrviliin isofow S:
Cfe-Affx,β930,1 transcript variant 2 XM 8448
,S1 S at 2.2tε-02 i.OOE+00 0.63 (LOC477965); mRNA 07 SVlL supervillin
PREDICTED: Cams familiarls similar to supervillin lsoform 1;
Cfa.19132.1.S transcript variant 4 XM 8550 1 s at 4.56E-02 1.00E*00 0.7 (LOC47796S); mRNA 44 SVtL superviilin spectrin repeat
PREDICTED: Cams fartiiliaris containing similar to spectrin repeat containing; nudear envelope 2 , nuclear
Cfa.S691,1,A1 isoform e; transcrtpt ^anant I XM 5478 envelope
S.37E-O2 i.OOE+00 0.77 (LOC490729), mRNA L transfbrmi ng growth
Portιr>e mRNA for transforming
Cfa.4844.1.A1 growth factor-bets 3 (TGF- factor, at 1.29E-02 i.OOE-i-00 l.Sli bete 3) X14150 TGF83 beta 3
PftEDICTED: Can& familiars transform! similar to Transforming growth ng growth factor beta 3 precursor (TGF-
CfaAffx.26179. beta 3); transcript variant S XM 8631 factor,
1.81 s at 1.37E-O2 t.OOE+00 1.33 (LOC490796); mRNA 12 TGFB3 beta 3
Caπis lupυs famltiaris TM
CfaAffx,β6β1,1 mftNA for thrombomodulin; thrombom ,S1 s at 2.38E-O2 1.00EfOO 0.75 complete 5^5 AB 193481 THBD odulin
PREDICTED: Cams familiars similar to Transmembrane 4 transmem 16 family member i (Tumor- brane 4 L associated antigen t€) six fa (Membrane component; mily
CfaAffx.13216. surface markw J) (M3S1) XM 5343 TM4SF1 member
1.S1 s at 5.50E-O2 l.OOE+00 1.S7 (IOO177107); mRNA 02 8 18 transmem brane
BAX inhibitor
PREDICTED: Cams familiaris motif
Cfa.17747,13 similar to RECSl protein XM 8479 containing
1 s at 4.64E-O2 l.OOE+00 0.72 homolog (LOC610419); mRNA 23 TMBIM1 1 transmem brane
BAX inhibitor
PftEDICTED: Cams familiaris motif
Cfa.13654,1.A similar to R£CS1 protein XM 8479 containing
1 s at 3.B2E-O2 l.OOE+00 OJ^ homolog (LOC610419); mRNA 23 TMBIM1 1
KX) Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000102_0001
Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000103_0001
Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
Figure imgf000104_0001
Tabie 1:Genes Differentially Expressed in Adipose Tissue in Fa
PREDICTED: C«ms ftimsilaris simliai to ?mc fingw FvVfF domain containing protein 9 (Motfters against ctecapentapiegic homotog Interacting protein) (Ntedh- zinc Interacting protein} (Smari finger. anchor for receptor activation) FYVE {Receptor actfvatiαn anchor) (hSAWO (Novsi serine domain
CfeAffx.6587.1 protease) (NSP.. : transcript XM 5325 containing,
,S1 at 6.6«ε-02 i.OOE+00 1 33Jv3rtant i (LOC475352); mRNA 76 ZFYVE9 9
Bos tauαis zinc flrvger proteit\ 180; mfWA (cDNA done zinc fing MGC: lStS2S er
CfaAffx.7931,1 tMAGe:B097646), complete protein
,S1 s at 8.47E-02 i OOE^OO 0.75 OiS BC 149088 ZNF180 180
PREDICTED: Can& famlliatis zinc finger
CfaAffx.7983.1 similar to anc finger protein XM 8501 protein
.31 s at 7.11E-03 J.OOETOO 1.6^ 227 (LOC^S-MSO!, πiRtiA 12 2NF227 227 zinc finger
PREDICTED: Cam* familiaris
CfiaAfftc.26487. similar to zinc finger protein XM 8487 protein
1.61 s at 4.20E-02 t.OOE+00 0,«9 617 (L0C6110751; mMA 08 ZNF564 564
PREDICTED: Canis familiaris slrnllβir to zinc fingec protein zinc finger
Cfa.12414.1.A 622; transcript variant 2 XM 8632 1 s at S.90ε-02 1.00EfOO O 72 (LOC4793S3); mRNA 27 ZNF622 622
PREDICTED: Csnls familiaris zinc fing similar to zinc finger protem er
CfaAffx.29188, 622; tvanscf.pt vaπart 3 XM 8632 protein
1.31 s at 4.34E-02 2 OOEf OO 0.74 (LOC479383), ι«RNA 37 ZNF622 622 zinc finger,
SWIM-
PREDICTED: Cams familiatis tvp hypothetjcai IOC-579S17; e
Cfa.1177S,1.A transσipt varfsnt I XM 5366 containing
UL 8.46E-O2 l.OOE+00 0.73 {LOC479517); mRNA 2SWl M7 7 zinc finger,
SWIM-
PREDICTED: Cani* familiaris hvpOthetκai LOC479S17; type
Cfa.11779.1. A transcript variant 1 XM 5366 containing
1 s at a,osε-θ2 i.OOE+OO 0 72 (UX479517); mRNA 55 2SWIM7 7 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000106_0001
PREDICTED: CaniS membrane-
CfaAffx.14 farmliaris simitar to axobophm; toanscrlp* associated 897.1.S1 a vβnsnt l (LOC478763); .<S!V!....g???.g ring finger t 5.QSE-CB 1.776-02 0 75 mRNA 29 7-Mar (C3HC4) 7 famillarts similar to Septm- 2 (NEDD5 pixitein
Cfe.10982. homolog) (LOC4878δδ); .6M 2J3,2 1.A1 at 5.26E-03 1.79E-O2 0.7J mRNA 1$ 2-Sep septin 2
CfaAffx,20 famillarts similar to Sepferv 2 {NEDD5 protein 073.1.51 S iHimolog) (LOC48?8βδ); XM 8468 at 5.48E-CW l,02E»02 0.76 mRNA 16 2-Sep septin 2
CfaAf{χ.3O
Cams lupus familiaris 15 993.1,61 s kCW selenoprotein NM 0011 15 kDa at 9.846-04 1.16E-O2 0.73 (SEP15); mRNA 14760 15-Sep selenoprotein
CfaAffet.30 tiomo sap:ens is κt>a sel-flopfotein (SEP15); ■■ 1.31 S trsnsCTip* variant 2; NM 2033 1S kDa at S.2SE-03 ϊ.iaε-02 0.73 mRNA 41 15-Sep selenoprotein aminoadipate- s
PREDICTED: Pan emiaidehvde troglodytes aminoadipβte- dehvdrogenas senύaldehyrte Sz detiyarogenase- phosphopantβ phosphopaπtβtneinyl
Cfa.2510.1 transferase (AASOHPPT); XM 5087 AASDH theinyl
,S1 at ?..82eO3 IΛ&Έ-OZ 0,74 mRNA 34 PPT transferase famtliaris similar to ATP- birsdmg cassette subfamily E m«mber 1 ATP-bindinq trWasβ L inhibitor) cassette, sub(Ribonudease 1I inhibitor) fa (RN541): transcript mily E
Cfa.19800, variant 1 (LOC47S4S4); XM 5326 (OABP),
1.S1 s at 2.28E-05 7,55E-OJ 0.7 mRNA 79 ABCE1 member 1
PREDICTCD: Cams farmliaπs similar to ATP- bιnd-πg cassette; sub- ATP-bindino fanύly F; rttemlXN 1 (ATP cassette, subbinding cassette 50) (TNf fa alpha sδmuiated ABC mily F
CfaAffx,15 protesπ) (LOC47482δ): XM 5320 (GCN201 56.1.S1 at I.9OE-02 3.076-02 1.47 mRNA 56 ABCF1 member 1
PREDICTED: Cams
CfaAffx.27 familiarts similar to slpha/fctetβ hydrolase abhvdrolase 934.1.S1 s domain containing protein XM 5373 domain
2.θie-oj 1.48E-0. 0.7 3 {LOC480177); FI»WA Ql ABHD3 containing 3 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000107_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000108_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000109_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED- Cants A kinase
CfaAffr,27 I familiβriε similar to A- (FRKAΪ kinase anchor protein 10 724.1. S 1 ai precursor (LOC60907J); XM 6462 anchor protein t 3.66£-03 1.616-02 0.77 roRNA 74 AKAP10 10
PREDICTED: Cams aldehyde familiaris similar to d pyrfcxine- S carboxySate ehvdrogenas
Cfa.2653.1 synthetase isoform i XM 5349 ALDH 18 e 18 family,
.S1 at 2.4eε-03 1.41E-02 0.7<? (IOO177781); mRNA 76 A1 member A1 aldehyde,
PREDICTED: Cams d fβmtϋaris similar to ehvdrooenas
Cfa.403.1, arφquipn (LOC4S1486); XM 5386 ALDH7A e 7 family. A1 at 6.096-03 1.S8E-O2 0.67 mRNA 07 1 member A 1 aldehyde
PREDICTED: Cams familiaris similar to dehydropenas
Cfa.403.1. antiquitin (LOC481436); XM 5386 ALDH7A e 7 family. A1 s at 6,52E-W 1.06E-02 0.72 mRNA 07 1 member A1 asparagine- linked glvcosylation
PREDICTΕD: Equus 11 homoloq caballυs βsparagine-linked (S. cerevisiae, glycosytation 11 homotog aipha-1 ,2- (S. cerevisiae: alpha-! ; 2-
Cfa.11280. mannosyitfansfefβse) XM 0014 mannosyltrans
1.A1 s at 6.62E-03 1.94E-02 0.72 [AlQIi); mRW 87974 ALG11 ferase) asparagine- linked glycosylation 5 homolOfl (S, pREDiαeo: canis cerevisiae, farmliaπs sirn'tar to dolichyl- Doildiyi-ptiosphate beta- phosphate glueosyitransferase (DoϊP- b gluccsyitrarssterase); eta-
Cfa.16818. tf adscript variant S XM 8518 alucosyltransf
1.S1 s at 5.1SE-04 1.016-02 0.7 (LOC477301); mRNA 76 ALG5 erase)
CfaAffx.26 ftimiliaris similar to ankyrin repeat domaln
557.1.Si s 12; transcript variant 2 XM 8544 ANKRD ankyrin repeat at 374E-04 9.61E-03 0.73 tLOC4δQ2Q5); mRNA 53 12 domain 12
CfaAffx.12 PREDICTED- Osπls famiiieris similar to 205.1.Si s ankynn repeat tiomain 37 XM 5328 ANKRD ankyrin repeat at 2271-02 3.33E-O2 0.75 (LOC475627), mRNA 41 37 domain 37
PREDICTED- Osπls faniilisris similar to
CfaAffx.44 ankynn repeat domain 39 XM 5317 ANKRD ankyrin repeat 52.1.S1 at LOiE-04 8.90E-03 0.64 (LOC47456S), mRNA 96 39 domain 39
PKEDTCTSDrCams farmllaris similar to fetal
CfaAffx,71 globin inducing factor XM 5422 ANKRD ankyrin repeat 46.1.S1 at i.446-03 1.25E-O2 0.77 (LOC48512S); mRNA 43 49 domain 49 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
acidic (leucine' rich) nuclear
Cams familterte inhibitor-, phosphoprot of protein phosphatase ei
Cfa.31.1.S type 2A mRNA; complete n 32 family, 1 s at ..946-02 3.11E-O2 AY162293 ANP32A member A
PREDICTED: Cams familiaris similar to Arπexin A3 (Annexin UI) (Lipocoitit) IH) (Placenta: sntScoaguSant protein III) (PAP-HE) (35-alpha
CfaAffx.13 calcimed'n) (Inositol 1;2- cydic phosphate 2-
980.1.S1 al phosprtortydrolase) XM 5356 t I.95E-02 a.itε-oa 0.7 (LOC478447), mRNA 24 ANXA3 annexin A3
PREOlCTED. Cams familiaris similar to Annexifi AS (Annewi V) (Upocortn V) (Enctonβxm H) (Calphobindin I) (CSP- F) (Placental anticoagulant prøt«n J) (PAP-I) (PM) (Thromboplastin inhibitor) (Vascular anticoagulant- alpha) (VAC-afpha)
Cfa.12149, (Anthorin at) XM 5333
LSI at 7.036-02 6.17E-02 0.76 (LOC-1760M); mRNA 03 ANXA5 annexin A5
PR6DICTED-. Canls familiaris similar to amine amine oxidase oxidase (flavin containing) (flavin domain 2 ssofonn a;
Cfa.229.1, transcript variant 2 XM 8615 containing) S1 at I,39£-02 2.66E-02 0.75 (IOC47S193); mRNA 17 AOF2 domain 2
PREDICTED: Cams familiaris similar to adaptor- adaptor-related protein related protein complex l; gamma 1 co subuπit isoform a; mplex 1 ,
Cfa.10636. transcript variant 3 XM 8574 gamma 1
1.S1 s at 4.9Sε-03 1.76E-02 0,77 (LOC47%66); mRNA 37 AP1G1 subunit familiaris similar to Adaptef-reiated protein complex 3 mu 1 suburnt adaptor- (Mυ-adaptm 3A) (AP-3 r adapter conψiesx mα3A elated protein
Cfe.1576S. subunit) (LOC4890S2); XM 5461 complex 3.
1.A1 at i.πε-03 1.2OE-O2 0.76 mRNA 70 AP3M1 mu 1 subunit familiaris sirn'Uir to Adapter-teiated protein complex 3 mu J suburdt adaptor-
CfaAffx,23 I (Hu-adaptm 3A) (AP-3 r adapter tompiex mu3A elated protein 575,1, S1 ai subunit) (LOC489052); XM 5461 complex 3, t i Ϊ.94E-04 9.06E-03 0.72 mRNA 70 AP3M1 mu 1 subunit
Can»s familβπs heat
Cfa.1256,1 shock protein ApCrZ (Apg heat shock ,A1 S at 1.80E-03 l,30E»02 0.7S Z) mRNA; complete αis AY911512 APG-2 protein Apg-2
UO Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Cants familiars heΛ
Cfa,63β2,1 shock protein Apg-2 (Apg- heat shock
.A1 at 2.92E-02 3.80E-O2 l.Η 2} mSNA; complete cds AY911512 APG-2 protein Apg-2 famillaris similar to
CfaAffx,15 smytoki beta (A4) amyloid beta precursor-like protein 2; 873.1.S1 s transcript variant 23 XM 8516 (A4) precursor at l.SOE-02 2,75£-02 072 (LOC479393); mRNA 42 APLP2 like protein 2
Cfe.3891,1 Dog apollpeprotsin C-HI apolipoprotein ,S1 at 2.S8E-03 1.44E-02 1.4 mRNA; complete cds M17178 APOC3 C-Hi
Cfa.3891.1 Dog apollpoproϊeirt C-HI apolipoprotein ■S1 x at 103E-02 2.33E-02 1.31; mRNA, complete cds M17178 APOC3 C-III amyloid beta precursor
PREDICTED: Pan protein troglodytes amytotø beta (cytoplas precursor protein-binding mic
Cfa.2457,1 protein 2 (Af>f>8P2); XM 001 1 tail) binding .S1 at 3.04€-02 3.88E-O2 0.76 mRNA 36633 APPBP2 protein 2
FKeEJICTεDT tSniS aquaporiπ 3 faniiliaris similar to
Cfe.21549. Aquaporin 3 XM 8495 (Gill blood 1 S1 s at 7.17E-02 6.24E-02 0.72 (LOCδπ?92), mRMA 03
CfaAffx,25 ' PREDICTHTCanir familiarts similar to
331.1, S1 al aquapofin 9 XM 5447 I I 3.36£-02 3.39E-02 0.69 (LOC487576); mRNA 01 AQP9 aquaporin 9
CfaMxAQ PREDICTCD: Cams ADP- farmliarts similar to AOP- 64.1.S1 S libc5y!ation factor 1 XM 5318 ribosylation at a.sβe-03 1.56E-02 0,77 (LOC474S91); mRNA 20 ARF1 factor 1
HcHiio sapiens AOP- ADP- αa.2289.1 ribosyiatton factor 6 NM 0016 ribosylation .S1 at S.39E-02 5.31E-O2 0.76 (ARBS); mftNA 63 ARF6 factor 6
PREDICTED.' Cβnis ADP- famϋlaris similar to ADP- ribosviation ribosyiabon factor GTPβse factor GTPasβ scttvatirsg protein 3;
Cfa.10772. transcript variant 5 XM 8523 ARFGA activating
1.A1 at i.ooe-03 l,t7E-O2 0.74 (LOC474477); mRNA 21 P3 protein 3
PREDICTED: Cams ADP- famϋiaris sirn'lar to AOP- ribosyiation rtbosyiatlon factβf GTPase factor GTPasβ activβtJng protein 3;
Cfe.17093. transcript variant S XM 8523 ARFGA activating
1.S1 at i.ioε-03 1.206-02 0.71! (LOC4744??), mRMA 21 PJ protein 3
PREDICTED: Canls ADP- familisris similsr to ADP- ribosyiatioπ
CfaAfix.23 ribosyiation factor GTPase factor GTPas activate protein 3; e 27.1.51 s transcript variant 5 XM 8523 ARFGA activating at 4.266-05 7.55E-O3 0.67 (lOO»7<W77); mRNA 21 P3 protein 3 familiarts similar to AT AT rich
CfaAfix.17 rich Interactive domain 48 int βoform 1; transcript eractive 840-1.S1 s vβiisiΛ 3 (LOC4883S9), XM 8436 domain 4B at 2.38E-02 3.41E-02 0.73 mRNA 23 ARIP4B (RBP1-like)
U l Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
faniiiiaris similar to At AT rich
CfaAffx,17 rich interactive domain »18 int isoform i; transcript eractive 879,1, S1 S variant 3 (LOC4S8959); XM 8436 domain 48 at 2.82E-02 3.72E-02 0.76 ITiRNA 23 ARID4B (RSP 1 -like)
PREDICTED. Cams
CfaAffx.11 famlllarls similar to AOP- ADP- ribosyiation factor-like l; 375.1. S1 s transcript variant 1 XM 8478 ribosylation at i.soe-03 1.23E-O2 0,73 (LOC612931), niRNA 97 ARL1 factor-like 1
ADP-
PREWCTED: Cams ribosviatioπ- familiaris similar to ADP- lik ribosyiation factoi -like 6 e factor 6
Cfa.20059, Interacting protein 5 XM 5337 ARL61P interacting
1.A1 at i.366-03 1.23E-O2 0.7S (10O176S59); mRNA 64 5 protein 5 repeat containing 1; roWlA (cDNA clone ar MGC.127965 madillo
Cfe,1737,1 IMAGE.7954315); repeat
,A1 at 4.56E-03 1,726-02 0.72 comptete cds BC103407 ARMC1 containing 1 armadillo
CfaAftx.27 PREDICTED: Canls r familiaris similar to ALEX3 epeat 095.1.Si s protetπ (LOC492022); XM 5491 ARMCX containing, X- at i,77E-04 9.006-03 0.73 mRNA 42 linked 3
PREDlCTED: Cams arqinine-rich. familiaris similar to ARMET protein precursor mutated in
Cfa.20824. (Arginlne-rlch protein) XM 8454 early stage
LSI at 2.5OE-03 1.43E-O2 0.74 (LOC608421); mRNA 47 ARMET tumors actin related
PREDICTED: Cams protein 2/3
CfaAfftc.23 I familiaris similar to actm co related protein 2/3 mplex, 231.1.81 al camptex subunit IA XM 5368 subunit 1A, t 3.2βε-03 l.SSE-02 (LOC47974S); mftNA 73 41kDa familiaris similar to actin actin related retated protein 2/3 prot comptex; subunit 5-iike; ein 2/3
Cfa.17137. transαipt variant I XM 8462 complex,
1.81 at 6.68E-04 1.O7E-O2 0,74 (LOC612SS6); mRNA 53 ARPC5L subunit 5-like familiaris sιrrκtar to actin actin related
CfaAffx.30 nslatsd protein 2/3 prot comptex; subunft 5-llke; ein 2/3 958.1.S1 s transcript variant 2 XM 8584 complex, at I.66E-03 l.286-0a 0.67 (UX:6S2S56); mRNA 38 ARPC5L subunit 5-like
PREDICTCD: Cams fifc fβmillarts similar to N- acylsphinqosi scyisphirsgosine ne am«tohydro;as« (acid a ceramidase) 1 midohvdrolas
Cfe.1326.1 pwproprotesn isoform a XM 5400 e (acid ■S1 at 9.63E-02 7.42E-02 0.72 (UX432S97); mRMA 12 ASAH 1 ceramidase) 1
Arao;cop£(s maϋana unknosvn protein
Cfe-Affx.50 (AT3GUS10) mftNA; NM 1121 AT3G13 hypothetical 53.1.S1 at 4.636-02 4.S8E-O2 1.37 comptete cds 97 510 protein Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDlCTgD: OmIS ATPase familisris similar to tw> family. AAA AAA domain containing
CfaAf&c,23 protein; transcript variant XM 8454 domain 90.1.S1 at Ϊ.SSE-03 1.26E-02 Q.65J2 (LOC475090); mRNA 27 ATAD2 containing 2
ATPase fa
Homo sβpiens mRNA for mily, AAA
Cfa.16352, KiAA12<»0 protein; partial domain
LSI at 1.45€-02 2.7OE-O2 0.75 αfs AB033066 ATAD2B containing 2B
PREDICTED. Cams fβmiliaris similar to ATG5 Autophagy protein 5-like autophagy (APGS-IAe) (Apoptosis- r speciflc protein); elated 5
Cfa.3397.1 trβnscnpt variant 1 XM 8492 homoloq (S,
,A1 s at 6.36E-03 1.91E-02 076 (LOC61036S); mRNA 01 ATG5 cerevisiae)
PREDICTED; Cams famϋiaris similar to ATG5 Autophagy prcrtein 5-llke autoohaαv (APGS -like) (Apoptosis- speαfic protein); related 5
Cfa.3397,1 tf adscript variant 3 XM 8632 homoloa (S.
.A1 at 4.32E-03 1.68E-02 0.74 (LOC6I0868); mRNA 88 ATG5 cerevisiae)
Homo sapiens cDNA
CfeAfix.18 I PUS6374 complete cds; higπiy similar to Probable 231.1.81 al phospholipid-transporting ATPase. dass t 3.94€-04 9.61E-O3 0.7 ATPase IF(EC 3.6.3 Ii AK304855 ATP118 Vl. type 1 tB famtliaris sitnilar to Potentiai phospholipid- trsnsportmg ATP9se IP (ATPase class ϊ type 118)
Cfa.19636, (ATPase IR) XM 5358 ATPase, class
1.S1 s at 9.J-K-06 6,68E-OJ 0.73 (LOC47S64t); mRNA 16 ATP11B Vl. tvpe HB farmlians similar to Potentiai phosphollpid-
CfaAffx.16 trβnsport)ng ATPase IF (ATPase class I type UB) 234.1, S 1 s (ATPase IR) XM 5358 ATPase, class at S. IS E-OS 877E-03 0.72 (LOC<t78644); mRNA 16 ATF11B Vl. tvoe HB
PREDICTED: Cams ATPase, familiaπs similar to Ca++ calcium-transportfng transporting. ATPase 2Cl lsoform Ia;
Cfa.19006. trsnswipt variant 12 XM 8587 type 2C.
1.S1 s at 10SE-02 2.37E-02 076 (I.OC477066); mRMA 40 ATP2C1 member 1
PREDICTED. Cams ATPase. famlllarls similar to Ca++
CfaAffx.10 i calcium-transportirig transporting. ATPase 2Cl isoform is; 126.1.51 ai transαipt vailant 12 XM 8587 type 2C, t 6.16£-(M l.OSE-02 0.75 (LOC477066); mRhU 40 ATP2C1 member 1 familiaris sirrsilar to ATP ATP synthase. synthase; H r transporting; ML mitocriondrsal Fl transporting, complex; gamma subunit mitochondrial isofofm H (heart) F1 co precunei; ϋanscript mplex,
Cfa.990.1. vβnsnt 1 (.00478009); XM 5351 gamma SI s at S.S7E-06 6.68E-03 0.73 m«NA 93 ATP5C1 polypeptide 1 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000115_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
familiaris stmilar to bromodomaiπ adjacent to bromodomain
CfaAffx,2Q zinc hn^ef domain; IA adjac tsoform s; transcript ent to 602.1. S1 s variant 9 (LOC460287): XM 8566 zinc finger at 4.68£-03 1.73E-02 0.74 mRNA 78 BAZ1A domain. 1A famtliaris similar to Sβrctet Biedi syndrome 7 protein tsoform b; transcript
CfaAffx.71 vsrnnt 4 (LOC4760S2); XM 8521 Sardet-Siedl
03.1.S1 at 2.90E-02 3.78E-02 0.77 mRNA 28 BBS7 syndrome 7
PREWCTED: Cams familiaris similar to B-CfHi B-cel) receptor receptor-associated
Cfa.20742, protein BAP29 lsoform d XM 5330 associated
1.S1 s at 5.326-02 5.28E-O2 0.73 (LOO»7S8δ4); mRNA 92 BCAP29 protein 29 famiiiaris similar to Breast carcinoma amplified sequence 2 homoiog bieast. (ONA ampiified in carcino mammary carcinoma- 1 ma
CJa.3943.1 protein) (LOC475S05); XM 5330 amplified
-A1 a at 8.$<tε-03 2.20E-O2 0.73 ΓΛRNA 14 BCAS2 sequence 2
PREDICTED: Cams farmliarts similar to 8cl-2- relatβd protein Al {BFl-i
CfaAfftt,21 protein) (Hemopotettc- specWc eariy response 575.1.Si s protein) (GRS protein) XM 5458 BCL2-related
2.SSE-02 3.7J6-02 0.7S (LOC4S8770), mRMA BCL2A1 protein A1
B double prime 1 , subunit of RNA
PREDICTED-. Cβπls polymerase familiaris similar to transcription transcription factor-fike
Cfa.11173, nuclear reguiator XM 5352 initiation factor
1.A1 s at 4.27£-02 4.67E-02 0.73 (LOC478090); mRNA 87 BDP1 IHB
PREDICTED: Cams familiaπs similar to Biliverdiπ reductase A precursor (Bi!lveιdln-IX
Cfa.10514. aipha-i'βtiuctase) (SVR A) XM 5330 biliverdin
1.S1 at 1.S2E-03 1.28E-02 0.76 (I.OC475S67); mRMA 75 BLVRA reductase A
Cfa.1316S. family protein partial XM 0019 Bm1 44 PHD-fmoer 1.A1 s at 2.13E-02 3.246-02 0.75 mRNA 005 family protein
PREDICTED: Canis ftimiliaris sitnilar to Cytoplasmic tyτo-Jne- protein Kinase 9MX (Bone marrow tyrosine kinase gene In chromosome X BMX non-
CfaAffr.18 protein) (EprtfreOal and endothelial tyrosine receptor 770-1.S1 s kinase) (ETK) (NTK38) XM 5488 tyrosine at 3.4SC-02 4.16E-02 0,76 (LOC4917S0); mRNA 70 BMX kinase Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
BCL2/adenovj rus EIB
CfaAffx,25 19kDa 505.1. S1 s 80s iaunis cDNA clone interacting at ?..4ε-(M 1.08E-02 0.72 IMAGE.8094530 BC148951 BN1P2 protein 2
PREDICTED-. Osπls familiaris similar to 3(2);S bisphosphate rejcteotidass 1 (Sissphosprtate 3- nucteobdsse 1) (PAP- loosιtol-l;4- phosphatase) 3'<2'). 5'-
Cfa.11221. (PlP) (LOC60SS2S); XM 8455 bisphosphate
1.A1 at 3.976-04 9.61E-O3 0.67 mRNA 76 BPNT1 nucleotidase 1
CfaAHx.15 PREDICTED: Canis fβmiliaris similar to 480.1, S1 s bromodomβin containing XM 5353 bromodomain at 4.83E-03 1.75E-O2 0.72 7 {IOC47S130}; mRNA 06 BRD7 containing 7 brain and
PftEDICTED: Cams reproductive famtllarts similar to brain oioan- and reproductive orgari- express expfess«d protein; ed
Cfa,14120. transαipt variant 1 XM 5329 (TNFRSF1A
1.A1 s at 1.88E-02 3,0«E»02 0.74 (LOC4757U); mRNA 18 BRE modulator)
PREDiαED: Canis farwlians similar to Brain
Cfa.10573. protein U (pRGRJ) XM 8460 brain protein 1.A1 at 1.43E-02 2,70E»02 0.7S (LOCS08902); mRNA 53 BRI3 I3 familisris βimilsr to Brasn
Cfa-13282. prot«n 44 (LOC480086); XM 5372 brain protein LSI s at 2.9SE-04 9.2SE-03 0.73 mftNA 09 BRP44 44
PREDICTED. Cams famϋlaris similar to Biain protein 44-hke protein;
Cfa.11093, transσipt vsrisnt 5 XM 8580 brain protein
1.S1 at 1.076-04 8.9OE-O3 0.76 (LOCSO9356); mRNA 18 BRP44L 44-like
PREDICTED: Cams aaASfx.22 familiaris similar to βrain protein 44-like protein; 7.1.S1 s a trsnscript variant S XM S580 brain protein t 4,S2E-04 l.OOE-02 0.75 (.OCS09356); rrsRMA 18 BRP44L 44-like
PREDICTED; Cams BTAF 1 RNA farmliaris similar tc TATA- polymerase II. biwiing-protein- B-TFlID associβted factor 172 (TSP-assocmted factor transcription 172) (TAF-.72) factor- (TAf={π)170) (B-TFJlO associated.
CfeAffx.11 I trartsσipfcσπ factor- βsscctatecl 170 KDa 17OkDa (Mot1 934.1, S1 al subunlt) (LOC4SδβOO»; XM 5439 homoloo, S. t 1.14C-03 1.20E-O2 0.7 mSMA 29 BTAF 1 cerevisiae)
PREDICTED-. CΛΠIS Bruton familiaris similar to Brutors aaammaolobu a5ar!irna<)lobulifwmla tyrosine kinase; transcript linemia αa.16454. variant 6 (LOC492019); XM 8566 tyrosine
LSI at 6.43E-02 5.87E-O2 0.77 mRNA 82 BTK kinase
I fό Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
CfaAffet.23 farrnllaris similar to 610 BUD31 protein homoiog (EDG-Z); 181.1.S1 x transαipt valiant 1 XM 5368 hαmolog (S, at 3.14E-03 1.S3E-O2 0.76 (LOC479743); mRNA 71 BUD31 cerevisiae)
KWIUTκD7v3π]5 familiaris similar to RNA
Cfa.673.1. processing factor i XM 5370 brix domain S1 at S.07E-03 2.21E-02 0.7 (LOC'17θθ72); mRNA 96 BXDC5 containing 5 farmliaiis similar to RNA
Cfa.673.2. piocessing fectoi I XM 5370 biix domain S1 s at 6.08£-03 1.88E-02 0.77 (LOC479972); mRNA 96 BXDC5 containing 5 complement
Cfa.3834.1 Cfamilsarø mRNA for component 5a
.S1 at 9.3i£-D2 7.27E-O2 0.76 αsmplernβnt CSa receptor X65860 C5AR1 receptor 1 chromosome
CfaAffx.13 PREDICTED: Bos taiirus 12 open ctsromosome 12 open 131.1.S1 s reading frame 62 orttiolog XM 0012 C5H12O reading frame at 6.726-03 1.95E-O2 0.72 (C5H12off62); mRNA 50167 rf62 62 OfthOlOQ
Homo sapiβrø chromosome chroπtosome 5 opβfi 5 op reading frame 33 en
Cfe.4155.1 (CSorf33); transcript NM 1530 reading frame
.Ai at 5.26C-02 S.2SE-02 0.76 variant 2; rrtRNA 13 C5orf33 33
Bos taurus chtomosome 5 open leading frame 15 chromosome orthotog: mRNA (eDNA 5 open clone MGC: 127320 αa.240.1. IMA6e:7948βS3); C7H5O reading frame AJLat I.SOE-02 3.00E-O2 0.77 compete cds BC 102841 RF15 15 oi1holOQ
Homo sapiens chromosome 7 open chromosome reading frame 23; mRNA 7 op (cDNA clone MGCM7S en
Cfa.18190. IMAG£:3634983); reading frame 1.S1 at 3,346-03 I.S66-02 0.76 wmptete ette BC002837 C7orf23 23
PREUICTEDTPari calciu trogkxiytes caicium m
Cfa.3420.1 bind'πg protein 39 XM 5260 Λjjt 4.53E-03 1.71E-02 0.76 (CAB39); mRNA 55 CAB39 protein 39 farwlians similar to
CfaAffx.16 C«ιic!um binding protein 39 (Mo2S protein); calcium 790.1.Si s transcript variant 4 XM 8560 binding
4.S8E-02 S.036-02 0.76 (LOC477403), mRMA 13 protein 39 fanύliaris similar to calreticulln; transαlpt
Cfe.4277,2 variant 1 (100)76694); XM 5338
MJL 5.9SE-0S 8.40E-03 0.75 mRNA calreticuHn i' Mac i 't,'o '."cenTs**"* familiaris similar to calυmenln precursor;
Cfe.3402.1 transcript variant 4 XM 8535 ■S1 at 2.11E-03 1.36E-02 0.77 (UX475201); mRMA 21 CALU calumenin
CfaAffr.33 familiaris similar to calumenin precursor; 75.1.S1 S transcript variant 4 XM 8535 at 3.6SE-0S 7.SSE-03 0.74 (LOC475201), mRI^A 21 CALU calumenin Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000119_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Canis coil familiaris similar to Ϋrvsr ed-coH
Cfa,10657. protein iong lsoform XM 5358 domain 1.A1 at 3.38C-03 1.S6E-02 0.75 α<X47S6?5); mRNA 44 containing 50
CfaAffx,25 famillaris similar to coil Protein AD-016; transcript ed-coil 466.1. S1 s variant t (LOO475444); XM 5326 domain at 2.ΗE-CW 9.06E-03 0.66 mRNA 68 containing 53
KKtUIl-I tU.' WIOiS coil famlllarts similar to ed-coil
Cfa.9407,1 CG15881-PA; isoform A XM 5357 ■A1 s at 9.35E-04 1.16E-O2 0.7S (IOOJ7SSS3); mRNA 59 containing 56
PREDICTED. Cams famillaris similar to coiled- coiled-coil
Cfa.14257, coil domain containing S XM 5415
1.A1 at 6.9SE-05 8.42E-03 1.32 {IOC1&Η30); mRNA 45 CCDC8 containing 8
CfeAffx,29 familiaris similar to cyciin L2 isofoπn 1; transcript 399,1, S1 S variant 3 (LOC479570); XM 8434 at i.wε-02 2.42E-O2 0.73 mRNA 60 CCNL2 cvclin L2 familiails similar to Ce(S
CfaAffx,24 i cycJe progression 1 isoform 2; transcript 405.1. S1 ai variant 3 (LOC487S66): XM 8584 cell cycle
L 5.17E-03 1.79E-02 0.67 mSNA
PREDICTED: Canis m progression 1 familiaris similar to chaperonin
CfeAfix.76 chapeiwiin containing containing TCPl; subumt 3 Isoform 95.1.S1 s c; transcript variant 3 XM 8591 TCPL subunit at i.84€-03 1.31E-O2 0.7<? (LOC480123); mRNA 72 CCT3 3 (gamma)
PREDICTED-. Caπls famiiiβris similar to T- chaperonin complex protein 1; deita containing subunit (TCP-I -deita)
Cfa.1588.1 (CCT-de!ta) (A45) XM 5393 TCPl . sυbuπit
.S1 at 3.31E-03 1.55E-O2 0.76 (LOC4S2.71); mRMA 90 CCT4 4 (delta)
PREDICTED: Canis familiaris similar to T- chaperonin complex pfotein 1; deita containing sυbυnft (TCP-I-βεita)
CfaAffx.55 (CCT-oeiU) (A45) XM 5393 TCPJ. subunit 72.1.S1 at 2.6«ε-os 7.556-03 0.76 (LOC4S2271); mRMA 90 CCT4 4 (delta)
PREDICTED: Cams familiaris similar to T- chaperonin
CfaAfTx,S5 comptβx protein 1, deitβ containing subuπlt (TCP-I -delta) 72.1.S1 s (CCT-deita) (A45) XM 5393 TCP1, subunit at 9.87E-0S 8.90E-03 075 αθC4S22?J); mRMA 90 CCT4 4 (delta) familiaris similar to T- complex protein 1; chaperonin epsiion subun« {TCP-l- containing epsiiors) (CCT-βpsilon1):
Cfe,18708. transcript variant 1 XM 8432 TCP1, subunit
1,81 S at 7.4SE-CW l,09E»02 0.7li (LOCS06373); mRNA 10 CCT5 5 (epsiion) famiiisris similar to T- comptex protein 1; chaperonin
CfaAffr.15 epsϋon subunit (TCP-S- containing epsiion) (CCT-epsilon); L1.S1 s transcript variant J XM 8432 TCPL subunit at 3.60e-04 9.61E-03 0,73 (LOC6O6873); mRNA 10 CCT5 5 (epsiion) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000121_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000122_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000123_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000124_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000125_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED-. Cants coatomer famiiiβris similar to protein coatomer protein co complex, subuπft bete 2 mplex,
Cfa.1S764. (beta prime) XM 5342 subunit beta 2 1.S1 s at 8.28E-05 8.776-03 72 (LOC47708S); mRNA 83 COPB2 (beta prime)
PREDICTED. Cams coatomer fβmiliaris similar to firoteifl coatomer protein co complex; subunit beta 2 mplex,
Cfa.20115. (beta pπme) XM 5342 subunit beta 2 1.81 s at 4.896-03 1.75E-O2 0.73 (LOC4770S8); mRNA 83 COPB2 (beta prime)
PREDICTED: Canis coatomer farmliaris sirn'tar to protein coatotriet protein co comptex; subunit bete 2 mplex,
Cfa.3255.1 φeta prime) XM 5342 subunit beta 2 ,A1 s at 8,0OE-(M l.Xøε-02 0.70 (U5C477080), mRMA 83 COPB2 (beta prime)
PREDICTED: Cams coatomer familiariδ similar to protein
CfeAffx.12 coatomer protein co complex; subunit beta 2 mplex, 255.1, S1 s (beta prime) XM 5342 subunit beta 2 at 2.3δE-03 1.40E-02 0.7 (LOC477088); mRNA 83 COPB2 (beta prime)
COP9 constitutive
PREDICTHD: Csnls photomorphog famιliari5 similar to COPS signaiosome subunit 4; eπic homoloq
Cfa.2267.1 transcript variant 2 XM 8541 subunit 4 .S1 s at 3.69£-04 9.61E-03 0.73 (LOC47S4SS); mRMA 95 COPS4 (Arabidopsis)
PREDICTED: Cams famillarls similar to COPθ agnaiosom* compiex subunit 5 (SJgnaloβome subunit S) (SGN5) (2m COP9 aeBvatioo domβln-bindlng constitutive protein 1) (K)pi C- photomorphog termifius iπtaracting protein 2): tanscript enic homoloq
Cfa.11305. variant 1 (LOC477901); XM 5350 subunit 5
1.At s at 3.936-04 9.61E-O3 0.7_ mRNA 93 COPS5 (Arabidopsis) coenzyme Q3 homolop,
PREDICTED. Cams methyltransfer
Cfa.19331. familiarls coenzyme QS XM 5322 ase (S, 1.S1 at ..62E-02 2.856-02 0.76 (COQ3); niRNA 41 COQ3 cerevisiae)
PREDICTED.' Cams famiilaris similar to co O530493-P6; traoscnpt enzyme Q9
C88.1S15.1 variant t (LOC47SU0): XM 5352 homolog (S. ■A1 at 7.54€-03 2.C4E-O2 0.73 mRNA 84 COQ9 cerevisiae) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
COR1P2 olfactory receptor
CfaAffe.29 Cams lupus familiaris iP2 family 1 olfactory receptor protein S03.1.S1 a (ORi n) mRNA; complete subfamily P- t 2.516-03 1.436 02 1.31 cds Ef 451962 cOR1P2 like
Figure imgf000127_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000128_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000129_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000130_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000131_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000132_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famiiiBrts similar to Deri- like domain famϋy; D member 2; transcript er1-like
Cfa.3368,1 variant 1 (LOC6O6991); XM 8432 domain family,
,S1 at 4.9SE-03 1.75E-02 0.73 ITiRNA 61 DERL2 member 2 fβmiliaris similar to Dw-I-
CfaAffx.23 l like domain family; D member 2; transcript eri-like 819.1. S1 ai variant I (LOC608991): XM 8432 domain family, t 3.826-03 1.4SE-02 0,77 mRNA 61 DERL2 member 2 fβmiliaris similar to Putative pre-mRNA splicing factor RNA DEAH (ASP- hetase (OEAH box Glu-Ala-His) protein 15), transcript
Cfe.11317. variant 9 (LOC488856); XM S589 box
1.A1 s at 5.27E-03 1.796-02 0.77 mRNA 70 DHX15 polypeptide 15
PREDICTCD: Cams DEAH (Asp- farmliaπs similar to OEAH GIu-AIa-HiS) (Asp-Glu-Ala-hfis) box
Cfa.2263.1 polypeptide 29 XM 5352 box
-A1 s at 4.26£-03 1.68E-02 0.76 (LOC478060); mRhU 38 DHX29 polypeptide 29 fβmillarts similar to disrupted in disrupted in renal
Cfa.1675,1 carcinoma 2 XM 5357 renal i.uε-02 2.40E-O2 0.75 (LOC478SSS); mRNA 64 DIRC2 carcinoma 2
DIS3 mitotic
CfaAffx.64 PR6D1CTED-. Canls control ramiiieris similar to 60.1.S1 s K!AA1008 (LOC485491}; XM 5426 homolog (S,
6,77E-(M 1.076-02 0.68 mftNA 10 DIS3 cerevisiae)
DIS3 mitotic control
PREDICTED: Cams ho famtliaris similar to molog (S.
Cfa.429.1. C66413-PA (LOC478346}, XM 5355 cerevisiae)- A1 at 2.67e-02 3.62E-02 0.75 mRNA 20 DJS3L IiKe dihydrolipoami
C«ιnis lupus famlliatis dihydrolipoamSde
Cfa.β62.1, dehydrogenase (DLD); NM 0010 dehvdrooenas SI s at I.7SE-02 2,956-02 0.69 mRfviA &
PR6D1CTED-. Csnls ftimiliaris sitnilar to Dimethylglycifw! dimethylglvcin
CfeAftc14 dehydrogenase; mitochondrial precursor
460.1. Si s (ME2GLYOH) XM 5460 dehydropenas at 6.18E-02 5.73E-O2 1.31! (LOC48893SJ; mRNA 52 DMGDH e
PREDICTED: Cams farmllaris similar to Dna3 homolog subfamily S membet 11 precursor (ER associated dna3 protein 3) (Er)3) (ER-βssociatec DnaJ (HSP40) Hsp40 co-cbaperone) ho (hDj9) (PWPl-mteractiπg moloq,
Cfa.20980. protein 4) (l0C47δ664); XM 5358 DNAJB 1 subfamily B.
LSI s at 1.49E-02 2.74E-0. 0.74 mRNA 34 1 member 11 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Canis famtHaiis similar to DnaJ DnaJ (HSP40)
CfaAffx,22 (Hsp40) homotog; homolofl, subfamily 8; member 12; 335.1. S1 s transcnpt variant 6 XM 8568 DNAJB1 subfamily B. at i.siε-02 2.7SE-02 0.67 (LOC4890Ϊ9); mRNA 92 member 12
PREDICTED: Pan troglodytes similar to DnaJ (Hsp40) Ona) (Hs|>40) homolog; ho subfamliy 8; member 14; molog .
Cfa.406.1 transσipt variant 3 XM 0011 DNAJB1 subfamily B±.
IUL 5.366-03 1.82E-O2 0.71: (IOC47.258); mRNA 67856 4 member 14 farroliaris similar to OnaJ DnaJ (Hsp40) (Hsp40) homotoς; ho subfamily 3; member 14 molop,
Cfa.10963. isoform 2 (LOC487875); XM 5449 DNAJB1 subfamily B, 1.A1 s at I.43E-03 1.2SE-02 077 mRNA 97 member 14 familiaris similar to DnaJ (H_p40) homolog: DnaJ (HSD40) subfamliy 8; memSef 6 homoloff, Isoform s; trarøcήpt
Cfia.3079,1 variant 3 (LOC608937): XM 8565 subfamily B.
-S1 at e.ssε-03 1.94E-02 0.76 mRNA 69 DNAJB6 member 6
PREDICTED: Canis DnaJ (HSP40) ftimiliaris sitnilar to Ona3 ho (H5JWG) homolog; moloα.
Cfa.17880. sυbf3mi)y B; member 9 XM 5325 subfamily B.
2.S1 s at i.lSE-03 1.21E-02 0.73 (UXT4752S6); mRMA 18 DNAJB9 member 9
PREDICTCD: Cams familiaris similar to OnaJ DnaJ (HSP40) αaAfix.22 (Hsρ40) homotog; ho subfamily C; member 10; molofl, 084.1.S1 s transcript variant 1 XM 5359 DNAJC1 subfamily C, at 5.87E-03 i.seε-o∑ 0.77 (_OC473S2δ); mRMA 88 member 10
PR6DICTED: Canls DnaJ (HSD40>
CfaAffr.10 faniiliaris similar to ho dopamine receptor moloα, 82.1.S1 s interacting protein XM 5316 DNAJC 1 subfamily C. at tπε-03 1.206-02 0.73 (LOC474392); mRMA 25 member 14
PREDICTED: Canls DnaJ (HSP40)
CfaAHx.10 familiaris similar to dopamine receptor homolog , 85.1.S1 s Interacting protein XM 5316 DNAJC 1 subfamily C, at 2.30E-02 3.35E-O2 0.69 (IOCW392); mRNA 25 member 14
DnaJΪHsD40)
PREDICTCD: Cams ho familiaris similar to OWU moloα.
Cfa.7675,1 domain-containing XM 5341 DNAJC1 subfamily C,
,A1 at 2.63E-03 1.45E-02 0,74 (LOC476930); mRNA 31 member 15
PREDICTED: Canis DnaJ (HSP40) ftimiliaris sitnilar to Cms] (Hsp40) homolog, homolog .
Cfa.16320. sυbf3mily C; member 3 XM 5341 subfamily C.
1.A1 s at I.96E-03 1.336-02 0.68 (U)C476966); mRMA 66 DNAJC3 member 3
PREDICTED: Cams fβmillarts similar to DnaJ DnaJ (Hso40) (Hsp40) homotog; homolofl, subfamiiy C; member 7;
Cfa.7924.1 transcnpt variant 2 XM 5376 subfamily C,
.A1 s at 7,tlE-02 6.34E-O2 0.76 (LOC480519); mRNA 39 DNAJC7 member 7 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000135_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000136_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
faniiiiaris similar to embryonic ectoderm development; trarwcrφt embryonic
Cfa.10198, variant 4 (LOC476779); XM 8525 ectoderm
1.A1 s at 2.2SE-03 1.37E-02 0.76 mRNA 71 EED development eukarvotic translation elongation
PREDICTED: Cams factor 1 delta famlllarls similar to (guanine
CfaAffx.28 eukaryotic translation nucl elongation factor I delta; eotide 66.1.S1 S transαipt valiant 1 XM 5323 exchange at 3.61E-03 1.60E-02 07S (LOC47S115); mRNA 45 EEF1D protein)
PREDICTED: Canis fβmiliaris similar to Eukaryoee trβnslatton elongation factor t eukarvotic epsiion-l (Mtiltisynthetase translation complex aw>tliary elongation component pi8)
Cfa.1174S. (Bongatiori factor plS) XM 5358 factor 1
1.A1 s at 2,UE-(M 9.066-03 0.68 (LOC4787I7), rc.RHA 82 εεFiεi epsilon 1
EF-hand
CfiaAfftc.26 I PREDICTED: Canls calciu famιliari5 hypoUieCcal m 979.1.S1 ai LOC480634 XM 5377 binding
L 2.466-03 1.416-02 1.4S (LOC4S0δ34); mRMA 54 SFCABS domain 5
PREDICTED: Canls familiaris similar to Vr EF-hand hand domain family;
Cfa.18530, membet Al XM 5431 domain family,
1.S1 s at ι.iaε-02 2.40E-O2 0.76 {(.0O186044); mRNA 70 EFHA1 member A 1
PREDICTED: Canis familiaris similar to eukaryotic Translation initiation translation factor eIF-2B epsilon initiation factor
CfeAffx,18 I sυbυnit (eIP-28 GDP-GTP 2Br subunit 5 exchaoge factor); L1.S1 al transcript variant 3 XM 8524 epsilon. t 4.84E-03 1.75E-02 0.71i (LOC488103); mRNA 30 EIF2B5 B2kPa
PREOICTED-. Osπls familieris similar to Eukaryotic translation initiation factor 2 suounit eukarvotic 1 (EukaryoPc translation translation Initiation fsctor 2 alpha initiation factor subunit) (eIF-2-alpha)
Cfa.19645, {Elf-2aipha) (EIF-2A) XM 5374 2. subunit 1
1.31 s at 9.66E-04 1.16E-O2 0.72 {LOC4S0361); mRNA aipha, 35kDa
PREDICTED: Cams familisris βirnilsr to Eukaryotic translation Initiation factor 2 sstbunlt eukarvotic 2 {Eukaryotic translation translation inibabon fsctof 2 beta initiation factor subunit) (eIF-2-beta);
Cfa.304.1. transcript variant 7 XM 8583 2, subunit 2 A1 s at 3.3SE-(W 9.06E-03 0.71 (LOC477197); mRNA 44 E1F2S2 beta, 38kDa Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000138_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
faniiiiaris similar to RNA elongation polymerase Ii etongatton factor, RNA factor £{12; transcript
Cfa.15358, variant 1 (LOC4S8899); XM 5460 polymerase i
1.A1 at 7.8SE-04 1.10E-02 0.63 roRNA 16 ELL2
ELOVL family member 5,
Bcs taurυs ELOVL family member 5: elongation of elongation of tong chain fatty acids long chain (røil/Bo2; SUR4/£io3- falty acids like; yeβst); mRNA (cONA (FEN1/EIQ2, done MGC:128086
Cfa-172Q2. tMAGe.7988977); SUR4/EIO3-
LSI at 4.69£-03 1.73E-02 0.7*? complete cds BC105391 ELOVL5 like, yeast)
ELOVL family member S. elongation of long chain fatty acids
CfeAffx,42 Pongo abeiii mRNA; cOHA (FEN1/E1Q2, 90.1.51 s DKFZp469M0522 (from SUR4/EIO3- at S.8SE-02 5.56E-02 Q.7<? done DKFZfW69MOS;22) CR857140 EL0VL5 like, yeast) elongation
PREDICTED: Cams protein 2 farroliaris similar to
Cfa.10482. etoπgator protein 2. XM 5372 homolog (S.
1.A1 at 3.SSC-03 1.56E-02 0,75 (LOC4801 SS); mRNA 81 ELP2 cerevisiae) familiaris similβr to EMG1 Probable πbcsome nucleolar
CfaAf{χ.22 biogenesis protein NEPt prot (C2f protein); t'ar«cript ein 271.1.81 s variant 2 (LOC47770S); XM 8482 homolop (S. at 8.636-04 X.13E-O2 0.7 mRNA 80 EMG1 cerevisiae)
PREDICTED; Canls ectonucleotide familiaris similar to pyrophosphat ectonwcteotidε ase/phosphodi pyrophosphatase/phoϊph ocJlesteiase S {putative esterase 5
CfaAffx.39 function) (LOC481S24); XM 5389 (putative 48. LSi at -.606-02 2,etE-O2 0,77 mRNA 45 ENPPS function) predicted
CfaAffx,31 I PReDICTED: Mus ENSMU muscuius sirniiβr to gene, 149.1.S1 ai nudear transport factor 2 XM 0014 SGOOOO ENSMUSGOO t 3.6S6-04 9.61 E-03 0.73 (LOC1000434«2), mRNA 80585 0071497 000071497 familiaris similar to Memmalian ependymln rotated pfotetn-1 ependv precursor (MERP-I) min
Cfa.4059.1 (UCCl protein) XM 8466 related protein ,A1 at 9.53E-02 7.38E-O2 IAZ (LOC6OM03); mRNA 51 EPDR 1 1 (zebrafish) famlllarts similar to glutamyt-prolyi tRNA gluta svnthetase; transcript myl-prolyl
Cfe,222.1. vsiiatΛ 2 (LOC47896.); XM 8443 tRNA S1 s at i.77E-(M 9.00E-03 0.72 mRNA 75 EPRS synthetase Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000140_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000141_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000142_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PRK)ICTgD: Cβnls F-box and familisris similar to F-ϋox and ieucirte-ticfi repeat leucine-ricrt
Cfa.18553, protein 5 isoform 1 XM 5362 repeat protein
LSI s at 4.13E-03 1.67E-02 0.7S|(LOC479085); mRNA 32 FBXL5 5
PREDICTED. Cams F-box and
CfaAffx.23 famlllarls similar to F-oox l ich and leuone-fich repeat eucine-r 557.1. S1 s protein 5 isofcrm 1 XM 5362 repeat protein at ?..40€-03 1.40E-02 0,75 (LOC47903S), mRNA FBXL5
CfeAfOδ PREDICTED: tans 22. familiaris sirrsilar to F-srax 379,1, S1 ai onty protein 2 XM 5354 F-box protein t i 5.596-02 5.42E-O2 1Λ (LOC47S231); mRNA 06 FBXO2
PREDICTED: Cams familiaris similar to F-srax
Cfa.5036.1 onty protein 22 isoform a XM 5447 F-box protein
,A1 s at 2.32E-04 9.06E-03 0.75 ((.00487672}; mRNA 96 F8XO22 22
PREDICTED: Pan troglodytes hypothetical
Cfa.19659, protein LOC73S7S2 XM 001 1 F-box protein
..69C-02 2.916-02 1S (LOC73S792); mftNA 35277 FBXO28 28
PREDICTED: OmIs familiaris similar to F-Ssox αa.19071. onty protein 4 isoform 1 XM 5463 F-box protein
LSI s at 2.23E-02 3.31E-02 0.76 (LOC4δ9220); mRNA 38 F8XO4 4
Fc fragment of
IQG, high
PREDICTED: Canls familisris nigti affinity IgG affinity Ia.
Cfe.173.1, Fc gamma receptor i XM S504 receptor A1 s at 5U8E-O3 2.226-02 0.77 (FCGAMMASJ); mRNA 58 (CD64) fem-1
Cfat.2673.1 Homo sapiens KIAA0396 homoloq b (C, ,A1 at S.7Sε-04 1.03E-02 0,7^r«RNA; partial cds AB007856 FEM1B eiegans^ familiaπs similar to flap flap structure- sbucture-specific sp enctonuclease i; ecific
Cfa-1780.1 transcript variant 1 XM 5332 endonuclease
,S1 at 6.67E-03 1.9S6-02 0.73 (LQC476GS3); mRMA 71 FEN1 1 familiaris similar to fasciculation fβscieuiatton and and ejofigaboπ protein z«ta 2 (2yqiπ I!); transcript elongation
Cfe,7269,1 vsiiatΛ 3 (LOC463Q31); XM 8580 protein zeta 2
,A1 a at Ϊ.71E-02 3.6SE-02 0.77 mRNA 68 FEZ2 feyqin iP familiaris similar to Pumarate hyritatase; mitochondrial precursor (Fumarase}; transcript
Cfeι.1169B. variant 3 (IOC480092): XM 8579 fumarate
1.A1 S at 3.S3E-03 1.59E-02 0,75 mRNA 11 FH hvdratase famiiieris similar to Fumarate hycrstase;
CfaAffx.24 I mitoctiondrial precursor (Rjmarase); transciipt 074.1, S1 al variant 3 (LOC480092); XM 8579 fumarate t 2.686-04 9.UE-O3 0.72 mWA 11 FH hvdratase Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000144_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
fiermllarts similar to Far upstream element binding far upstream protein 1 (FUS6 binding element
CfaAfftc.31 ! protein 1) (FBP) (DNA (FUSE) heficase V) (HDH V); 174.1.S1 ai tf adscript variant 20 XM 8627 binding I I 3.72E-02 4.336-02 6 (LOC490201); mRNA 53 FUBP1 protein 1
PREDICTED: Cams fragile X famϋiaris similar to fragile mental X m«nt<*l retardatioπ- related protein 1 isofcrm retardation,
Cfe.19777. b; transcript vsnβnt 12 XM 8513 autosomal 1.S1 s at 169E-03 1.29E-02 0.72 (LOC478642), mRMA 95 FXR1 homoloα 1
PREDICTCD: Cams ferroliaris similar to Ras- GTPase-actsvatmg protein GTPase binding protein 1 (GA? activating SH3-do»_5in binding protein (SH3
CfaAfftc.27 pixjteln 1) (G3BP-1) (DNA do helicase vm) (HDH-VSII); main)., 301.1.31 s transcript variant Z XM 8622
1.36E-04 3.90E-03 0.76 (LOC479322); mRMA 69 G3BP1 protein 1
PREDICTED: Cams GTPase familian'5 similar to R«s- activating GTPsse activating protein protein (SH3
CfaAf&(,13 SM3 domaii\-blndi!>9 do protein 2 isoform a; main) 299.1.81 s transσipt vsrisnt 7 XM 8510 binding
4.61E-03 1.72E-02 0.77 (LOC478429); mRNA 19 protein 2
UDP-N-acetvi- alpha-D- galactosamine
PREDICTED. Cams : polypeptide N famlllaris similar tø acetylqalactos potypeptlde N- a scetytgalBctosaminydrans* minyltransfer
Cia.20087. erase 2; transcript variant XM 5359 asc 3 (GaINAc
1.31 s at 2.076-02 3.19E-O2 0.76 i (LOC478774): mRNA 40 GALNT3 J31
UDP-N-acetyl- alpha-D- galactosamine
PREDICTED. Cams : polypeptide N famillaris similar to acetylαalactos
CfaAffx,17 i potypeptlde N- aminyltransfer scetytgalBctosaminyitrans* 476.1.S1 ai erase 3; transcript variant XM 8536 ase 3 (GaINAc t 3.84E-02 4,4tE»02 0.73 2 (LOC478774): mRNA 27 GALNT3 J3i
PREDlCTED: Canls GTPase familiaris similar to activating
CfeAffx.30 I GTPase activating piuteln prot and VPS9 domains 1; ein and 916.1 -S1 al trariKfSpt variant 3 XM 8581 GAPVD VPS9 t 7.426-03 2.02E-O2 0.68 (IOC48072S); mRNA 42 1 domains 1
PREDiαED: CaniS famtliaris similar to Olycyl1 tβNA synthase (Giyctne-
Cfe.3929.1 «NA ligase) (GIyRS) XM 5325 olvcyl-tRNA
,A1 a at 9.8SE-M l,l6£-02 0.74 (UX47526S); rr.KHA 02 GARS synthetase Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000146_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000147_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
guanine nucleotide
PREDICTED: Cams protein (G familiaris similar to protein), alpha Guanine nucleotide- inhibiting binding piotein G(k);
Cfa.19946. alpha subuntt (G(:) alpha- XM 8495 activity
1.S1 s at I.63E-03 1.286-02 0.71; 3) (LOC611S10); mRNA 21 GNA13 polypeptide s guanine nucleotide binding
PREDICTED: Canis protein (G familiaris similar to protein), alpha
CfaAffx.30 I Guanine nucteotide- birx&ng protein G{k): inhibiting 335.1.S1 ai alpha subunit (G(i) alpha- XM 8495 activity t l,16E-02 i.'Wε-oz 0.77 3) <lOC6n8.0); mRNA 21 GNAI3 polypeptide 3
PREDICTED: Cams glucosamine- families aimilsi to glucosamine-ptiosphftte N phosphate N-
Cfa.1666.1 scetyltransferase l XM 5374 GNPNA acetyitransfer
.S1 at 2.86E-02 3.75E-02 OJ^ {10O18Q32S); mRNA 48 T1 ase 1 famiiisris similar to Goigi autoaπtigen; ςolgin subftimliy A member 5 oolαi αaAffx,17 i (Golgin-84) (RET-fused autoantig gene S protein) (ReMi en, 247.1.S1 ai protein) (LOC4δ0233); XM 5373 GOLGA golgin t i.ssε-03 l,26E»02 075 mRNA 56 5 subfamily a, 5
PREDICTED: Canls famiiisiis similar to Qo'gt golgi phosphopixrtein 3 (Coat- protein GPP34) (Trans- phosphoprotei
Cfa.1625.1 Goigi protein GMκ33) XM 5463 n 3 (coat-
-A1 at i.isε-02 2.4JE-02 0.74 (LOC4S92Λ1); mRNA protein)
PREDiαED: Canis golgi SNAP αaAfix.29 I farmliaris similar to gotgi SNAP receptor complex receptor 053.1.S1 ai nvernber 1 tsofoiw 2 XM 5483 complex t 3.11E-02 3.93E-02 0.72 ILOC49U85); mRMA 05 GOSR1 member 1
PREDICTED: Cams golfli SNAP
CfaAffx,29 familiaris similar to golgi r SNAP receptor compSex eceptor 053.1. Si s member 1 sσform 2 XM 5483 complex at 4.90E-04 1.00E-02 0.73 (LOC49S185); mRNA 05 GOSRI member 1 glycerol- 3-
PRSDICTED: Macaca phosphate mulatta oJyceiol-3- dehydrogenas phosphate dehydrogenase 2 el
Cfa.761.1, (mitochondrial); transcript XM 0010 (mitochondrial A1 at 9.14C-03 2.22E-O2 O.Hvarant 1 (GP02); mRNA 86842 GPD2 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Caws famiHaiis similar to putative NFkB activating G prot protein 373 isofortn 1: ein-
Cfa.12478. transcnpt variant 3 XM 8628 coupled
1.S1 at 3.10E-03 1.S3E-O2 0.65 (LOC6U<*91); mRNA 72 GPR177 receptor 177
CfeAffx.26 I PREDICTED: Cams G prot farmliaris similar to G ein- 530.1. S1 ai protein-coupled receptor XM 5479 coupled t i.srøe-02 3.14E-02 0,73 65 (LOC490821): tnWlA 43 GPR65 receptor 65 qlutamate receptor,
Mus musculus giutamate ionotropic. receptor; tonotropK;
Cfa.3254,1 NMDA2Θ (epsiloπ 2) NM 0081 NMDA28
■S1 at 5.15€-04 1.01E-02 1.38 (GrirUb); mRNA 71 Grin2b (epsilon 2)
PREDICTED: Cams G-iich RNA famillarts similar to G-rlch sequence RNA sequence btndins
Cfa.1176.1 factor 1 (LOC475170); XM 5324 binding factor
JH5JL 7.40E-03 2,O2E»O2 0.7S mSNA 02 GRSFI 1
PREDICTED: Cams famillaris similar to Gl to S phase transition pretein 1 homolog (GTP-binriliig protein GSTl -HS);
Cfa.20162. transcript variant 2 XM 8582 G1 to S phase
1.S1 s at 4,43E-(M 9.786-03 0.76 (LQC479846); mRMA 62 GSPT1 transition 1
PREDICTED: Canls famiiiaris similar to peptide chain release
Cfa.S851,1 facto,' 3; transcript variant XM 5380 G1 to S phase
Al a at Ϊ.01E-02 2.31E-O2 0.77J1 (LOC4S0921); mRNA 42 GSPT2 transition 2 fβmillarts similar to
CfaAffx,16 glirtattwne-S-transfetβse glutathion ome^a 1; transcript e S- 567.1. S1 s variant 1 (LOC477813); XM 5350 transferase at 2.2SE-03 1J8E-02 0.72 mRNA 07 GSTOI omega 1
PREDICTED: Canis general famiiiaris similar to transcription
CfaAffet.10 Transcription initiation factor IE. factor HE beta suburot ■■ 1.31 s (TFHE-b«a) XM 5326 polypeptide 2, at 2.59E-03 1.S16-02 0.76 (LOC47SS97); mRMA 14 GTF2E2 beta 34kDa general transcription
PftEDICTED: Cams factor DiC, fβmillarts hypotheticβl
CfaAffx.βB -OC481961 XM 5390 polypeptide 6. 06. LSI at 2.806-04 9.HE-O3 0.72 (LOC481961); mRNA 82 GTF3C6 alpha 3SkDa Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000150_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000151_0001
ISO Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000152_0001
ISl Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000153_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000154_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000155_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
CfaAffet.14 Homo sapiens mRNA; int cDNA DKF_p636P062.5 egrator 816.1.S1 s (from done complex at 2.59E-02 3.S6E-02 0.75 DKFZp6S6PO6215) BX538203 INTS8 subunit 8 irort- responsive
PREDICTED: Equus caoallus Iron-responsive element
Cfa.16494. element binding protein 2 XM 0014 1.81 at i.5ie-03 1.25E-O2 0,73 (!RE82); mRNA 88966 IRE82 protein 2
Bos taurus isochorssmatase domain
CfaAfix.20 containing I; mRNA isochoris (cONA done MGC: 14SS32 mata
07.1.81 s IMAG6-8271SS2), se domain at 3.2S€-02 4.02E-O2 0.7S complete cds BC148130 ISOC1 containing 1
inteαrin, alpha
PREDICTED: Cams 4 (antigen famillaris similar to CD49D, alpha
CfaAffx,21 I lntegrm alpna-4 precursor 4 subunit of (lntegrtn aipha-IV) (VLA- 882.1.S1 ai 4) (CCMSd) (LOC488429); XM 5455 VLA-4 t 1.87E-03 1.32E-O2 0.73 mBNA 51 ITGA4 receptor) famtliaris similar to Integrin beta-1 binding protein 1 (Integrin
CfiaAfftc.59 cytopfssmic domam- int «$5oci«ted protein i) eαrin beta 1 87.1.S1 s (ICAP-I) (LOC475660), XM 5328 binding at ..24E-03 1.236-02 0.7 mRNA 68 protein 1
FRcDICTEUrCaniS iagunal ftimiliaris sitnilar to
Cfe.6183.1 jagunai homoiog 1 XM 5417 hornoloq 1 .Ai at 1.906-02 3.076-02 1.43 (LOC484661), mRNA 76 JAGN 1 (Drosophila) faniiliarts similar to
CfiaAflx.12 jumon): domairi iu containing IA: transcript monii
161.1.S1 S variant 1 (L0O7S763); XM 5329 domain at 4.34E-03 1.69E-02 0.7^ mRNA 73 JMJPIA containing 1A familiaris similar tø phosprtaadyiserme receptor, transcπpt
Cfa.17114. variant 2 (LOC48333S): XM 8439
1,81 at 1.23E-02 2,StE»O2 0.74 mRNA 87 JMJD6 containing 6
PRSDICTED: Pan kelch repeat ttαglodytes WId! iβpeat and BTB and ST8 (POZ) domain
Cfa.511.1. containing 7 (KBTBD7): XM 5226 (POZ) domain S1 at U76-02 2.54E-O2 0.76 mRNA 66 KBTBD7 containing 7
PREDICTED. Cams KH domain famillarts similar to K.H containing. domain containing; RNA RNA binding,
CfaAlix.16 I binding; signal signal transduction associated i; 854.1.S1 ai transcript variant 1 XM 5444 KHDRB transduction t I.87E-04 9.00E-03 0.65 (LOC487316); mRNA 42 S1 associated 1 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000157_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000158_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
La. ribonucleopfot
PReDICTED: Bos taυrus ein domain
Cfa.14608. similar to Ia (dated XM 5820 family,
1.A1 at i.soe-02 2.7SE-02 0.69 protein (LARPl); mRNA 17 LARP1 member 1
PREDICTED: Canis familiaris similar to Neutrophil geiatinase- associate<l lipocalin precursor (NGAl) (P_5) (25 kDβ alpha-2- mlcrogtobuliivreiated
CfaAfix.30 I subunit of MKP-9} (Upαcaϋn 2) (Oncogene 748.1.S1 al 24p3): transcript variant 2 XM 8572 t 6.69E-02 6.00E-02 072 (LOC491320); mRNA 29 LCN2 lipocalin 2
PftEDICTΪD: Cams lymphocyte fβmillarts similar to cvtosolic Lymphocyte cytosolic prot protein 2 (SH2 domain- ein 2 (SH2 containing leucocyte protein of 76 køa) (SLP- conlaininα 76 tyroairse l phosphoprotein) (SLP76): eukocyte
Cfa.21232, ttartscript variant I XM 5462 protein of
1.S1 s at 4.39E-03 1.6SE-02 0.73 (LOC4S9126); mRNA 44 LCP2 76kDa)
Leo1 ,
Paf1/RNA
PR6DICTED-. Canis polymerase familieris similar to complex senescence co dowrsrsgulated leot-li«s; mponent,
Cfa.9446.1 transαipt variant 4 XM 8580 homolop (S,
,A1 s at 3.47E-03 1.S8E-02 0.7S (LOC47S310); mRNA 08 LEOI cerevisiae) fβmlilarts similar tø LFTKl domain containing 1 soform 1; transcript
Cia.10550. variant t (LOC607861): XM 8451 2.S1 at i.886-04 9.00E-O3 0.64 mRNA 92 LETMD 1 containing 1 lectin,
PREDICTED: Canis familiaris similar to flalactoside-
Cfet.11075. galectm S lsoform 3 XM 5363 binding, 2.A1 s at I.69E-03 1.29E-02 0.6S (I.OC479193); mRMA 35 LGALSS soluble. 8
FKEUICTtϋTCaniS leuciπe-rich ramϋiaris sirr^tar to Leucine -rich repeat- reoeat- containing G-pfotein conlaining G coυpled receptor 4 prot precursor (G-p-Otein ein-
Cfa.14080, coupled receptor 4S) XM 5340 coupled 1.A1 at 6,99£-04 1.08E-02 1.32 (LOC476896); mRNA 98 LGR4 receptor 4 farmllaris similar to Itgatin,
Cfa.2087,1 transcript variant 1 XM 5361 .A1 at 2.86E-03 1,4SE»O2 0.6li (LOC478951); mRNA 09 LGTN ligatin Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000160_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
CfaAffet.22 I PREDICTED: Equus hypothetical cattallus hypothetical 91S.1.S1 ai LOC100051235 XM 0014 LOC 100 IOC10005123 t 2,49E-02 3.S0E-O2 0.74 (UX1OOO51235); mRNA 89111 051235
PREDICTED: Equus similar to cabaiius similar to arqintn nd arglnin« and giutamate e a
Cfa.16441. rich 1 (LOC10005J338); XM 0014 LOC100 αlutamate rich
I.43E-04 8.S06-03 0.6S mRNA similar to
PREDICTED: equus protein caballus Similar to protein phosphatase 1; tegulβtory phosphatase
Cfø.14225. subunft 15A XM 0014 LOC 100 1 , regulatory
1.A1 s at 6.72E-02 6.O2E-O2 0.76 (LQC100051332); mRNA 89532 051382 subunit 15A similar to proteasome
PREDICTED: Equus (prospme,. cabaiius similar to maαopain) proteasome (prosortw; 26S subunit, iDscropain) 26S subunit;
Cfa.10188. non-ATPβse; 14 XM 0014 LOC100 non-ATPase,
1.S1 at 9.S7E-CH l.tSE-02 0.74 (LOC100051409); mRMA 93620 051409 14 similar to 1- phosphatidylin ositol-4.5- bisphosphate phosphodieste rase beta 1
PREDICTED: Equus (Phosphoiπosi cabaiius similar to 1- tide phosphaadyϋπosJtol -A; 5- phosphoiipase btsφhosphat« phosphodiesterase beta- 1 CJ. (Phosprtoirsositlde (Phospholipas prtosphollpase C) e C-beta-1 ) tPnospholipa5« C-beta-1) (PLC-b (PLC-bets-1) (PLC-I) (PLC eta-1) αa.10853. 154) (LOCtOOOSlSSS); XM 0014 LOC100 (PLC-I) (PLC-
1.A1 at ..62E-02 2.8SE-02 mftNA 93603 051558 154) similar to
Ubiquitin carboxyl- terminal
PREDICTED: Equus cabalfus simitar to hydrolase UbiquiHn carboxyt- isozyme L3 terminal hydrolase (UCH-L3) isozyme L3 (0CH-L3) (Ubiqultin thioesterass (Ubiquitin
Cfa.16981. 13) (LOC1000S2000); XM 0014 LOC 100 thioesterase
1.S1 s at 6.31E-0S 8.40E-03 0.71! mRNA 88246 052000 L3) similar to SON
PREDICTED: Equus DNA binding
CfaAffx,17 cabslius similar to SON prot DMA binding protein; ein. 03,1 -S1 S tsatorm f (predicted) XM 0019 LOCIOO isoforro f at 7,S«E"02 6.42E-02 0.73 (LOC1000S2256); mRNA 15560 052256 (predicted) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000162_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000163_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Equus cattallus simHar to
Cfa,5595,1 cofβctor A XM 0015 LOC 100 similar to
.A1 at 3.46C-03 1.S8E-02 0.76 (.OC100065465); mRNA 04660 065465 cofactor A
Cfa.2674.1 cabβllus similar to rabi 2 XM 0014 LOC100 similar to ,S1 at 5.S2E-CH 1.O2E-O2 074 (LOC100066US); mRMA 96510 066116 rab11
PREDICTED-. Equus hypothetical cacallus similar to spildng factor YTS21-B; transcript protein
Cfa.18972. variant 2 XM 0015 LOC100 LOC10006630
1.S1 s at 3.646-03 2.27E-02 f (LOC100066303); mRNA 01526 066303
PREDICTCD: Equus cabalius similar to N- 8cetytgalBctosarn:ny)trans< erase 7 (Protein-UDP acetylgalactosaminyltsansf erase 7) (UDP- GaINAe: pofypeptida N- «scetyk)alactosarniπyitfaπs( erase 7) (Polypeptide GaINAc transferase 7) (GalNAe-T7) (pp-GaNTsse hypothetical
Oa.19409. 7) (LOC100066545); XM 0019 LOC100 LOC 100066541
1,81 at 4.Q7E-05 7,SSE»O3 0.7 mRNA 15557 066545
PREDICTED: Equus similar to cabalfus simitar to prot Proteasome subunlt bete easome
Cfa.β274.1 type-7 (LOC100067317); XM 0015 LOC100 beta 7 subunit
.S1 s at 1.026-04 8.9OE-O3 0.73 mRNA 02120 067317 proprotein similar to B-
PREDICTED: Equus cell scaffold
CfeAffx,16 I caballus similar to 6-cel! prot scaffold protein with ein with H. S1 al ankyiϊn fβpe»ts XM 0014 LOC100 ankyrin t 2.89E-03 1.49E-02 0.6^(LOC1000S7773); mftNA 97747 067773 repeats 1
PREDICTED: Equυs cacaltus similar to Acyi earner protein; similar to Acyl mitochondrial precursor carrier protein, (ACP) (NADH-ubiςuinone Mitochondrial oxidoredwctase 9.6 kDa
Cfa.10920. -ubursit) (α-SDAP) XM 0014 LOC100 (ACP)
LSI x at 1.776-04 9.0OE-O3 0.6S (LOC100069079); mRNA 98903 069079 (5partial) similar to
PREDICTED: Equus chromosome cabslius similar to 6 op chromosome 6 open en
CfaAfix.43 reading fiame 142 XM 0014 LOCIOO reading frame 35. LSi at 4.seε-o4 9,87E-OJ 1.34 (LOC10006SS7t); mRNA 99311 069574 142 similar to
PREDICTED: Equus chromosome
CfaAffx.43 caballus similar to op chromosome 6 open en 35.1.S1 x reading frame 142 XM 0014 LOC 100 reading frame at 3.2SE-04 9.28E-03 1.32 (LOC10006S574); mRNA 99311 069574 142 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Equαs cabalius similar to Veacfe transport protein USEl (USεi-IIke protein) hypothetical
CfaAffr,23 I (Putative MAPK -activating protein protein PM26) (Protein 811.1.S1 al p31) (UOCI00070008); XM 0015 LOC100 LOC 10007000 t i 3.60E-03 1.60E-02 0.71 mRNA 03032 070008 8 hypothetical
CfaAfix.16 PREDICTED: Equus prot cabaiius similar to zinc ein 114.1.S1 S finger protein 362 XM 0014 LOC 100 LOC10007002 at I.30E-02 2.S7E-02 .33 (.OC100070027}; mRNA 99712 070027 similar to synaptotaqmin binding,
PREDICTED: equus cytoplasmic cabaiius similar to RNA SVNCRIP protein,
Cfe.2265.1 transαipt variant 2 XM 0019 LOCIOO interacting
.Ai at I..1E-02 2.-WE-O2 0.75 (LOC100070472); mWIA 15136 070472 protein
PREDICTED. Equus similar to cabaiius similar to spiking splicing factor, factor; arginlne/seriπe*
Cfia.277.1, rich 6 (LOC100070669); XM 0015 LOC 100 aiQinine/serin S1 at 2.38C-03 1.40E-02 0,75 mRNA 00335 070669 e-iich 6
PREDICTCD: equus cabaiius simitar to
CfaAffic.11 I eukaryotic transJatiαo initiation factor 3; sυbunit 227.1.S1 ai 5 epsiton; 47VDa XM 0015 LOC 100 similar to t ! 3.99E-02 4.S0E-02 0.75 (.OC100070877); mRMA 00555 070877 hCG 1784554
CfaAffr.26 I PREDICTED: Equus si cabβllus similar to RA051 milar to 862.1.S1 ai rtonvolog C XM 0015 LOC 100 RAD51 t ! i.ase-03 1.23E-O2 0.73 (UX100070366}; mRNA 00643 070966 homolog C
PREDICTED: Equus similar to cabaiius similar to SEC63 TYarøiocatsoFi protein
Cfa.2073.1 SEC63 homofog XM 0015 LOC100 homolog (S,
.81 at 7.72E-03 2.06E-02 0.71! (LOC1000720θ6); mRNA 01960 072096 cerevisiae) similar to Protein disulfide- isomerase A6 precursor (Protein
PREDICTED: Equus cabslius similar to Protein disulfide dlsulfide-Bomerase AS isomerase P5) precursor (Proteirs (Thioredoxin dlsulfkJe i&onκra&e PS) domain- (Thioredoxin domain-
CfaABx.61 containing protein 7} XM 0015 LOC 100 containing 63.1.51 at 4.69e-03 1.73E-02 0,62 (LOC1OOO72358); mRNA 02274 072358 protein 7) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Equus hypothetical cattallus hypothetical
CfaAfjx,94 LOC100072521 XM 0015 LOC 100 IOC10007252 96.1.51 at 2.81E-02 3.73E-O2 0.72 (.OC100072521); mRNA 02483 072521 1 similar to
PREDICTED'. Equus protein cabβllus similar to protein phosphatas phosphatase 2; catalytic e
Cfa.1403,1 suburat; aipha XM 0019 LOC100 2, catalytic .S2 s at 3.09C-04 9.27E-03 6 (LOC100072780); mRNA 17927 072780 subunit. alpha similar to
PREOlCTED. Equus protein cabalfus simitar to protein phosphatas phosphatase 2; catalytic e
CfaAffx.23 subunit; a!pκa XM 0019 LOC100 2. catalytic
93.1.S1 at 4.53E-03 1.71 £-02 0.76 (IOC100072780); mRNA 17927 072780 subunit. alpha
Xertopus trøplcslts hypothetical protein hypothetical IOC1CXH3S097; mSN4 prot (CDNA done MGC; 172.910 ein
Cfa.5559,1 IMAG6:7694930); LOC100 LOC10013509I .A1 a at S.2SE-03 2Λ2E-O2 1.3f complete CdS BC 155703 135097 similar to Ubiαuitin- coniugatinp enzyme E2 Z (Ubiquitin- protein lioase
PREDICTED: Bos taums Z) (Ubiαuitin similar to UWquftin- conjugating enzyme E2 Z carrier protein (Ubiquitin-proteiπ ligase Zϊ (Uba6- Z) (UbiqurUn earner specific £2
CfaAffx.25 i protein 2) (Uba6-spec)f!c conjuQatinq £2 corrjugatlng en-v^e i) 830.1. S1 ai (Usel) (LOC100i381?8); XM 0017 LOC 100 enzyme 1 ) t 2.S6E-03 l,44E»02 0.76 mRNA 89275 138178
PREDICTED-. Eqtlus similar to HLA- cβbBllus similar to HLA-S
Cfa.10131. associated transcript 1 XM 0019 LOC 100 B associated
1.S1 s at 1.10E-02 2.38E-02 1.31; {LOC10014C384}; mRNA 17617 146384 transcript 1 similar to zinc
PREDICTED: Sus scrota finger and similar to zinc finger βnci
Cfa,1992,1 8T8 domain containing 1 XM 0019 LOC100 BTS domain
,S1 at 8.07E-03 2,tOE»O2 0.72 (LOClOOl 52273}; mRNA 25789 152273 containing 1 similar to
PREDICTED: Sus sαofa polyqluta similar to polyglutamiπe- mine-
Cfa.3312,1 contaimng proteirs XM 0019 LOC 100 containing
4.95E-02 S.07E-02 0.71! (LOC1001S276δ): mRNA
CfaAfftt,26 I
PREDICTED: Sus scrofs 442.1.Si έ simiiar to TIPIN protein XM 0019 LOC100 similar to
L I.23E-03 1.23E-O2 0.72 (LOC1001S3268): mRNA 25231 153268 TIPIN protein Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to Presquaiene diphosphate phosphatase
(Phosphatide acid phosphatase
PREDICTED: Sus scrota typβ .2.cjomajn: similar to Prestiualeoe diphosphate phosphatase containing {Phosphatide ackt protein 2) phosphatase type 2 (PPAP2 domain-containing protein domain- 2) (PPAP2 demain-
Cfa.8329.1 cotitaltiing pitΛ-rln 7.) XM 0019 LOC100 containing
.A1 at 4.64€-03 1.73E-O2 0.75 (LOC1001S3280); mRNA 26782 153280 protein 2) similar to DNA damaαe- inducibie transcript 4 protein (Protein regulated in development
PREDICTCD: SUS scrofa and DNA similar to DNA-<iamage- damage irtducibie transcript 4 protein (Protein regulated response 1) in development aπo DNA (REDD-D damage response 1) (H1F-1 CR£OD-i) (HJM r responsive protein esponsive
Cfa.8215.1 RTPSOl) XM 0019 LOC1Q0 protein .A1 at i.oτε-03 1.20E-02 0.7 (LOC100153S-1); mftNA 25275 153821 RTP801]
PR6D1CTED-. Sus scrofa similar to ceil division si cycle associated 7; milar to cell
Cfa-12793. tf adscript variant ϊ XM 0019 LOC100 division cycle 1.A1 at 9.32E-03 2.236-02 0.73 (LOC100154583): mRNA 28628 154583 associated 7 similar to
PREMCTED: Sus scfofø nuclear simiiar to nυciear undecaprenyl undecaptenyi pyrophosphate synthase 1 pyrophosphat
Cfa.9507,1 homotog XM 0019 LOC 100 e synthase 1
■A1 at i.θsε-02 3.04E-02 0.74 (LOClOOl S46S8); mRNA 28072 154658 homoloq similar to Plastin-2 (L-
PREDICTED: Sus scrota plastin) similar to Plastin-2 (L- (Lymphocyte plastin) (Lymphocyte cvtosolic cytosolic protein l) (ICP- 1) (LCS4P); transαipt protein 1)
Cfa.19021. variant 2 XM 0019 LOC 100 (LCP-D
2.S1 a at 3.91E-02 4.4SE-02 076 (LOαOOl 56254}; mRNA 29145 156254 (LC64PΪ Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to vesicle
PRtUICTtD: Sus ϋtrofa trafficking similar to vestcte
Cfa.1028.1 trafficking protein sec22b XM 0019 LOC 100 protein
-A1 at 3.saε-(M 9.S0E-O3 0.65 (LOC100157002); mRNA 28686 157002 sec22b similar to Phosphatidyl^ ositol transfer protein beta isoform fPtdlns transfer
Sus scroti mRNA; protein b done.AMP010019£02: eta)
Cfa.11703. expressed In alveolar LOC 100 (RdlnsTP) (Pi
1.A1 at 6,63E-M 1.06E-02 0.74 macrophage AK230638 157274 TP-beta) similar to ATPase
PREDICTED: Sus scrofa family, AAA similar to ATPase farreiy;
CiB.9211.1 AAA domain containing i XM 0019 LOC 100 .A1 at 4.63E-03 1.72E-02 0.75 (LOC100157471), mftNA 27977 157471 containing 1 similar to
PREDICTED: Sus scfofø FGFRl similar to FGFRl
Cfa.17118. oncogene partner 2 XM 0019 LOC100 oncogene
4.47E-03 1.706-02 0.73 (LOC1001S74θO): mftNA 24597 partner 2 similar to
PREDICTED: Sus scfofø amine oxidase simiiar to amine oxidase (flavin (flavin containing) domain
Cfa.S6S.1. 1 (IOC10015SW7); XM 0019 LOC100 containing) S1 at 2.0βε-02 3.21E-O2 0.74 mRNA 27844 158047 domain 1
PREDICTED, Rsttus norveglcus hypotf>etκal
CfaAffx,14 LOC363725 XR 00822 LOC363 hypothetical 32.1.S1 at 6.17E-04 1.05E-O2 1.31: (LOC36372S); mRNA 725 IOC363725 hypothetical proteifi hypothetical αaAffx.25 LOC3B9203; mRNA ff (cONA clofie ene 106.1.S1 S IMAGE.4S2U85); partial LOC389 suppoited by at S.17E-03 2,t1E»O2 0.76 CSiS BC032431 203 SC032431 pREDiαeo: Pen si troglodytes similar to OTU milar to OTU
Cfa.1161.1 domain containing 6β XR 02312 LOC464
,S1 at S.40E-02 S,32E»02 0.76 (LOC464232); mRNA 282 containing 68
PREDICTED: Pan
CfaAffx,12 ! troglodytes hypothetical LOC467645; transcnpt 773.1.Si ai variant 6 (LOC467645); XM 001 1 LOC467 hypothetical t i 2.77E-0S 7.SS6-03 0.67 mRNA 65269 645 LOC467645
PREDICTEDT P3n similar to troglodytes similar to
Cfe.2514,1 Prenyicysteine oxidase 1 XR 02293 LOC470 Prenylcvsteine ,S1 at 1.90E-03 132E-02 0.74 (LOC470393); mRNA 398 oxidase 1 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000169_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to DnaJ homoioq subfamily A member 1
PReDlCTED- Osπls (Heat shock ramiliβris similar to Dn&3 homolog subfamily A 40 kDa protein member 1 {Heat shock 40 4) (DnaJ kDa protein 4) (OnaJ
CfaAffx.36 protein homoiog 2) (HSJ- ho 2} (HSW), transcript molog 2) 39.1.S1 s variant 3 (LOC474739): XM 8603 LOC474 (HSJ-2) at 3.426-03 1.S7E-0- 0.66 mRNA 55 739 (HSDJ)
PREDICTED: Canis famtliaris similar to CG12822-PA; Isofbrøn A; similar to
Cfa.11753. transcript variant 1 XM 5320 LOC474 CG12822-PA.
1.A1 s at I.63E-02 2-seε-o∑ 0.7 (UX474773); mRMA 04 773 isoform A
PR6D1CTED-. Canls famiiieris similar to si βllagεn; type XXVH; milar to
Cfa.12434. alpha 1 (UX474811); XM 5320 LOC474 collagen, type
1.A1 at 6.0OE-02 S.64e-02 0.68 mRNA 42 811 XXVH. alpha 1
PREDICTED: Canls similar to familiaris similar to Histon Hstone deacetyiase 2 e
Cfa.2884,1 (HO2) (LOC47S03S); XM 5322 LOC475 deacetylase 2
Λ1 s at ..96E-03 1.33E-O2 071i mRNA 70 035 (HD2) familiarre similar to si Prol«n KiAA0i96; milar to
Cfa.20275. trartsσipt variant 1 XM 5323 LOC475 Protein
LSI at 3.89£-04 9.61E-03 0.7S (LOC47S09S); mRMA 27 095 KIAA0196
CfaAffx.21 i FKcDiCTcijrcanis familiaris HypotftetJeai 467.1.S1 ai LOC47S237 XM 5324 LOC475 hypothetical t 5,IJEMM 1.006-02 .39 (UX475237); mRMA 70 237 LOC47S237
CfaAffx.12 PREDICTEDTXaniS farmliaπs similar to 494.1. S1 s CG9882-PA {LOC47S460>, XM 5326 LOC475 similar to at 3.1.E-03 1,S3E»O2 0.72 mRNA 84 460 CG9882-PA
PREDICTED: Cams familiaris similar to H2A similar to H2A
CfaAffx.56 nistone family; member V histone fa tsoform S; transcript mily, 46.1.S1 s variant I (lOWSSOl): XM 5327 LOC475 member V
M. 1.74€-0i 1.30E-0. 0.7 mRNA isoform 5
PREDICTED: Cams similar to famillaris similar to splicing factor splicing factor 35; It kDa
Cfa,5126,1 subunit (LOC47S682), XM 5328 LOC475 38, 14 kDa
,A1 s at 5.84E-O^ l,03E»02 0.6li mRNA 89 682 subunit
PREDICTED: Canis similar to familiaris similar to spltewg factor 36; 14 kDa splicing factor
CfaAfrx.68 suixm>$ αθC4756S2); XM 5328 LOC475 3B. 14 kDa 65.1.S1 at 6.S9E-0S 8.40E-03 0.71; mRNA 89 682 subunit similar Io
PREDICTED: Cams protein ramtllarts similar to containing protein containing single
Cfe.11769. MORN motif In testis XM 5329 LOC475 single MORN
1.A1 at 1.17E-02 2.44E-02 34 (LOC475733); mRNA 42 733 motif in testis Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000171_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000172_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to Mediator complex subunit 4 (Mediator of RNA polymerase Il
transcription subunit 4) (Vitamin D3 receptor- interacting protein
PREDICTED: Csnls famiiiβris similar to complex 36 Mediator complex subunit kDa 4 (Mediator of RNA component) polymerase 1! transcription sυbunlt 4) (DR1F36) (Vitamin D3 receptor- (Activator- interacting protein recruited comptex 36 IcOa component) (DRIP36) cofactor 36 (Actuator-recruited kDa cofactor 3δ kOa component) component) (ARC36) (ARC36) (TRAPZ1SMCCZPC.
Cfa.10497. subunit.. {IOC4769X7): XM 5341 LOC476 (TRAP/SMCC/i
1.A1 at 4.3Oe-OS 1.68E-O2 0.7«? mSNA 20 917 PC2 subunit,..
PREDICTED: Canis si familiaris sirrntar to U2- milar to U2-
Cfe.15101. associated SR 140 protein XM 5342 LOC477 associated
1.A1 s at a.72E-03 1.46E-02 0.76 (LOC477103); mRNA 97 103 SR 140 protein
PREDICTED: Canis si familiaris sirn'Uir to milar to
Cfa.3236.1 Seiefioptotein T prenn-sor XM 5343 LOC477 Selenoprotein ,S1 at 1.64E-03 1.2SE-02 0.73 aOC477113); mRNA 07 113 T precursor
CfaAffx.13 PREDICTED: Cams si o famtϋarls similar to milar t i.1.81 s Setef opfotein T precursor XM 5343 LOC477 Selenoprotein at 5.816-06 6.6SE-O3 0.72 (LOC477113); mRNA 07 1 13 T precursor
CfeAffx,13 CKtUItItU.' <Λtf!iS familiaris similar to 204.1. S1 S CG6878-?A (LOC477215); XM 5344 LOC477 similar to at I.02E-03 1.17E-02 0.72 mRNA 06 215 CG6878-PA
PREDICTED: Oinis similar to familiaris similar to U11/U12 Ul 1/U12 snSNP 35K
Cfa.11288, teoform s (LOC'iTyiSO); XM 5346 LOC477 snRNP 35K
1.A1 at 6.26E-03 1.90E-02 0,73 mRNA 48 450 isoform a
PR£DICT€D: Cams similar to farmliaris similar to U11/U12 U11/U12 snRNP 35K
Cfe.11288. isβform a (LOC4774S0); XM 5346 LOC477 snRNP 35K
1.A1 S at 3.7SE-0S 7.SSE-O3 0.63 mRNA 48 450 isoform a familiaris hypotnePcal αa.1141.1 LOC477476 XM 5346 LOC477 hypotheticai .S1 at 1.1SE-02 2.43E-02 0.7S|(LOC477476); mRNA 74 476 LOC477476 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000174_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to
Thioredoxin- dependent peroxide reductase. mitochondrial
PREDICTED. Cams precursor. famlllarls similar to (Peroxiredoxin Thioredoxln-dependert 3) (Antioxidant peroxide reductase; mitochondrial precursor protein 1 ) (Peroxiredoxln 3) (AOP-D (Antioxidant protein I) (MER5 protein (AOP-I) (MERS protein hornoloq) homolog) (HSC189) (PKK
Cfa.19049. III); transcript variant 5 XM 5350 LOC477 (HBC189)
LSI at 1.076-02 2.37E-O2 0.69 (IOO177839); mRNA 31 839 (PRX M) similar to
PREDICTED: Cams Mitochondrial familiariδ similar to 28S ribosomal
CfeAffx.12 I Mitochondria! 28S prot ribβsomal μncrteln S22 ein S22 259.1, S1 ai (S22mt) (MRP-S22) XM 5351 LOC477 (S22mθ (MRP^ t s.ioε-04 1.15E-O2 073 (LOC^7792f); mRNA 13 924 S22) similar to ubiquinol-
PREDICTED: Cams cvtochrome c
CfaAffx,14 farmϋarls similar to r ubiquiπot-tytodirome c eductase 881.1.51 S reductase binding protein XM 5351 LOC477 binding at S.72E-CW 1.03E-O2 0.6S (LOC477944); mRNA 32 944 protein
PREDICTED: Canis similar to
CfaAf&{.64 familiaris similar to suppr suppressor of G2 slide of essor of 78. LSI s SKPl (LOC477S51); XM 5351 LOC477 G2 allele of at 1,746-02 2.9SE-02 0.75 mRNA 39 951 SKP 1
PREDICTED: Cams similar to farmliarts similar to phvtanoyl-CoA phyCanoyl-CcA
Cfe.11104. hydroxylase precursot XM 5351 LOC478 hydroxylase
LSI at 9.0SE-02 7.1SE-O2 077 (LOC478000); mRNA 84 000 precursor similar to TGF
PREDICTED: Cams beta-inducible famlllarls similar to TCF beta-inducstøe nuciesr prot protein J (L-name refsled ein 1 (L-
Cfa.11121. LNR42); transcript variant XM 5352 LOC478 name related
1,81 at S.80E-03 1,SSE"O2 075 i (LOC478102); mRNA 77 102 LNR42) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to TGF
PREDICTED: Cams beta-indυcible famillarts similar to TCF beta-inducstøe nuclear prot protein J (L-name related ein 1 (L-
Cfa.11121. LNR42); transcript variant XM 5352 LOC478 name related
3.S1 s at 5.23E-03 1.79E-02 0.65 i (LOC478102); mRNA 77 102 LNR42)
PREDICTED'. Csnls
CfaAffx,24 familiaris similar to H2A si histone family; member milar to H2A 175.1.S1 S 2; transuiμt vacant 1 XM 5353 LOC478 histone famity. at Ϊ.42E-03 1.25E-02 0.6-» (LOC47S215); mRNA 90 215 member Z
PREOlCTED. Cams fβmiliaris similar to RIKEN si cDNA 2θOOO64A13; milar to
Cfa.2680.1 transcript variant J XM 5354 LOC478 RiKEN cDNA
,A1 s at 1.146-03 1.20E-O2 0.73 (LOC4782*»2); mRNA 17 242 2900064 A13 similar to ATP
PREDICTED: Cams famillarts similar to ATP synthase, H+ synthase; H* transporting, transporting; mitochondrial
CfaAffx.24 mitoct)o*)d(ial R) FO complex, complex; subunst ά 638.1.S1 x isoform a (LOC478252); XM 5354 LOC478 subunit d at 7.34E-04 1.08E-02 0.7 mRNA 26 252 isoform a similar to ATP
PREDICTED: Canls familisris sirnilsr to ATP synthase, H+ synthase; H<- transporting. transporfng; mitochondrial
CfaAffr.39 mitochondrial PO FO co complex; subunit d mplex, 82.1.51 x isoform s (IQO»7S2S2); XM 5354 LOC478 subunit d
4.2.E-05 7.55E-O3 0,74 mRNA isoform a similar to
CfaAffr.24 PREDICTED: Canis familiaris similar to ribosomal 384.1. S1 s rtbosomβl protein 124-iιke XM 5354 LOC478 protein L24- at 4.24E-03 1.68E-02 072 (LOC4783I3), mRI^A 88 313 like
KKtUIl-I tU.' WIOiS si femillarts similar to milar to
Cfa.9445.1 caimodulin-like -1 XM 5355 LOC478 calmodnlin- -A1 at 1.19E-02 2.47E-0. 0.69 (LOC4783S1); mRNA like 4
PREDICTED. Cams famillarts histone H2AF;
Cfa.1395.1 transcript variant I XM 5356 LOC478
■S1 s at 1.06E-02 2.36E-0. 0.74 (LOC478Λ93); mRNA 71 493 histone H2AF similar to ubiquitin-
PREDICTED: Osπls familieris similar to coniugatino ubiςuitiri-corijugatiri^ enzyme E2D enzyme EJD i (UBC4/S 3 (UBC4/5 homokxj: y&sst);
Cfa.8589,2 transcript variant 3 XM 8458 LOC478 homolog. .S1 a at 3.42E-04 9.36E-O3 O.βS (LOC478^9S); mRNA 00 495 yeast)
PRcDICTfcO; CSfiis similar to ramiiieris similar to
Cfa.12239. nbosorn3l protein L34 XM 5356 LOC478 ribosomal LSI at 3.30E-03 l.SSE-02 0.73 (UXT478509); mRMA 88 509 protein L34 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Ca,«is similar to famiHaiis similar to growth and growth and transformation transformatioivttepencient
Cfa.8972.1 protein <LOC4785β4); XM 5357 LOC478 dependent
-S1 at 5.S4E-03 i.ssε-02 0.7 mRNA 60 584
PREDICTED: Cams similar to famiiiaris similar to growth and
CfaAffr.18 growth and transformation -dependent transformation' 479.1. S1 s protein {L0C478S84}; LOC478 dependent.
JL ι.4βε-(κ 8.97E-O3 0.67 mRNA 60 mxnemr £81 protein vam — famiiiaris similar to
Cfe.12583. Y39AlA.21a XM 5357 LOC478 similar to 1.A1 at 5,396-03 ι.8iε-oa 0.74 (LOC47862Q), mRNA 94 620 Y39A1A.21a
similar to
PREDICTED: Cams NADH famiiiaris similar to NADH dehvdroqenas
CfeAffx.68 dehydrogenase (ubiquinon (ubiquinone) 1 beta e e) 3.1. S1 s a subcomplex; 5 XM 5358 LOC478 1 beta t 1.50€-03 1.25E-O2 0.74 (IOO17S639); mRNA 12 639 subcomplex, 5 similar to
Dvnein intermediate chain 2,
PREDICTCD: Cams famiiiaris similar to Dyn«ir cytosolic (DH irrtsrntediate <3iaiπ 2; iC-2) cytosolic (OH IC-Z) (Cytoplasmic (Cytopiasmk: dynein nein intermediate chain 2),
Cfa.6063,1 transcript variant 1 XM 5359 LOC478 intermediate
,A1 s at 4.63E-03 1.72E-02 0.76 (LOC478797); mRMA 61 797 chain 2) similar to
Dvnein intermediate chain 2,
PREDICTED: Cams famiiiaris similar to Dyneir cytosolic (DH intermetiiate chain 2; IC-2) cytosolfc (DH lC-2) (Cytoplasmic
CfaAffx.19 (CytopiasmK dynein dyn Irrtβrmediate Oiam 2), ein 713.1. S1 s transαipt variant I XM 5359 LOC478 intermediate at 4,S8£-(M l.OOE-02 0.74 (LOC478797); mRNA 61 797 chain 2)
PREDICTED: Canls similar to famiiiaris similar to histone
CfeAffx.19 I hlstone aminotransferase a 1 (predicted); transαipt minotransfer 878.1. S1 al variant 3 (LOC478799); XM 8449 LOC478
L 6.6S€-03 1.94E-0. 0.75 mm/K < Predicted i
PREDICTED: Csnls similar to faniiliaris similar to CBFl CBF1
CfaAHx.20 interacting corepressor int isoform 2; transcript eracting 465,1, S1 s VΛrtant 2 (LOC478804); XM 5359 LOC478 compressor at 3.5OE-03 1.58E-O2 0.7 mRNA 68 804 isoform 2 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000178_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to Brix domain
PREDICTED: Cams containing famillarts similar to Bπx protein 2 domain containing protan (Ribosome Z (Ribosome biogenesis
Cfa.10268. protein Sπx) XM 5365 LOC479 biogenesis
1.A1 s at 4.63E-03 IJZBOZ 0.76 (LOC479365); mRNA 04 365 protein Brix) similar fo
Glucose-6- phosphate jsornerase.
(GPl)
(Phosphogluc ose
PREDICTED: Cams isomerase) famillarts similar to (PGI) Glυcose-e-phosphate (Phosphohexo teomerase (GPE) (Pbosphoglucose se isomerase) tsomefβsa) (PGI) (PHl) (Pttosphohexose (Neuroieukin) isomerase) (PHl) (Neurotensin) ((^LK) (NLK) (Sperm
Cfa.1427,1 (Sperm antlgen-36) (SA- XM 8504 LOC479 antigen-36) Λ1 s at 6.94E-02 6,i3E-O2 0.68 36) (UX479379), mRNA 13 379 (SA-36)
PftEDICTED: Cams
CfaAf&<,24 famillarts similar to si CG32955-PO; lsoform D; milar to 477.1.S1 s transcript variant I XM 5366 LOC479 CG32955-PD, at 3.19E-03 1.54E-O2 0.76 (LOC479477); mRNA 14 477 isoform D
CKtUItI tU. WftiS si familiaris similar to milar to αa.18024. MAK31-:ike protein XM 5366 LOC479 MAK31-like LSI s at S.23E-04 l.OiE-02 0.73 (LOOi7948S); mRMA 26 488 protein
CfaAffx.29 FKEDICTturcanϊs famiiiβris similar to 250.1.S1 s OW646-PA (UX479563); XM 5367 LOC479 similar to at 4,026-06 6.686-03 0.73 mRNA 03 563 CG4646-PA similar to Cytochrome c oxidase subunit IV isoform 1. mitochondrial
PREDICTED: Cams familiaris similar to precursor Cytochrome c oxidase (COX iV-D suburslt JV βoform 1; (Cytochrome c mitochondrial precursor oxidas (COX JV-I) (Cytochrome e
Cfa.3121.2 c oxidase polypeptide JV) XM 5367 LOC479 polypeptide
,S1 S at 1.286-03 l,23E"02 0.77 (LOC479623); mRNA 59 623 JVi
CfaA!fx,30 famtllarts similar to similar to Protein KIM0174; 964.1.S1 S transcript variant I XM 5367 LOC479 Protein at 1.13E-03 l,20E"02 0.72 (LOC47%67); mRNA 98 667 K1AA0174 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famillarts similar to CG14977-PA; transcript
Cfa,10β33. valiant 2 (LOC479736); XM 8546 LOC479 similar to
1.A1 s at I.26C-02 2.S4E-02 0.76 mRNA 40 736 CG14977-PA famillarts similar to CGH960-PB; transcript
Cfa.1043.1 variant 3 (LOO479750); XM 8561 LOC479 similar to .A1 at 5.4:>E-03 1,S1E-O2 0.73 mRNA 70 750 CG14980-PB
PREDICTED: Cams
Cfa.3182,1 fβmiliaris similar to JTVl XM 5368 LOC479 similar Io .A1 at 4.846-03 1.75E-O2 0.7 (LOC4797S2); mftNA 80 752 JTV1
PREDICTED: Canls similar to familiaris similar to etotvσpk. yital integration ecotropic viral
Cfa.17019, site S (LOC4799S0); XM 5370 LOC479 integration site
1.S1 s at 6.236-02 5.76E-O2 0.67 mRNA 75 950 similar to T- complex
PREDICTED: Cams piotein 1. zeta familisris βimilsr to T- subunit (TCP-
CfaAHx.15 wmptex protein 1; ϊeVa 1-z (CCT- subunit (TCP-1-zeta) (Ca eta) 893.1. S1 s «eta) {ccr-j«t8'i} XM 8486 LOC480 zeta) (CCT- at -.126-02 2.41E-02 0.75 (UXHS0059); mRNA 87 059 zeta-1 ) similar to
Inner membrane protein
OXA1L. mitochondrial
PREDICTED: Cams precursor famillarts similar to Inner (Oxidase membrane protein OXAiL; mitochondria! assembly 1- precursor (Oxidase like protein) assembiy 1-lιkβ protein} (OXA1-like tOXAl-Sike protein) prot (OXAiHs) (Hsa); ein)
Cfa.1499.1 transαipt variant 1 XM 5373 LOC480 (OXA1 HS)
.A1 at ..2Sε-02 2.486-02 72 (LOC4S0239); mRMA 62 239 (Hsa) similar to
PREDICTED: Canis maonesium- ftimiliaris sitiiilar to deoendent magnesium-dependent
Cfa.1618β. phosprtaSase-l XM 5373 LOC480 phosohatase-
1.A1 at 4.39E-03 1.69E-02 0.7 (LOC4δ0264); mRMA 88 264 1
PREDICTED: Canls
CfeAffx,27 familiaris similar to heat si shock protein 1; alpha; milar to heat 629.1. S1 S ϋanscript variant 1 XM 5375 LOC480 shock protein at 2.02E-04 9.06E-03 0.6S (LOC4S043S); mRMA 57 438 1, alpha
PREDICTED: Cartis famillaris similar to heat similar to heat shock protein 1; alpha;
Cfa.293.1. transσipt variant 3 XM 8634 LOC480 shock protein
S2 at 3.80E-04 9.61E-03 0,73 (LOC480438); mRNA 95 438 1 , alpha Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to lmportin alpha
2 subunit
PReOICTED'. Csnls familiaris similar to (Karyopherin tmportin alptis-2 sυtwntt alpha-2 (Karycpherin alphs-2 subunit)
CfeAfJx.18 subunlt) (SSPJ -alpha; (SRP1-alDha) (RAG cohort protem 1); 054.1. S1 s transcript vsiisnt 3 XM 8569 LOC480 (RAG cohort. at 7.476-03 2.03E-O2 0.72 (10C480469); mRNA 28 469 protein 1 )
PREDICTED: Cams familiaris similar to AOP- si rtbosyiatlon factor 2; milar to ADP
Cfe.1871.1 transcript variant 1 XM 5376 LOC480 ribosylation
.S1 at 1.3.E-02 2.S8E-02 0.63 (LOC480437), mRNA 06 487 factor 2 similar to
PREDICTED: Cams chromosome
CfaAffx,25 famillarts similar to 17 op chromosome 17 open en 041-1.S1 S reading frame 37 XM 5376 LOC480 reading frame
3.68£-03 1.61E-02 0.72 (LOC480S32); mRNA 53 532 37 familiaris similar to
Cfa.10996, CS1833S-PA XM 5377 LOC480 similar to 1.A1 at 1.67E-05 7.SSE-03 0.73 (LOC4δ06δ5); mRNA 84 665 CG18335-PA
PREDICTED: Cams familiaris similar to 60S ribosomal protein L 12; similar to 60S
Cfa.795.1. transcript variant 4 XM 8577 LOC480 ribosomal A1 s at 3.49£-02 4.19E-02 0.77 {10O18Q716); mRNA 32 716 protein L12 similar to 78 kDa glucose- repuiateci protein precursor
(GRP 78)
(immunoglobu
PREDICTED: Cams familiaris similar to 7S lin heavy kDa ςlucose-reςuiatεt) chain binding protein precursor (GRP protein) (BiP) 78} (lmtnursoglobuliπ l>eavy ctwtin binding (Endoplasmic protein) (BIP) reticulum (Endoplasmic reticulum lumertal lumenal Ca{2-r) tending proton gφ78); transcript Cal2+)
Cfa.20174. variant t (LOC4S0726); XM 5378 LOC480 binding
1.S1 at ..4SE-02 2.68E-02 0.76 mRNA 47 726 protein orp78) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to 78 kDa Qlucose- requlated protein precursor
(GRP 78)
Ommunoqlobu
PREDICTED: Canis familiaris similar to 76 lin heavy kDa glucose-reguiated chajn.bjndina.. protein precursor (GRP protein) (BiP) 78) {ftriFiunotiiobulio heavy dusin binding (Endoplasmic proton) (SiP) reticulum (Endoptesmic reticulum lumenal
CfaAlix.30 lumenal Ca{2+) binding protein grp7S); transcript Ca(2+) 936.1.S1 s vβnsnt 1 (LOC480726); XM 5378 LOC480 binding at 4.6SE-03 1.73E-O2 0.75 mRNA 47 726 protein grp78) similar to
PREDICTED. Cams Cytochrome c- fβmiliaris similar to type heme Cytochrome c-type heme lyase (CCHL)
CfaAfix.18 lyase (CCHU) (Hoiocytochro (Hclocytochrome c-t^pe 006.1.S1 s ssΗϋiase) (LOC480S34); XM 5379 LOC480 me c-lvpe at 1.90E-03 1.32E-O2 0.76 mRNA 50 834 synthase) similar to NADH- ubiquinoπe
PREDICTED. Cams oxidoreductas fβmillarts similar to NADH e MWFE ubiquinone subunit
CfaAffr.33 o*idθf«tuct«ι$« MWFE (Co subuπft (Comptex h mplex I- 0.1.S1 s a MWFE) {CI-MWFE} XM 5381 LOC481 MWFE) (Cl- t 9,S6fc-W i.xfet-oa \:n (LOC48.U33); mRMA 55 033 MWFE) similar to πudix
PREDICTED. Cams (nucleoside famtllarts similar to oudix diphosphate
CfaAfix.48 (nucleoside diphosphate link linked moiety X)-type ed moiety 69.1.S1 $ motif 21 (i.OC4βl8δO); XM 5390 LOC481 X)-type motif at 2.13E-03 1.36E-02 0.76 mRNA 01 880 21 similar to
CfaAffttJS PREDICTED: Canls s familiariδ similar to small mall nudear 36.1.S1 s nuclear πboπucteoproteifi XM 5391 LOC481 ribonucleoprot at 3.30E-04 9.286-03 0.72 02 (LOC4S1991); triRNiA 12 991 ein D2
CfaAffx,19 PREDICTEDT CanS farwlians similar to 604.1. S1 x CGl 7059- PA XM 5394 LOC482 similar to at 1.54E-03 1.26E-02 0.67 (LOC4S2354); mRNA 71 354 CG17059-PA similar to
PREDICTED-. Cβπls olfactory familiaris similar to
CfaAffx.46 Olfactory' receptor Olr059 XM 5395 LOC482 receptor 04.1.S1 at ISSE-(M 9.00E-03 1.31; (LOC4S2435), mRMA 52 435 Olr859 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famiiiBrts similar to IKK similar to IKK
CfaAffx,10 I interacting protein isoform 2; transcript interacting 775,1, S1 ai variant 3 (LOC4S2619); XM 8613 LOC482 protein t S.20E-03 1.79E-02 OJS mRNA 59 619 isoform 2
PREDICTED. Cams similar to
CfaAffx.15 famlllarts similar to PGFRt oncogene partner 2; 171.1.S1 s transcript variant 5 XM 8519 LOC463 oncogene at 4.3βe-03 1.69E-02 0.74 (LOC4β31ϊl), mRNA )artner 2
PREDICTED: tans si familiaris similar to milar to
Cfa.12195, Mistøne M2B 2SlB XM 5402 LOC483 Histone H2B 11. A1 at 2.9OE-02 371E-02 0.7<? (IOC4S3164); mRNA 82 164 291B
CfaAffx.17 I PREDICTED: Cams familiaris similar to H2B similar to H2B 974.1.S1 ai hstoπe family; meinbef P XM 5402 LOC483 histone family. t i i.ise-02 2.43E-O2 0.62 (LOC483173); mRNA 91 173 member F
similar to Histone-lysine methyltransfer ase. H3 lysine-
9 specific 4 (Histone H3- K9_ methyltransfer
PREDiαED: CaniS familiaris simitar to ase 4) (H3-K9- Histone-lysine N- HMTase 4) nvethylttafisferase; H3 (SET domain lysine-^ specific <t bifurcat (Histone H3-K9 ed 1) meϋiyltransfcrase 4) ι,B3- (ERG- K9-HMTase 4) (SET associated domain bifurcated 1) prot (ERS-assoeiated protein ein with
CfaAHx.75 with SET dot^ain) (ESET) XM 5403 LOC483 SET domain) 9.1.S1 at 8.43E-03 2.Ϊ4E-02 076 (LOC483136); mRhU 04 186 (ESET)
PREDICTED: Canis similar to ftimiliaris similar to DUF729 DUF729 domain
CfaAffr.13 containing I XM 541 1 LOC483 domain 24.1.S1 at i.S9£-02 3.07E-02 0.73 (LOC483997); mRMA 14 997 containing 1 familiaris similar to Zinc si finger protein 432; milar to Zinc
CfaAffr.50 transcript variant 8 XM 8580 LOC484 finger protein 95.1.S1 at 3,0JE-(M 9.2Sε-03 0.73 (LOC484330), mRNA 41 338 432
CfaAffx,74 PREDICTEtJTCanS si familiaris similar to milar to 60.1.S1 S tripartite motif protein 39 XM 5422 LOC485 tripartite motif at 4.87E-04 l,00E»02 .35 (LOC48514.); mRNA 59 141 protein 39 famlllarts hypotheticβl UX55004; transcript
Cfa.11764. variant t (IOC48S2U): XM 5423 LOC485 hypothetical
1.A1 at 4.5?e-02 4.S4E-O2 0.76 mRNA 29 211 LOC485211 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000184_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000185_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED- Canls similar to
CfaAffr.10 I familiβriε sirwlβr to olfactory olfactory receptor 408.1, S 1 ai OirtOO. (LOC606771): XM 6431 LOC6Q6 receptor t tssε-02 3.006-02 1.34 mftNA 61 771 Olr1002 similar to
PREDICTED: CartiS signal
CfaAffx.14 I familiaris simitar to signal s sequence receptor; equence 005.1.S1 ai gamma (LOCS06368) XM 8433 LOC606 receptor, t i 2,66E-(M 9.116-03 0.76 mRNA 38 868 aaj2MES
KKtUIi. i tυ: cams si femillarts similar to milar to
Cfa.14458. thioredoxiπ-like 5 XM 8435 LOC607 thioredoxin- 1.81 s at 5.746-03 1.S4E-O2 0.74 (LOC607009); mRNA 22 009 like 5
PREDICTED: Cams similar to Iq
CfaAffx.26 familiaris similar to Ig la lambda chain V-I iegion mbda chain 5.1. S1 s a SL2 precursor XM 8435 LOC607 V-I region BL2 t 2.eee-02 3.75E-O2 0.75 (LOC607020); mRNA 51 020 precursor
PRcDICTfcO; CSfiis hypoth famiiisris hypothetical etical
Cfa.17890. prot«n UX607J61 XM 8437 LOC607 protein LSI at 4.37E-02 4.73e-02 0.77 (LOC607161); mRNA 62 161 LOC607161 similar to Prefoldin
PREDICTED: Cams subunit 5 (C- familiaris similar to mvc binding Prefoidin subunit 5 (C- protein Mm-1 ) myc blndιr>9 protein Mm (Mvc l) (Hyc ntoduiator i)
Cfa.729.1, (EIG'l); transcript variant XM 8531 LOC607 modulator 1 ) A1 at 2.496 02 3.49E-O2 0.7S 3 (LOC607260): mRNA 05 260 (EIG-Il familiaris similar to similar to peptidyfproiyl itionierase A ewform 1; tranecrlpt peptidylprolyl
Cfe.16324. variant 1 (LOC607390); XM 8442 LOC607 isomerase A 1-S1 s at 7.0i£-02 6.16E-02 0.75 mRNA 47 1
I' MBlC I 'CU '."CBnTS******"
CfaAffe(,12 familiaris similar to cell si division cyde 42; milar to cell 195.1.S1 S transcript variant 2 XM 8442 LOC607 division cycle at 3.34E-04 9.6tε-03 0.74 (.OC607429); mRNA 51 429 42 similar to Ig
CfaAfftc.22 I PREDICTED: Canls la familiaris similar to Ig mbda chain 275.1, S 1 ai lambda chain V-IV region XM 8441 LOC6Q7 V-IV region I I ..156-02 2.426-02 1.3 Sau (IOC607441); n-RNA 12 441 Bau
PREDICTED: Canls similar to familiaris similar to cytochrome
CfaAffx.11 I cytochrome RSO; famify P450. fa 4; subfamity v; mily 967.1.81 ai polypeptide Z XM 8442 LOC607 4. subfamily v,
L 5.246-03 1.79E-O2 0.71 (LOC607SΛ8); mRNA n polypeptide 2 femillarts similar to nucleolar protein S; similar to
Cfa.15096, transσipt variant 6 XM 8540 LOC607 nucleolar
LSI s at l.i4€-03 1.20E-O2 0.711 (LOC607667); mRNA 35 667 protein 5 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famillarts similar to si nucleolar protein S; milar to
Cfa.3436,1 transαipt valiant 6 XM 8540 LOC607 nucleolar .51 at 2.S8C-02 3.S6E-02 0.72 (LOCS07667); mRNA 35 667 protein 5 famillaris similar to CG16675-PA; transcript
Cfe.18525. variant t (LOC607697); XM 8434 LOC607 similar to 1,81 at 9.UE-02 7,tSE-O2 0.76 mRNA 30 697 CG18675-PA
PREDlCTED: Canls similar to familiaris sirrsilar to chromosome chromosome 3 open 3 op reeding frame 10; en
CfaAffx.86 transcript variant 2 XM 8563 LOC607 readinα frame 71.1.S1 at 2.7S6-02 3.68E-O- 0.71 (IOC607701); mRNA 99 701 10
PREDICTED: Canls similar to famiiisris similar to chromosome
CfaA1fκM chromosome 3 open reading fiame 10; 3 open 71.1.S1 s transcript variant 2 XM 8563 LOC607 reading frame at ..53E-02 2.77E-02 0.75 (LOC607701); mRNA 99 701 10
CfaAffx.30 PREDICTED: Cams famillaris similar to 6CS similar to 60S 96.1.S1 x ribc50inal protein L37a XM 8436 LOC607 ribosomal at 6.136-02 5.71 £-02 0.73 (LOCS07732); mRNA 18 732 protein L37a
CfaAfϊx.17 KKtmt i tu: Wftis hypothetical familiaris nvpoOietoi 330.1.S1 s proton LOC607913 XM 8447 LOC607 protein at 8.43E-02 6.85E-O2 0.76 (LOC607913}; mRNA 68 913 LOC607913 similar to THO complex subunit 4 (Tho4) (Ally of
AML- 1 and
PREDICTED. Cams LEF-D famillarts similar to THO complex suburm 4 (Tho4) (Transcription (AISy of AMU-I and LEM) al coactivator (Transcriptional Alv/REF) coactlvatw Aly/REI*) (bZIP enhancing factor (bZiP
Cfe.18383. BEF) (LOC607MS}; XM 8448 LOC607 enhancing
1.S1 at S.62E-03 2.176-02 0.7 mRNA 15 factor BEF) similar to THO complex subunit 4 (Tho4) (Ally of
AML-1 and
PREDICTED: Canls LEF-11 familiaris similar to THO complex subunit 4 (Tho4) (Transcription (Alsy of AML-I and LEM) al coadivator (Transcriptional Alv/REF) coactivator Alv/REF} (bZIP (bZIP enhafKing factor
CIa.18383. BEP) (LOC6079<lδ); XM 8448 LOC607 enhancing
1.S1 s at i.<t0E-02 2.67E-02 0.73 mRNA 18 948 factor BEF) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to THO complex subunit 4 CTtKA) (Ally of
AML- 1 and
PREOICTED-. Caπls LEF-D ramiliaris similar to THO (Transcription complex suburtft 4 (Tho4) (Ai'y of AML-I ami LSM) a\ coactivator (Transcriptional Aly/REF) reactivator Atv/REF) (b2IP (bZIP entwicirtg factor
CfaAfftc.97 BEF) (LOC607948); XM 8448 LOC607 enhancing 65.1.S1 at 3.206-02 3.98E-O- 0.73 mRNA 18 948 factor BEF)
PREDICTED: Canls similar to heat famiiisris similar to heat shock 7OkD shock 7OkD protein prot binding protein; transcript ein
Cfa.1050.3 variant 3 (LOC607960); XM 8444 LOC607 binding
■S1 at 4.34€-0<* 9.78E-O3 0.71: mRNA 01 960 protein
PREDICTED-. Caπls similar to heat familiaris similβr to heat shock 7OkD
CfaAffx.25 shock 7OkD protein prot binding protein; transcript ein 82.1.SI S variant 4 (LOC607960); XM 8538 LOC607 binding at I.34E-02 2.61E-O2 0.73 mRNA 27 960 protein similar to
PReDlCTED: Canis chaperonin
CfaAf*x.β7 familiaris similar to containing criβperonin oontβminς 3B.1.S1 s TCPl; subunit 2 XM 8448 LOC607 TCP 1. subunit at i.SlE-02 2.75E-02 0.69 (UX607972); mRMA 41 972 similar to Splicing factor
PREDiαED: Canis 3A subunit 3 familiaris sirn'lar to (Spliceosome Splicing factor 3A subuπtt associated 3 (Spiiceosoms prot associated protein 61) ein 61 )
Cfa.3337,1 (SAP 6t) (SF3360) XM 8448 LOC607 (SAP 61 )
.A1 at B.70E-03 2.176-02 0.64 (LOC607999); mRNA 87 999 (SF3a6Q)
PREDICTED. Cams familiaris similar to 4OS similar to 4OS
CfaAffx.45 ribcsoma! protein S2 XM 8449 LOC608 ribosomal 78.1.S1 at 7.87£-03 2.07E-02 1.3 (LOC60802S); mRNA 21 028 protein S2 f KCDILI tL): t_anss similar to tamiliβris similar to
Cfa.12239. ribosomal protein U4 XM 8450 LOC608 ribosomal 1.S1 s at 9.S3E-04 1.166-02 0.72 (LOC608033), mRMA 40 033 protein L34
PREDICTED: Cams similar to Non- farmllaris similar to Non- muscle musde caldesmon (CDM) cald (L-caictesrnon); trβiisctipt esmon
Cfa,16980, variant 2 (LOC608135); XM 8S47 LOC608 (CPM) (L-
2.S1 at 5.06E-03 1.77E-02 1.3Ii mRNA 87 135 caldesmon) similar to
CfaAffx.74 PREDICTED: Cams diaz familiaris similar to epam 7.1.S1 s a diazepam binding inhitntcx XM 8450 LOC608 binding t 3.1SE-03 1.S3E-02 0.57|(LOC608150); mRNA 72 150 inhibitor Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to
Ssu72 RNA
PREDICTED: Cams polymerase Il
CfaAfftc.75 familiariδ similar to Ssu72 CTD RNA polymerase JI CTD 81.1.S1 s phosphatase homofog XM 8452 LOC6Q8 phosphatase at 2.77E-03 1.48E-02 1S (LOC6GS299); mftNA 79 299 homoloq
PREDICTED. Cams similar to
CfeAfix.19 famiilaris similar to olfactory olfactory receptor
568.1. S1 x Olrl347 (LOC608416); XM 5346 LOC608 receptor.
JL s.ieε-03 1.79E-O2 1.33 mRNA £. 416 Olr1347 hypothetical familiariδ κyρotn«Scal
Cfa.3342,1 protein LOC60S59? XM 8456 LOC6Q8 protein .A1 s at 2.166-03 1.37E-02 '<5 (LOC608597); mRNA 66 597 LOC608597
PREDICTED: Canis similar to ADP
CfaAffx.25 I fβimiliaris similar to AOP- ribosviation- ribosy!atwn-lικe factor 12 261.1.Si ai protein; transcript variant XM 8465 LOC608 like factor 12 t 6J4E-03 X.Siε-02 0.73} 1 (LOC608600); mRNA 51 600 protein si
PREDICTED-. Cβπls milar to famiiiβris similar to eukaryotic eukaryotie translation translation
OaAffx.28 termifiatiofi factor 1 t (predicted); transcript ermination 14.1.51 s variant 4 (LOC608717); XM 8583 LOC608 factor 1 at I.3δε-04 6.9OE-O3 0.69 mRNA 85 717 (predicted) similar to single-
PREDICTED: Cams stranded DNA famiϋarls similar to stngle- binding strartded DNA binding
Cfe.10101. protein 1 lsoform 1 XM 8458 LOC608 protein 1
1.A1 s at 3.Ϊ5E-CW 9.2SE-O3 0.69 (LOC608727); mRNA 39 727 isofonn 1 similar to 4OS ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma
PREDICTED: Canis binding familiariδ similar to 4OS protein) ribosomal protein SA (p40) (34/67 kOs Wmlnin (NEM/1CHD4)! receptor) (Colon (Multidrug carcinoma laminm-feinding resistance-
CfaAI8c.11 I protein) (NEM/1CHW) (Multidrug resistance- associated
16ai,S1 al associated protein MGrI- XM 8460 LOC608 protein MGrI- t 4.23E-03 1.68E-02 0.67 Ag) (LOCS08876); mRMA 11 876 Ao] Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to 4OS fibosomal protein SA (p40) (34/67 kDa laminin receptor) (Coion carcinoma laminin-
PREDICTED: Canls familiaris similar to 4OS protein) ribβsomal μncrteln SA (p40) (34/6? kOa laminirt (NEM/1CHD4) receptor} (Coion (Multidrug carcinoma lamimn-binding resistance-
CfaAffx.32 protein) (NEM/1CBD4) associat (Mutttdwg resistance- ed 2.1.S1 x a associated protein MGfI- XM 8460 LOC608 protein MGii- t 2J7E-03 I.40E-OZ 0.73 Ag) (IOC608876); mRNA 11 876 Aa) similar to SET protein
(Phosphatase
2A inhibitor 12PP2A) (I- 2PP2A) (Template activating factor H (TAF-
PREDICTED: Canls I) (HLA-DR familiaris similar to SET associated proton (Phosphatase 2A protein II) Inhibitor 12PP2A) (E- 2PP2A) (Template (PHAPH) activating factor I) (TAF- (Inhibitor of r) (HU-DR associated αranzvme A- protein U) (PHAPH) activat (inhibitor of grerwyme A' ed
Cfa.11306. activated DNase) (JGAAO) XM 8461 LOC608 DNase) 1.A1 s at i.røε-02 2.386-02 0.72 (LOC60S952); mRNA 14 952 (IGAAD)
CfaAfix.14 KKtWtI tL): <-«sn:s famiiiaris similar to
119.1.S1 s CGlS(Ml-PA XM 8462 LOC609 similar to at 7,77E-M l.iOE-02 0.75 (LOC609028); mRNA 08 028 CG 18041 -PA
CfeAffx.25 PREDICTEDTXa?«S famlllarts similar to S48.1.S1 s prohitatm (IOC609(MJ); XM 8462 LOC609 similar to
1.336-04 8.9OE-O3 0.7 mm/K jrohibitin
CfaAfftc.26 i PKtDiCTtD: tanTs hvpoth famiiisns nypometicai eticai 274.1.S1 ai prot«n UX6090SO XM 8462 LOC609 protein t i 2.366-03 1.406-02 1.33 (LOC609090); mRNA 92 090 LOC609090
KKtWtI tL): <-«sn:s fβimiliaris hypothetical hvpotheticai
Cfa.17614, piOtein LOC609036 XM 8463 LOC609 1.S1 at 2.13E-02 3.24E-02 072 (LOC609096), mRI^A 01 096 LOC609096
CfaAffx,β2 KKtUIi. i tυ: cams hypothetical fβmillarts hypothetical 87.1.S1 s protein IOC6090% XM 8463 LOC609 protein at 3.176-03 1.S4E-O2 0.76 (LOC6090%); mRNA 01 096 LOC609096 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000191_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to TATA box binding protein-like protein 1 (TBP like protein 1 )
PREDICTED: Canls (TATA box famiiisris similar to TATA binding box binding proteiπ-fite protein 1 (TSP-like protein-related proton I) (TATA bOX factor 2) (TBP- binding protein-related related factor factor 2) (TβP-retateeS factor 2) (21-tcOa TBP-liioe 2W21»kDa
Cfa.19736. protein); transcript varian! XM 8612 LOC609 TBP-like
1.81 s at 4.27E-03 1.6SE-02 0.73 3 (LOC609509); mRNA 95 509 protein) familiaris similar to
Cfa.14095. CG17680-PA XM 8469 LOC609 similar to LSI s at 2.9SE-03 1.50E-O2 0.6^(LOC60%43); mRMA 40 643 CG17680-PA similar to
PR6D1CTED-. Canls MHC class Il famiiiβris similar to MHC r :lβss JI region expressed eoion
Cfa.4311,1 gene KE2 (LOC609675); XM 8464 LOC609 expressed
.A1 at I.74E 03 1.3OE-O2 0.77 mftNA 63 675 gene KE2 similar to GC-
PREDICTED: Cante rich sequence fβmiliails similar to GC- DNA-binding rich sequence DNA- bifiding factor homolog XM 8470 LOC609 factor
3.1.81 at 6.39ε-04 J.05E-O2 0.66 (IOC6097*)); mRNA 66 740 homoloq
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to Proteasome activator complex subunit 1 (Proteasome activator 26- alpha subunit) (PA28alpha)
(PA28a) (Activator of
PREDICTED: Cams multicatalvtic famϋiaris similar to protease Proteasome activator comptex subunit i subunit 1 ) (Proieasome activator 28- (11 S regulator alpha subunit) complex alpha (PA23_lptø) (PA2Sa) (Activator of multlcatalytSc subunit) (REG- protease subunit 1) (IiS alpha) reoυlstor complex alpha (Interferon
CfaAf6t,39 subunit) (REG-alpha) ga (Interferon gamma up- mma up- 27.1.S1 S regulated 1-51 u p,.. XM 8470 LOC609 regulated I- at 5.25E-03 1.79E-02 0.62 (_OC$09?63); mRMA 95 763 5111 p... similar to
Alcohol dehvdrogenas e class III chi
PREDICTED: Cams famiiisris similar to chain Alcohol dehydrogenase (Glutathione- dsss 211 ehi chain dependent (Glutattitone dependent for formaicehyde maldehyde
Cfe.10530, dehydrogenase) (FDH) XM 8471 LOC609 dehvdrogenas
1.A1 at 6.0Sε-03 1.87E-02 0,75 (LOC6O978.); mRNA 20 781 e) (FDH) similar to
PREDICTED: Canls Ferritin light
CfeAffx,66 familiaris similar to Ferritin light chain 1 chain 1
01.1.S1 x {Ferritin i. subunit 1) XM 8471 LOC609 (Ferritin L
3.73E-04 9.61E-03 1.S6 (LOC609811); mRNA 811 subunit 1 )
CfaAffr.27 PREDICTCD: Cams similar to familiaris similar to
166.1. S1 ai nudear RNA export fector XM 8471 LOC609 nuclear RNA
1.S4C-03 1.23E-02 Ul: 2 (LOC609814); mRNA 53 814 export factor 2
CfaAHx.26 PREDICTED: tans si familiaris similar to milar to
687,1, S1 ai olfactory receptor 464 XM 8473 LOC609 olfactory
3.096-03 1.53E-O2 1.33 (LOG6Q996-); mRNA 16 961 receptor 464 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to
Cytochrome c
PREDICTED: Cams oxidase familiaris similar to polypeptide
CfaAlix.19 Cytochrome c oxidase VHc. polypeptide VJIc; 061.1.S1 S mitochondrial precursor XM 8473 LOC609 mitochondrial at 3,78C-OS 7.SSE-O3 0.66 (LOCS09990); mRNA 63 990 precursor similar fo
Transcription initiation factor TFiID subυnit 12.
PREDICTED: Canis (Transcription familiaris similar to initiation factor Transcription initiation TFHD 20/15 factor TFJlD subumt 12 (Transcription initiation kDa subunits) factor TRID 20/15 XOe (TAFM- subunits) (TAFπ-20»TAFU 20/TAFIJ-1S) IS) (TAFH20/TAl=ϊnS};
Cfa.10041. transcnpt vsrisnt 2 XM 8472 LOC609 (TAFI I20/TAF1
1,81 s at 7.86E-03 2.07E-02 0.72 (LOC609994); mRNA 49 994 115)
CfeAffx.29 CKtuititu.' wrtis fβmiliaris similar to 414.1, S1 ai CG7338-?A (IOC610CMS); XM 8474 LOC610 similar to
2.44E-03 1.4IE-02 0.76 mRNA 38 048 CG7338-PA
similar to Proteasome subunit alpha type 1 (Proteasome component Cl)
(Macropaiπ subunit C2)
PftEDICT€D: Cams farmliaris similar to (Multicatalytic Proteasome subunit alpha endopeptidas type 1 (Pfoteasome e complex component C2) (Maσopam sυbunit CZ) subunit C2) (MulticatalytK (Proteasome endσpeptidasβ complex nu chain) (30 subunit C2) (Proteasome kDa proso nu cnaiπ) {30 kDa mai
Cfa.11083. prosomai protein) (PROS- XM 8476 LOC610 protein) 1.A1 s at 2.17E-03 1.37E-02 0,73 30) (LOC610188); mRNA 20 188 (PROS-30)
PREDICTED: canis hypoth familiaris nypotnetical etical
Cfa.9169,1 protein LOC650216 XM 8476 LOC610 protein
3.3«ε-03 1.56E-O2 0.69 (LOC6S0216); mRNA 216 LOC610216
CfaAf6t,23 PKcDiCTtϋrcsπis familiaris rsypoCietJcal hypothetical 970.1.S1 s protein UX610210 XM 8476 LOC610 protein at 164E-03 1.28E-02 074 (LOC610216), mRMA 55 216 LOC610216 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000195_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
similar to Eukaryotic translation initiation factor
.4E.type 3. (elF4E tvoe 3) (elF-4E type
3) (mRNA cap- binding
PREDICTED: Canls protein type 3) familiariδ similar to (Eukarvotic Eukaryotsc translation Initiation factor 4E type 3 translation (elRE type 3) (elME initiation factor type 3) (mRNA cap- 4E-lιke 3) binding protein type 3) (EuKaiyotlc translation (Eukaryotic initiation factor 4E-llke 3) translation (Eultaryotlc translation initiation factor initiation factor 4E homologous ptxrtβln) 4E.
Cfa.11431, (mR... (LOC61121S); XM 5346 LOC611 homologous
1.A1 at ..5S£-03 1.26E-O2 0.68 mW.'A 06 215 protein) (mR...
similar to Adapter- related protein complex 1 siαma 1B subunit (Siαma- adaptin 1B)
(Adaptor protein complex AP-1 sipma-1B subunit) (Goigi
PREDICTED: Canis adaptor ftimiliaris sitiiilar to HA1/AP1 Adapter-neiated protein comptex 1 sigma IB adaptin sigma- sυbυrat (Sigma-adaptin 1 B subunit) IB) (Ariaptat protein (Clathrin comptex AP-I sigma-lB subunit) (Goigi adaptor assembly HAl/ API adaptin sigfna- protein IB subunit) (Clatlvin complex 1
CfaAffx.16 assembiy protein complex siq 1 sigma-lB small chars) ma~1B 992.1.S1 s (Sigma .6 s... XM B491 LOC611 small chain) at 2.S9E-02 3.77E-02 0.76 (LOC6I1468); mRNA 37 468 (Sigma 1B s. Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000197_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000198_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PKEDICTcD; PiBCaCa hypoth mulatta hypcthetica! etical
CfaAftxJβ protein LOC70W! XM 0011 LQC704 protein 02.1.S1 at s.2oe-O4 1.1 $£-02 0.74 (IOC7CW974); mRNA 974 LOC704974 similar to
PREDICTED: Macaca chromosome mulatto similar to 1 open chromosome i open r reading frame 9 μfotein eading frame
Cfa.931.1. asofβrm 1 (LOC705776); XM 0011 LOC705 9 protein A1 at I.17E-02 2.4sε-oa 0.74 mRNA 00732 776 isoform 1 nwlatta similar to similar to mitochondrial earner tnpie repeat 1; transcript mitochondrial
Cfa-11241. variant J (LOC706278); XM 0010 LOC706 carrier triple 1.A1 at 4.SSE-03 1.72E-02 0.7S mRNA 99530 278 repeat 1 similar to Adrenodoxin, mitochondrial
PREDICTED: Macaw mulatta simliar to precursor Adrenodoxm; (Adrenal mitochondrial pfβcursor ferredoxin)
CfaAffx.21 (Adrenβl ferredoxiπ) (F (Ferredoxln-J) erredoxin-1) 9S2.1.S1 s (htepatoredoxin) XM 0011 LOC709 (Hepatoredoxi at 1,57E-OS 7.SS6-03 0.7 (LOC709II0), rc.RHA 05034 110 n_
CfaAf&(.24 i
PREDICTED: Macaca 141.1.S1 ai muiβtta sifrtiar to RCCi- XR 01260 LOC712 similar to t ! 2.46E-04 9.06E-03 0,73 like (LOC712305); mRNA 305 RCC 1 -like rfccorcrrrrwercβrtr mulatta sirraiar to egl nine similar to eαi homolog l; traascnpt
Cfa.10226. variant 2 (IOC7.3-U0),: XM 0011 LOC713 nine homoloα 1.A1 at 4.60€-02 4.86E-02 0,77 mRNA 04870 410 1 mulatta hypothetica! protein IOC7545S6; hypothetical
Cfa.14782. trariKfipt variant J XM 0011 LOC714 protein LSI a at 3.166-02 3.96E-02 0.6 (LOC7WS86); mRNA 11772 586 LOC714586
PREDICTED-. Macacs muiatta similar to similar Io phosphaSdyiinosito! phosphatidyl^ gtycβπ ciass V; transcript
Cfa.10431, variant 9 (LOC7H898); XM 001 1 LOC714 ositol qlycan
1.A1 a at ..26E-02 2.51E-O2 0.72 mRNA 10112 898 class V
PREDICTED. Macaw similar to
CfaAffx,26 mulatta simliar to Protein Protein Ctorf77 homolog; 816.1. S1 s transcript vsrisnt 3 XM 0011 LOC715 C1orf77 at 2.38E-03 l,-WE"02 0.76 {LOC715SO.); mRNA 11616 501 homolog
PREDICTED: Macaca mulatto sirrtiar to similar to
Cia.19566. homolog of yeast MON2 XR 01452 LOC716 homolog of 1.S1 at 1.846-03 1.31E-O- 0.75 {LCC716872); mRNA 1 872 yeast MON 2
PREDICTED: Homo sapiens simiiar to protein
Cfa.2344.1 x 013; transcript variant 3 XM 0011 LOC727 similar to
2.106-02 3.21E-O2 0.74 (LCC727778); mRNA 25757 ZZI protein x 013 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000200_0001
Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
faniiiiaris similar to
CfaAffx,21 leucine nth repeat containing 2; transcript leucine rich 185.1.S1 S variant 2 (LOC476647); XM 8593 repeat at Ϊ.20E-04 3.90E-O3 l.: S mRNA 31 LRRC2 containing 2
PKcDiCTtϋrcsπis familiaris similar to leucine rich
Cfet.2068.1 CG3040-PA (LOC478269); XM 5354 repeat ■S1 at 5.97E-03 1.67E-02 076 rnRNA 43 LRRC57 containing 57 leucine rich repeat containing 8
Homo sapiens mRNA for
Cfe,11684. KSAA143? pfotein, partial family,
1.A1 at 1.41E-03 l,24E-02 076 csis AB037858 LRRC8A member A
PREDICTED: Cams familiaris similar to U6 LSM1 snRNA-associated Stn-like homoloq. U6 protein LSttil (Smali small nuclear
CfaAffx.10 nυctear rfbonudear RNA CaSm) (Cancer-associated 169.1.S1 S Sm-iite) (LOC47SS87): XM 5328 associated (S, i.67E-03 1.29E-02 072 mRNA 06 LSM 1 cerevisiae)
LSM 14A.
Pft£DICTεD. Cams famlllarts similar to alpria oL<ϋo
Cfa.19032, synucleiπ binding protein XM 5337 homolog A (S,
LSI s at 1.19C-03 1.21E-O2 0.73 (LOC476Λ92); mRNA 01 LSM 14A cerevisiae)
LSM14A,
PREDICTED: Cartte SCD6 familiails similar to alpha
Cfa.2957,1 synuclein δindlng protein XM 5337 homolog A (S.
.A1 s at 3.796-03 1.63E-O2 0,77 (100176*92); mRNA 01 LSM 14A cerevisiae)
LSM14A.
PREDICTED: OmIs SCD6 familiaris similar to alpha
Cfa.3288,1 synuciein binding protein XM 5337 homolog A (S.
,A1 at 7.92E-04 1.10E-02 0,7 (LOC476492); mRNA 01 LSM 14A cerevisiae)
LSM6 homolog . U6
PREDICTED: Canis small nuclear
CfaAffx,12 ftimiliaris sitnilar to US RNA snRNA-assoc!ate-t Sm-llke 446.1.S1 s protein LSmδ XM 8500 associated (S,
6.3SE 03 1.91E 02 0.75 (LOC512329); mRMA cerevisiae)
LSM7 homolog. U6
PR601CTED: Cβnis small nuclear ftimiliaris sitnilar to US RNA snRNA-assooated Sm-llke
Cfa.8071,2 protein LSm7 XM 8499 associated (S,
,S1 a at I.66E-03 1.286-02 0.69 tU)CSS2i70); mRMA 02 LSM7 cerevisiae)
200 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
LSM8
PREDICTED: Cams homolog. U6 famillarts similar to U6 small nuclear snRNA-assoctated SrnHike RNA protein L&n8; tfanβcnpt
Cfa.20β53. variant 2 (LOC47S298); XM 8611 associated (S.
1.81 s at 8.S1E-03 2..8E-02 0.72 tnRNA 26 LSMS cerevisiae) farroliaris similar to IUC?- like isoform b; transcript
Cfa.21629. variant 2 (LOC479898); XM 8604 LUC7-like (S.
2.S1 s at 2.57e-02 3,S5E-O2 072 mRNA 39 LUC7L cerevisiae) familiaris sitiiilar to Lymphocyte antigen 96 precursor (MD-2 protein)
CfaAffx.81 (ESOP-.) (LOC610524); XM 8480 lymphocyte
6.1.S1 at 4.04£-03 1.656-02 0.72 roftNA 45 LY96 antigen 96 ftimiliaris similar to lysozyme-ijKe 6; tt-anseπpt
Cfa.3936.1 variant 2 (LOC480492); XM 8557 Ivsozvme-like ,A1 at 3.7SE-02 4.34E-02 0.76 mftNA 95 LYZL6
PREDICTED: Cartis famillaris similar to Mitotic spindle assembly checkpoint protein MAD2 mitotic HAD2A (MA02-!lke I) arrest (HsMAD-); transcript
Cfe.1844,1 vsiiatΛ 1 (LOC476070); XM 5332 deficient-like 1
.51 at I.58E-02 2.82E-02 0.73 wRNA 78 MAD2L1 (yeast) mapo-nashi
PREDICTED. Cams homolog, famillarts similar to Mβgo prolif nasrt: protein homolog; eration-
Cfa.11345. trariscnpt variant 1 XM 5367 associated
1.A1 s at 3.446-03 1.S7E-O2 0,66 (LOC479562); mRNA 02 MAGOH (Drosophila)
PREDICTED: Canis
CfaAffx.26 ! familiaris similar to impiantaborv-associβted 407.1.S1 ai protein; tyanscript variant XM 5490 magnesium t 4.00E-OS 7.SS6-03 0.67|l (I.OC491975); mRN.^ 95 MAGT1 transporter 1
PREDICTCD: Cams homolop, farroliaris similar to amino-acid N- corneal wound healing- acetyitransfer related protein; transcript
Cfe.97β0.1 variant 4 (LOC476304); XM 8512 ase subunit
-A1 at 7.21E-03 2.006-02 0.7 mRNA 02 MAK10 (S. cerevisiae)
PREDICTED: Canis famtliaris sitnilar to mucosa Mucosa associated lymphoid tissue associated lymphoma translocation lymphoid protein 1 (MALT- tissue
CfaAffr.11 lymphoma associated translocation) lymphoma 26.1.S1 β (Paraeaspase) XM 5333 translocation at 7.93E-03 2.08E-02 0,74 (LOC4761SS); mRNA 92 MALT1 gene 1 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED- Cants familiβriε sirwlβr to lass mannosttlas mannossdase; alpha; c e,
Cfa.10702, IA; member 1 XM 5334 alpha, class 1.A1 at 5.96ε-04 1.046-02 0.71! (UX47S275); mRNA 81 1A. member 1
PREDICTED: Cams familiaris sirrsilar to mannosadasc: alpha; class mannosidase,
Cfa.10702. IA; member I XM 5334 MAN1A alpha, class 2.A1 a at i.2Sε-03 1.22E-O2 0.75 (IOC-176275); mRNA 81 1 1A. member 1
Honio sapiens mRMA; cDNA DKrzp030111S29 mannosidase.
Cfa.9537.1 (from done alpha, class
,S1 at 1.616-03 1.31E-O- 0.73 DKFZp&86M1529) AL633486 2A. member 1
PREDICTED: Canls famiiisris similar to Micrctubule-assodated protein IB (MAP IB); microtubule-
Cfa.16571. transcript variant l XM 5352 associated
LSI s at 4.226-03 1.67E-02 IJl: (LOW78092); mRNA 69 MAPI B protein 1B
PREDICTED. Pan mitoαen- troglodytes rottogen- activated scavated protein kinase prot kinase kinase 2; transcript ein kinase
Oa.3055.1 variant 2 (MAP3K2); XM 0011 kinase kinase
,A1 at 1.08E-02 2.37E-O2 073 mRNA 37266 MAP3K2 2
PREDICTED: Equus mitoqen- catjallus mitogw- activated
CfaAffx,56 activated protein kinase prot kinase kinase 7; traπscipf ein kinase 42.1.S1 S variant 4 (MAP3K7); XM 0015 kinase kinase at S,S!E"04 1.02E-02 0.69 roftNA 03786 MAP3K7 7
PREDICTED. Cams mitooen- familiaris similar to activated mrtogen-activateo protein protein kinase kinase kinase kinase 7 kinas ιrttsr3<smg protein 2 e kinase
CIa.16190. isoform 1 {LOC4a4028>; XM 5411 MAP3K7 7 interacting
1.A1 at 8.10E-03 2,tOE-O2 0.73 mRNA 45 IP2 protein 2 mitocien-
CfaAffx.23
Cants lupus familiaris activated
■ 1.S1 al mitogen -activated protein NM 0011 protein kinase t 3,646-03 1.616-02 0.6^kinase I (MAPKl); mRNA 10800 MAPK1 1 mitogen-
CfaAfftc.23 activat
Canis lupus familiaris ed ■ 1.S1 S mrtogen-activated protein NM 0011 protein kinase at ..766-03 1.306-02 6 kinase t (MAPKl); mRNA 10800 MAPK 1 1 mitopen-
Canls førriitøfts p38 mitogen activated protein activated
Cfa.1239,1 kinase mRNA; complete protein kinase
,S1 s at i.826-03 1.31E-O2 0.7S αis AF003597 MAPK14I 14
202 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000204_0001
203 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000205_0001
204 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000206_0001
205 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
farrnllaris similar to Methionine amuiopeptidase 2 (MetAP 1) (Peptidase K 2) (Initiation factor 2 associated 67 kOa
CfaAffx.10 glycoprotein) (p67) (p67etF2); transcript methiotwl 510.1 -S1 s variant I (LOWS-WS); XM 8475 aminopeotidas at i.s?e-03 1.32E-O2 0.73 mSMA 59 e 2 familiaris similar to Hypothetical UPHHMS methyltraπsfer protetl ZK1128 2 in chromosome ItI; ase iO
Cfa.10266. transcript variant 2 XM 8634 METT10 domain
1.A1 at /.osε-04 1.08E-02 0.73 (10O18Q65S); mRNA 12 containing
PREDICTED: Equus cabalius mex-3 homotog mex-3
Cfa.2303.1 C (C. eSβgans) (MEX3C); XM 0019 homolog C (C,
,A1 s at 2.026-02 3Λ6E-O2 0.73 mRNA 16773 MEX3C elegans) famϋlarts similar to
CfaAffx,20 mltrofltjfillar-assoclated micfofibfillar- protein I; transcript 742.1.S1 S variant 2 (LQC478281): XM 8553 associated at 3.44E-03 1,S7E»O2 0.7S mSNA 67 MFAPI protein 1
PREDICTϊD: Canis
CfaAfftt,17 I fanύliβris similar to Transmembrane GTPβse 646.1.Si ai MFNl (MftofusJn-1) XM 5452
L 6.49E-04 i.osε-02 0.73 (LOC4S8086), mRMA U2 MFN1 mitofusin 1 maior
PREDiαED: Canis facilitator farmliaris simitar to CG18549-PA; trarxscrlpt superfamilv
Cfa.5250.1 vβnsnt 1 (LOC483336); XM 5404 domain
,A1 at 9.1SE-(M J.tSE-02 0.74 mRNA 55 MFSD11 containing 11 rarmϋans sιm:lβr to Aiptta- 1,'6-msnnosyi- glycoprotein 2-bβta-N- acetylgiucosaminySt'ansfe rase (Mannβstde scetylglυcosarninyltransfe mannosyl rase Z) (N-glycosyi- oligosaccharide- (alpha-1.β-y- glycβpfotβjn N- glycoprotein acetylgiucosaminyitransfe beta- 1.2-N-
CfeAflx.21 rase II) (Beta-.;2-N- acetylgluco-amiDySt'ansfe acetvigiucosa
875.1.81 s rase U)... (LOC4SO312); XM 5374 minyltransfera at 2.61E-03 1.44E-O2 0.77 mRNA 34 MGAT2 se famiiiaris similar to meningioma meningioma expressed expressed antigen 5 antigen 5 (hyalurβntctase);
Cfa.12884. tf adscript variant 12 XM 8572 (hvaluronidas
LSI at 4,77E-03 1.74E-02 0.7-» (LOC477802); mRMA 66 MGEA5 e} farmliarts similar to meningioma rrt3ntπ9θfπ<! expressed expressed
CfaAffit,15 antig^ S antig (fryaluronJdase); en 5 618.1.S1 s transcript variant 14 XM 8573 (hvaluronidas
JL 4.49E-03 1.71E-02 0.75 (LOC477802), mRMA MGEA5 &
206 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000208_0001
207 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
membrane
PREDICTED: Cams protein, familiaris similar to palmitoviated membrane protein; 6 (MAGUK pslfmtoyiβted 6; transcript
Cfa.19439. variant 2 (LOC482362); XM 8462 p55 subfamily
1.81 s at 3.92E-03 1.64E-02 0.76 mRNA 49 MPP6 member 6)
PR6D1CTED-. Csnls familiaris similar to mitochondrial ribosomβl mitochondrial
Cfa.11680. protein Llδ (LOC476898); XM 5341 ribosomal
1.A1 at 2.36E-03 1.40E-02 0.76 partial mRNA 01 MRPU 6 protein L16 familiaiis similar to
CfaAffx.10 I mitochondrial ribosorsial protein Li?; transcript mitochondrial 831.1 -S1 ai variant I (IOC5.0200); XM 8460 ribosomal t 6.026-04 1.04E-O2 0.77 mRNA 34 MRPU 7 protein U 7 familiaris similar to mitochondrial risosomal mitochondrial
Cfei.10307, protein LlS <LOC476260>; XM 5334 ribosomal
1.A1 s at 3.976-05 7.55E-O3 0.68 mRNA 65 MRPU 8 protein L18 familiaris similar to mitochondrial ri&osomal mitochondrial
CfaAffx.74 protesn LiS (LOC476260); XM 5334 ribosomal 4.1.81 at 2.496-04 9.06E-O3 0.7S mRNA 65 MRPU 8 protein L18
CfeAffx,29 familiaris similar to mitochondrial ri&osomal mitochondrial 394.1. S1 s protesn L20 (LOC47SS69); XM 5367 ribosomal at 3.72E-05 7.55E-O3 0.71i mRNA 09 MRPL20 protein L20
PREDICTED: Cams farmliaris similar to mitochondria! πOosorrvat mitochondrial
Cfe.5875.3 prøteln L22 isofoiw ct XM 5364 ribosomal
-A1 s at S.S36-03 1.8SE-02 0.7 (LOC479320); mRhU 58 MRPL22 protein L22 familiaris similar to mitochondrial ribosomal mitochondrial prot«n i.27; traπsαipt αa.15082. variant 4 (LOC491078); XM 6605 fibosomal
LSI a at 1.37E-04 8.90E-03 0.73 mRNA 18 MRPL27 protein L27
PREOlCTED. Cams
CfaAf{χ.δ1 familiaris similar to mitochondrial riSosomal mitochondrial 3.1 -S1 s a protein UO isoform a XM 5317 ribosomal t X.05€-03 1.19E-0- 0.74 (LOC474SSS); mRNA 86 MRPL30 protein L30
CfeAffx.23 familiaris similar to mitochondrial ribosorttal mitochondrial 692.1. S1 s protein L34 (LOC6t0t39); XM 8475 ribosomal
6.59e-03 1.94E-0. 0.75 mRNA 52 MRPL34 protein L34 familiaris similar to mitochondrial ribosortal mitochondrial
Cfa.16020. protein L36 (LOC4SS065); XM 5451 ribosomal
1.S1 s at 3.696-05 7,55E-OJ 0.71i mRNA 88 MRPL36 protein L36
PREDICTED: Cams familiaris similar to mitochondrial mitochondrial riaosomβl
Cfe,11000. prøtein L3S isofoirrc A XM 5448 ribosomal
1,81 s at 8.64E-CW l,t3E-02 0.74 (LOC487709); mRNA 33 MRPL39 protein L39
208 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000210_0001
209 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000211_0001
2J0 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Canis famsliaris similar to Mitochondria! carrier mitochondrial homotog 2 (Met-induced carri mitochondrial protein); er
Cfa-9192,1 tf adscript variant 6 XM 8552 homoloα 2 (C,
-A1 at ..S4€-04 9.006-03 (LOC475977); mRNA 49 MTCH2 elegans)
PREDICTED: Canis familiaris similar to Metal- metal response eiement-binΛng response transcription factor 2 element (MeUsl-fesμae&e e)em«)l DNA-binciing ptotein binding
Cfa.1889.2 M%); transcript variant 1 XM 5370 transcription
.S1 s at S.94E-03 1.86E-02 0.76 (LOM79M8); mRNA 73 MTF2 factor 2
PREDICTED: Cams familiariδ similar to Metal- metal response etement-bindifig response trsrtsCTipftion factor 2 element
CfaAffr,30 I (Metal-isspoxse etemet\t binding DNA-binding protein 853.1.81 ai H%); transcript variant 3 XM 8618 transcription
L 7.49E CM 1.09E -0Z 0.74 (LOC479948); mRNA MTF2 factor 2
PREDICTED: Canls familiaris siinilar to Metal- metal response ^emer>t-birκtιrsg response transcfSption factor 2 element (Metal-response eJement DNA-binding protein
CfB.1889.1 M96); transαipt variβftt S XM 8618 transcription
-A1 s at a.ooe-tw 9.06E-03 0.75 (LOC479948); mRhU 9Θ MTF2 factor 2 methylenetetr ahvdrofolate dehvdroαeπas e (NADP+ dependent) 1. methenyltetrø hydrofolate
PREDICTED: Cams cvclohvdrolas familiaris similar to C-t
CfeAfix.24 tebahydiofolate sytsttiase; for cytoplasmic (Ci-TMF myltetrahvd 531.1 -S1 s synthase) (UDC<tβO352); XM 5374 rofolate
3.38E-03 1.56E-0. 0.76 mm/K 76 synthetase methylenetetr
PREDICTεO: Cams ahvdrofolate farmliarts similar to dehvdroαenas methyteneteCrshydrorblat e <tehydrogenase (NA0P+ e (NADP-*-
Cfe.19689. cteper>dent) Mike XM 5334 dependent) 1 - 1.S1 at 1.23E-03 1.23E-O2 .36 (LOC476245), mRl^A 50 like familiarts similar to C0XG5.8; transcript mvotubularin
Cfa.20403. variant 4 (LOC479017); XM 8516 MTMR1 related protein
1.S1 a at 1.66E-02 2.89E-02 1.32 mRNA 34 15 familiarts similar to Myotubuiaππ-related mvotubularin
Cfe.18355. protein δ (LOC477336); XM 5345 related protein
1.81 at S.426-(M 1.O2E-O2 0.66 mRNA 30 MTMR6 6
2J l Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000213_0001
2J2 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000214_0001
2J3 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PRK)ICTgD: Cβnls
CfaAffx,17 familisris similar to πucteotiπ-relβted protein; 297,1, S1 S transcript variant 4 XM 8565 at 8.42E-03 2.14E-02 0.67 (LOC60S44S); mRNA 20 NCL nucleolin fβmiliaris similar to nuctear receptor nucl reactivator I isoform 2; ear
Cfa.9642.1 transcript variant 3 XM 8534 receptor
,A1 S at i.4Se-02 2.71E-O2 0,74 (LOC475684), mRNA 39 NCOA 1 coactjvator 1 famtliaris similar to
CfaAffx.27 I nuclear receptor co- nucl reprisssof 1; transcript ear 681.1.S1 ai variant 5 (LOC47S515); XM 8586 receptor co- t 6.SJE-03 1.966-02 0.74 mRNA 80 NCOR1 repressor 1
NDC80 homolofl, kinetochore
PR6D1CTED-. Canls faniiliaris similar to complex
Cfe.3066.1 kinetochore βssocatec 2 XM 5373 component .81 at 2.46E-02 3.47E-02 0.76 (LOC480190); mRMΛ 13 NDC80 (S. cerevisiae)
PREDICTED: Canis ftimiliβris similar to N«M4 Nedd4 family
Cfe.865.1, family interacting protein XM 5341 interacting S1 at 2.39E-02 3.42E-02 075 2 (U3C476956); mRNA 56 NDFIP2 protein 2
PREDICTED: Cams NADH familiaris similar to NADH dehvdroqenas dehydrogenase e (ubiquinone) (ubiquinone) 1 alpha 1 alpha subcomplex; 10; 42kDa
Cfe.10289. PiBCU)1SOi (LOC608244); XM 8452 NDUFA subcomplex.
1.S1 at 4.24E-03 1.68E-02 073 ΓΛRNA 10 10 10. 42KPa
NADH
PREDICTED. Cams familiaris similar to NADH dehvdroαenas dehydrogenase e (ubiquinone)
CfaAffx,19 (ubiquinone) 1 alpha 1 alpha subcomplex; 10; 42kDa 535.1.51 S piecu^ot (LOC6Q8244); XM 8452 NDUFA subcomplex. at 4.09E-CW 9.6SE-03 072 mRNA 10 10 10. 42kPa
NADH dehvdroQβnas
PREDICTED: Cams e (ubiquinone) familiaris similar to t3kDa 1 alpha differentιatιon-as5cda«iJ
Cfa.4375,1 protein (U0C475428); XM 5326 NDUFA subcomplex.
.51 a at 9.78E-(W 1.J6E-02 076 r«RNA 52 12 12
2)4 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Canis famsliaris similar to NAOH ubiquinone αxidβreductβs* 616.6 suiκmft (Complex J- 816.6) (σ-BJ6.6) (Gene associated with retinoic- NADH lnterferon-lnduce<J dehvdroαenas mortality i9 protein) e (ubiquinone) (GR1M-19) (CeIi deatr- t-egutator/ protein GfifM- 1 alpha
Cfe.18026. 19); transcript variant 1 XM 5338 NPUFA subcompiex. 1.S1 S at i.StE-CH 9.00E-03 0.65 (LOC476659), mRNA 13 13
NADH
PREDICTED. Cams dehvdroαenas famlllarts similar to NADH e (ubiquinone)
CfaAfix,97 dehydrogenase 1 alpha (ubiquinone) 1 alpha
46.1.S1 s subcompiex; 2: SkOa XM 5352 subcompiex. at 4,09E-M 9.68E-03 0.71; (LOC478032); mRNA 11 2. 8kDa
NADH
PREDICTED: Cante famillaris similar to NADM- dehvdroαenas ubiquinone e (ubiquinone) oxi(Jored«ctas« MUtQ 1 aloha subuπtt (Comptex 1-
Cfa.4415.1 MLRQ) (Cl-MLRQ) XM 5348 subcompiex,
,S1 at 1.36E-(M 8,90E-03 076 (LOC477632); mRNA 77 4, 9kDa
PREDICTED: Cante NADH familiaris similar to NAOH dehvdrooenas ubiquinone e (ubiquinone) αaAffx,42 oxidort*d«ctase MLSQ 1 alpha subursit (Comptex 1« 75.1.S1 s MLRQ) (Ct-MLRQ) XM 5348 NDUFA subcompiex.
1.096-03 1.20E-O2 0.69 (LOC477632); mRNA 77 4 4. 9kPa
NAPH
PREDlCTED: Canls familiaris similar to NAOH dehvdrogenas ubiquinone e (ubiquinone) oxidoreductase MUtQ 1 aloha subursit (Comptex 1«
CfiaAfftc.76 MLRQ) (CI-MLRQ) XM 5348 NDUFA subcompiex, 4.1. S1 at 6.8ie-02 6.06E-O- 1.33 (LOC477682); mRNA 77 4 4. 9kDa
NAPH
PREDICTED: Cams dehvdrogenas familiaris similar to NADH e (ubiquinone) dehydrogenase 1 aloha (ubiquinone) 1 alpha
Cfa.11777, ϋubcompiex; 6; WkDa XM 5317 NDUFA subcompiex.
1.31 at 4.676-05 7.75E-O3 1.33 (100474*83); mRNA 12 6 6, 14kDa
NAPH
PREDICTED: Cams dehvdrogenas familiaris similar to NAOH e (ubiquinone) dehydrogenase 1 alpha (ubiquinone) 1 alpha
Cfa.11777, 5Ubtornpie>; 6; 1IkDa XM 5317 NDUFA subcompiex.
2.A1 s at 2.05€-05 7.55E-O3 0.66 (IOC474383); mRNA 12 6 6. 14kDa
2J5 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000217_0001
2J6 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
NADH
PREDICTED: Cams dehvdrogenas fβmillarts similar to NADH e (ubiquinone) dehydrogenase 1 beta (ubiquinone) 1 beta
Cfe.10947. subcortex; 9; 22kDa XM 5323 subcomplex,
1.81 at 4.86C-03 1.7SE-O2 0.76 (LOC475094); mRNA 26 9. 22kDa
NADH dehvdroQβnas
PREDICTED: Cams e (ubiquinone) fβmillarts similar to NADH Fe-S protein dehydrogenase 1. 7SkDa (ubiquinone) Fe-S protein 1; 7SkDa precursor, (NADH-
Cfe.17764. transcript variant 7 XM 8S46 NDUFS coenzyme Q
1.81 s at 4.13E-03 i.eeε-o∑ 0.76 ILOC470330); mRMA 04 1 reductase)
PREDICTED: Cams NADH famiiisris similar to NADH' dehvdroαenas ubiquinone oxtdoϋeductass 18 kDa e (ubiquinone) subunlt; mltoeSiondriBl Fe-S protein precursor (Complex MS 4. JδkPa kθ«) (CM8 kθa) (NAPH- (Compϊex J-AQOQ) (Q-
Oa.9529.1 AQOQ) (LOC479335); XM 5364 NDUFS coenzvmβ Q
■A1 s at 2.26E-03 1.38E-02 0.67 rnBNA 74 reductase)
PREDICTED: Cams NADH familidris ainilsi to NADM dehvdrogenas ubiquinone oxtøoredwetase IS kDa e (ubiquinone) subunlt; mitocnondrfsl Fe-S protein precursor (Comptex M8 4, 18kDa
CfaAffx.15 kDa) (CI-18 kθa) (NADH- (Compiex I-AQDQ) (Q- 952.1.S1 s AQOQ) (LOC479335); XM 5364 NDUFS coenzvme Q at 9,10£-(M l.lSE-02 0.67 mRNA 74 4 reductase)
NADH dehvdrogenas
PREDICTED: Cams e (ubiquinone) farmliaris simitar to NAOH Fe-S protein dehydrogenase 6, 13kDa (ubiquinone) Fe-S protein (NADH- 6; BXDe (NADH-
Cfa.4245.1 coenzyme Q reductase) XM 5358 NDUFS coenzvme Q
.S1 s at 3.88E-0S 7.SS6-03 0.67 (LOC478δ29), mRMA 02 6 reductase)
PREDICTED; Canls NADH familiariδ similar to NADH dehvdrogenas
CfaAfix,28 I dehydrogenase (ubiquinone) flavoprotein e (ubiquinone) 547.1, S1 al 2; 24kDa (LOC480204); XM 5373 flavoprotein 2. t i.876-03 X.32E-O2 0.7S mRNA 28 24kDa
2J7 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
neura)..
PREDICTED-. Cants precursor cell familieris similar to neυrai expressed, precursor cell expressed; developmefrtally down- developmental
Cfa.734.1. regulβted gene S XM 5373 Iy down-
A1 s at 2.S9C-04 9.236-03 O.SS (LOC480265); mftNA N£DD8 regulated 8
Bos taurus neuroepithelial cell transforming gene i; neuroepithelial mRNA (cONA clone c MGC: 127767 ell
Cfe.16364. IMAG£:?956312); transforming
S.04ε-04 1.106-02 0.4S complete ods BC 102658 NET1 qene 1
PREDICTED: equus nuclear factor cabalius nυd&ar factor of of activat activated T-cells S; ed T-
Cfa.19790. tontcfty-.tisporislve XM 0014 cells 5. tonicity
1.81 at 6.17E-03 1.93E-02 0.75 (NFAT5); mSNA 97295 NFAT5 responsive
PREDICTED. Cams fβmlllarts similar to nuclear factor
CfaAffx,31 nuctear factor of actjvatatf of activat T-celts 5 isoforrn b; ed T 027.1.S1 S transcnpt variant 1 XM 5468 cells 5. tonicity at 2.2SE-02 3.32E-02 0.7S (LOC489734); r»tRNA 54 NFAT5 responsive
PREDICTED-. Osπls faniiliaris similβr to neuropuidin.
Oa.2119.1 Prot«n α*)rfl20 XM 5477 EIF4E binding
■S1 s at 8.43E-(M 1.12E-02 0.73 α<X490612); mRMA 34 NGDN protein ninein
CfaAffx.22 Homo sapierss mnein (GSK3B (GSK36 ifttβfsctmg 448.1.S1 S protein) (NIN): transcript NM 0209 interacting at I.93E-02 3.10E-02 0.7-f variant 2; mRNA 21 NIN protein) famillarts similar to 6CS ribosome subunit biogenesis protein NIP7 nucl homotog (KD93); ear import
Cfa.466.2. transcript variant 2 XM 5368 7 homoloα (S. S1 a at 8.S8E-03 2.196-02 0.76 (LOC479673); mRMA 04 NIP7 cerevisiae)
PREDICTED. Cams famillarts similar to oen non imprinted
CfaAfix.15 imprinted in Pradar- in Prader- Wiili/Angeiman syndrome 288.1.51 s Z isotorm a (IOC479002); XM 5361 Willi/Angelma at 3.81E-M 9.6tE-03 0.74 mRNA 57 NIPA2 n syndrome 2 non- metastatic
CfiaAfftc.26 c
Canis lupus familiaris ells 1 , orotein 479.1.31 x nm23-Cl mRNA for NM23- (NM23A) at ..72E-03 1.3OE-O2 0.71! Ct; complete cds AB207044 NMEl expressed in non- metastatic c
Su5 scrofa mRNA for c- ells 2. protein
Cfa.S618.2 myc transcription factor; (NM23B)
.S1 s at 3.376-05 7.S5E-O3 0.73 complete cds AB292B46 NME2 expressed in Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000220_0001
2J9 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000221_0001
220 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
O-linKed N- acetyloiucosa mine
(GIcNAc) transferase
(UDP-N- acetviqlucosa
PREOlCTED. Cams mine:polypepti fβmiliaris similar to O- de-N- linked GtcNAc transferase ac Boform X; transcript etviglucosa
Cfa.15244. variant I (LOC4809SS): XM 5380 minyl
1.81 at i.696-02 3.06E-O2 0.76 mRNA 75 OGT transferase)
O-linKed N- acetyiqlucosa mine
(GIcNAc) transferase
(UDP-N- acelylgiucosa
PREDICTED: Cams mine:polγpepli famιliari5 similar to O de-N- linked GIcNAc transferase ac lsofotrn 1; transcript etylgiucosa
Cfa.874.2. variant 1 (LOC480SSS); XM 5380 minyl S1 s at 2.78E-03 1.48E-02 072 mRNA 75 OGT transferase)
O-liπked N- acetviαlucosa mine
(GIcNAc) transferase
(UDF-N- acetvigiucosa
PREDICTED: Canis mine.polvpepti fβimiliaris similar to O de-N- lir.ked QIcNAc transferase ac isoform 1; transcript etviqiucosa
Cfa.18574. variant 3 (LOC480955); XM 8534 minyl
1.S1 s at I.80E-03 1.306-02 0.69 mRNA 69 OGT transferase)
O-linked N- acetylglucosa mine
(GIcNAc) transferase
(UDF-N- acetylQiucosa
PREDICTED: Cams mine:polypepti famillaris similar to O- de-N- lirkad GItNAc tvansfersse isoforrn 1; transcript acetviqiucosa
Cfa.2Q643, variant 8 (LOC480955); XM 8537
1.S1 s at 5.SiE-(M 1.O2E-O2 07 mRNA 15 OGT transferase) faniiliβris similar to Putatwe GTP-txnding protesπ PTD004; αa.19273. transαipt vβrtant 2 XM 8452 Obp-like
1.S1 at S.34E-04 1.166-02 f (LOC47SS03); mRNA 27 OLA1 ATPase 1 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PKEDICTcD; CaniS farnHlarts similar to opfec Qgtic.atrophy.
Cfa.1129,1 atrophy 1 isofomi 8 XM 5343 1 (autosomal
4.4S6-03 1.70E-O2 0.76 (IOC477129); mRNA
PKtDiCTtD: tanTs 21 OPA 1 dominant) optic atrophy famιliari5 similsr to σj&c
Cfa.1129.1 rtrophy 1 eσfσrm 8 XM 5343 1 (autosomal .S1 s at 3.966-02 4.486-02 6 (LOC477129); mftNA 21 OPA1 dominant)
CfaAffx.12 i FKeDiCTcurcanis familiaris olfactory ■ 1.S1 ai receptor (ORCMAOi); XM 5406 OR04A0 olfactory t 4,146-04 9.686-03 1.411 mRNA 54 1 receptor oriQin
PREDICTED: Cams recognition farroliaris similar to orςin co recognition complex mplex,
Cfe.20932. Subunit 4 (LOC476141); XM 5333 subunit 4-IiKe
1.S1 s at i..7ε-(M 8.90E-03 0.7 mRNA 48 ORC4L (yeast) origin
PREDICTED. Cams recognition familiaris similar to of , gin complex, recognition complex
CfaAffx,92 subunit 4 (LOC476141); XM 5333 subunit 4-like 39.1.S1 at 1.53E-03 1.26E-02 0.71: mRNA 48 ORC4L (yeast) farmliarts similar to oxysteroi-bindiπg protein- oxysterol like protein 11; traosctipt
Cfa.1563.1 variant 2 (LOC478S96); XM 8440 OSBPL1 binding
,S1 at I.6SE-03 l.286-0a 0.75 mRNA 91 1 protein-like 11 famiiiβris similar to oxyβtero! binding protein- oxysterol like 9 isσfefm b;
Cfa.1061.2 transσipt vβrtβnt 5 XM 8543 bindinp,
.A1 a at 2.10E-02 3.22E-02 0.76 (LOC47S3SS); mRMA 94 OSBPL9 protein-liKe 9 sialoolvcoprot
CfaAfftt,14 I
Homo sapiens mRNA for ein 794.1.S1 ai putative endopeptidas t i 3.14E-03 1.S36-O2 0.7S siaioglycopfxtfease type 2 AJ295148 L1 e-like 1
3-oxoacid
Felis catus 3-oxθ3Cid CoA
Cfa.10153. trsnsfarβse 1 (OXCTl) CoA 1.S1 at 2.38E-03 1.40E-02 0.69 mRNA; partial cds EU650370 OXCTI transferase 1
PREDICTED: Cams 3-oxoacid famϋiaris similar to 3-
Cfe.16630. oxoacid CoA transferase 5 XM 5364 CoA
1.S1 at 5..6E-02 S.30E-02 0.7S (LOC479347); mRNA 87 QXCJI transferase 1
CfaAffx,28 PREDiαED: Canis 3-oxoacid familiaris similar to 3- 412.1. S1 s oxoacid CoA transfet»se 5 XM 5364 CoA at l.SOE-02 2,7SE»02 0.77 (LOC479347); mRNA 87 OXCT1 transferase 1
PREDICTED: Cams poiy(A) familiaris similar to binding
CfeAfix.26 polγ{A) binding protein prot Iπtβrseting protein i; ein 373.1.S1 s transcfipt variant J XM 5364 interacting at i.726-02 2.93E-O2 0.77 (LOC479343); mRNA 82 PA1P1 protein 1
OaAffx.15 I PRfOICTFD. Cams PAK 1 fβmillarts similar to PAKl 220.1. S1 ai interacting protein J XM 5358 PAK 1 IP interacting t i s.4sε-oa 5.36E-O2 0.74 (LOC4787.9); mRNA 84 1 protein 1
222 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PAN3 polyA
PREDICTED-. Cants specific famiiiβris similar to PABPl ribonucleasβ
CfiaAfftc.11 I dependent poly A-specf-c riboπuctesse sufκinit 016.1. S1 al PAN3 (LOC486024); XM 5431 homolog (S. t ..oβε-oa 2.35E-O2 7<! rnftNA 50 PAN3 cerevisiae)
CfaAffx.26 PREDICTED: Pan troglodytes hypothetical
074.1, S 1 ai LOC462250 XM 5180 pantothenate I I 7.766-03 2.066-02 0.65 (100)62250); mftNA 8? PANK3 kinase 3 farroliaris similar to
Cfa.19159. pantothenate kinase <t XM 5367 pantothenate 1.A1 at i.neoz 2.42E-02 0,74 {LOC479579); mRNA 18 PANK4 kinase 4 famtliaris similar to PAP PAP
CfaAffx.14 associated domain associat containing 4; transcript ed 274.1.S1 s variant 2 (LOC607764); XM 8446 domain at 2.11E-03 1.38E-02 0.68 mRNA 05 FAFD4 containing 4
CfaAffr,27 I PREDICTED'. CAΠIS faniiliaris similβr to POlV(A) 222.1.S1 ai poly(A) polymerase a^ha XM 5375 polymerase t ! 19SE-03 1.33E-O2 0.75 (LOC480430), mRMA 51 alpha
Parkinson disease
CfaAffx,30 PREDICTED: Canis (autoso farmliaris similar to 03-1 mal 082.1.51 S protein: transcript vβfiβnt XM 8539 recessive, at 1. OSE-CM 8,90E-03 0.7116 (LOC479S9S); mRNA 38 PARK7 early onset) 7 fanύliβris similar to
CfaAffx.1B present In 3S5ociated; presenilin rhomiwici-rike; transcπpt 810.1.31 s variant Z (LOC488100); XM 5452 associated, at B OSE-03 2.106-02 0.77 mftNA 24 PARL rhomboid-like ρterin-4 alpha- carbinolamine dehydratase/'d imerization
PREDICTED. Cams cofactor of fβmiilarts similar to hepatocyte tJimefization cofactor of nucl hepatocyte mjtl«ar factor ear factor
CfeAffx.24 i (HNf=I) from mu&de XM 8473 1 aloha 76.1.S1 at i.49E-0S 7.SSE-O3 0.76 (LOC609970); mRhU 32 PCBD2 (TCFD 2 pterin-4 alpha- carbinolamine dehvdratase/d imerization
PREDICTED: Cams cofactor of familiariδ similar to hepatocyte
CfaAffx.24 dimewation cofastoi of nucl hq»tocyte mictear factor ear factor 76.1.51 s 1 {HNP1} from muscle XM 8473 at 2.σsε-03 1,3SE-Oi 0.77 (LOC60W70); mRNA 32 PCBD2 (TCFD 2
223 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
farmliaris similar to Pf.QPion.yl. propionyl-Coefi_yme A Coenzyme A carboxylase; alpha carboxylase. polypeptide precursor;
CfaAfftc.97 transcnpt variant 2 XM 5341 alpha 32.1.S1 at 3.saε-03 1.S9E-02 0.72 (LOC476975); mRNA 75 PCCA polypeptide
PREDICTED: Canis familiaris similar to Proplenyi-CoA carboxylase beta chain; mitochondrial precursor (PCCase beta sutκmit; propionv) (Propar»oyi-CoA:carbon Coenzyme A
CfaAI8c.11 dtoxide lipase tela carboxylas suburit); transcript e,
739.1.S1 S variant 3 (LOC477076); XM 8596 beta at 1.S7E-03 1.2SE-O2 0.77 mfWA 11 PCCB polypeptide
PREDItTTeD.' QIJIiS famillaris similar to Protesn-L -lsoBspatt8te( D- sspartate) 0- methylcransferase (Proteiπ-beta-Λsμβitste nvethyltransf erase) (PIMT) (Protein L- isoβspartγl/D-aspa»tyl Pfotein-L- methyltcaiisferase) (L- isoaspartate soaspirtyl protein (D-aspartate) carooxvl methyltransf erase);
CfeAflx,15 transαipt variant 9 XM 8567 methyltransfer 50,1 -S1 at S.(ME-03 1.77E-02 1.74 (LOC476242); mRNA 39 PCMII ase
PRtDIcTtDTCaRiS familiaris similar to Prot«sn-l-isoaspartatfi(D- aspartate) 0- rrtethyltransf erase (Proteiπ-beta-βspβrtate nwthyfaansferase) (PU-IT) (Protein L- isoaspartyi/ϋ-aspartyl protein-l- methyttraπsferase) (L- isoaspartate Isoaspartvl protein (D-aspartate) carisoxyl mettsyltrar*fer3se); Qz
Cfa.3996,1 transαipt variant 10 XM 8567 methyltransfer
,A1 s at 1.0iE-03 l,t7E-02 I.7S (LOC476242); niRNA 69 PCMII ase famillarts similar to prolif proliferating cell nuclear erating
Cfa.525.1, antigen (LOC477166). XM 5343 cell nuclear S1 at 3.67E-03 1.61E-02 0,67 mRNA 55 PCNA antigen
PEST proteolytic
PREDICTED: Canis signal fatiύliaris similar to PEST' containing nuclear protein containing
Cfe.14096. (PCNP); transcript variant XM 5357 nuclear 1.S1 at 7.46E-03 2.03E-02 0.76J1 (LOC478546); mRNft 23 PCNP protein
PEST proteolytic
PREDICTED: Cams siαna) familiaris similar to PEST- containing nucfear protein containing
Cfa.14096. (PCNP); trsnscrtpt variant XM 5357 nuclear 2.S1 $ at I.S3E-04 9.0OE-O3 OJIi 1 (LOC47SS46); mRNA 23 PCNP protein
224 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000226_0001
225 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
fsmillarts similar to Protein (Jisuiffsse- protein tsomerase A4 precursor disulfide (Protein ERp-72) isomerase t£Rp72); transcript
Cfa-4275,2 variant 1 (100)82715); XM 5398 family A,
-S1 at ..soε-03 1.25E-O2 mRNA 31 PD1A4 member 4 famiiiβris similar to Protest) disulfκte- protein isorwrase A4 precursor disulfide
CfeAffx.60 (Protein ERp- 72) iso (ERp72); transcript merase 54.1.81 s vartant 3 (LOOHWnS),' XM 8431 family A.
M. 2.44€-03 1.41E-02 0.7 mSMA member 4
PREDION. Cams fβmiliails similar to protein Protein disuificSe- disulfide tsomaras« A6 precursor iso (Thioredσxin ctomain merase
Cfe.20623. containing protein 7) XM 5328 family A, 1.81 s at I.47E-03 1.2SE-02 0.7 (LOC475668); mRNA 76 PDIA6 member 6
PREDiαED: Canis farwlians similar to roteir Protein rtisuifioe- disulfide
CfaAffx.61 tsomefβsa A6 precursor iso (Thioredcxm ctomairt merase 63.1.S1 S containing piotein 7) XM 5326 family A, at 2.S2E-03 1.43E-02 0.71; (LOC475668); mRNA 76 PDIA6 member 6
PREDICTED: Canls familiaris similar to [Pyruvate dehydrogenase [iipoβmkJe]] kirase Isozyme S; mitochondria! pyruvate
CfaAfix.20 I precursor (Pyruvate d dehydrogenase kinase ehvdrogenas 244.1.S1 al isσform 1) (LOC476S28)j XM 5340 e kinase, t ! 5.18E-0S 7.92E-03 072 mRNA 32 PDK1 isozyme 1
CfaAffx,25 i PREDICTED: Canis familiaris similar to POZ 687.1.51 ai domain containing 11 XM 5490 PDZ domain t ! 9.saε-03 2.2SE-O2 0.73 (LOC491940); mRNA 60 PDZD11 containing 11
CfaAffx,18 i PREDICTED: CaniS famiiiaris similar to POZ 596.1. S1 ai domain containing 8 XM 5440 PDZ domain t ! 1.70E-02 2,91E-02 0.72 (LOC4S6909); mRNA 39 PDZD8 containing 8
CfeAffx,56 CKtuititu.' wπis famlllarts similar to peilino peiiino 99.1.S1 s protein (LOC4S138S); XM 5385 homoloα, 1 at I.33E-03 1.23E-02 0.69 mRNA 08 PELH (Drosophila)
PREDICTED. Cams familiaris similar to Peroxisomal biogenesis factor 3 (PecoxfivS) p (Peroxisomal assembly eroxisomal
CfeiAfϊx.14 protein P£X3) XM 5411 biogenesis 04,1 -S1 at 1.52E-03 1,2SE»O2 0.72 (LOC48401S); mRNA 32 PEX3 factor 3
"KTTΪΠUTΪTWΓ famiiisris similar to
Cfa-17565. pnβfotoin 2 (LOC468648); XM 5457 prefoldin 1.81 s at I.S9E-03 1.26E-02 0.75 mRNA 85 PFDN2 subunit 2
226 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000228_0001
227 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Carts famiHaiis similar to phosphoinositi pnosjjhoinosmde-3- de-3-kinase, Mnase; regulatory subunit
Cfa.8254.1 4; pl50; transcript variant XM 5342 repuiatory -A1 at 3.68£-02 4.30E-02 0.73 1 (LOC477064); mRNA 60 P1K3R4 subunit 4
PREDICTED: tans familiaris similar to pigeon
CfaAffx.73 CG10739-PA XM 5331 homoloq 75.1.S1 at 4.47E-03 170E-02 0.73 (IOO57S903); mRNA 10 PION (Drosophila) pifi.n .O.ron- binding
PRCDICTCD: Canis
Cfa.871.1, famϋiaris similar to Pirin XM 5379 Sl at 8.496-02 6.S8E-O- 0.76 (LOC480846); r»tRNA 63 PIR protein) famtliaris similar to Phosphatidyiinosito) transfer protein beta isoform (Ptdins transfer protesπ beta) (PtdEnsTP) (PJ-TP-Ma); transcript pliosphatidvϋn
Cfa.20719. variant 2 (LOC609712); XM 8596 ositol transfer
LSI s at 2.89£-03 1.49E-02 0.77 mRNA PITPNB protein, beta famlllarls similar to praja
CfaAffx,12 2; RJNG-H2 motif Praia 2. RING- containing; transcript 014.1.S1 s vβfiβfrt 2 (LOC473143); XM 8507 H2 motif at i.siε-02 2.7SE-02 0.72 ΓΛRNA 32 PJA2 containing
PREDICTED: Canis farmliarts similar to prostate Transmembrane prostate transmembran androgen- lndttced protdn (Soild tumor-associated 1 e protein,
Cfe.14230. protein) (LOC48S94S); XM 5430 PMEPA androgen
5.72E-04 1.036-02 0.7 mRNA ZS 1 induced 1
PREDICTED. Cams fβmiliails similar to Mitochondria! processing peptidase peptidase beta subumt; ( mitochondrial precursor mitochondrial
Cfe.290.1. (δeta-MPP) (P-52) XM 5331 processing) A1 at 2.96E-03 l.StE-02 074 (LOC475897); mRhU 04 PMPCB beta
PREDICTED: Canis PMS 1 fβimiliaris similar to PMSl postmeiotic
CfaAfftc.14 protein ftomoiog 1 (ONA segregation mismatch repair protβm 811.1.S1 S PMSl); transcf pt variant XM 8505 increased 1
2-99C-03 1.S1E-02 0.7^2 (LOC47S840); mRNA 87 PMS1 (S. cerevisiae) pinin.
CfeAfix.21 Canis lupus famillaris d pinin; desmosome esmosome 428,1.81 s sssoclatsa protein (PNN); NM 0010 associated at 2.366-02 3.40E-O2 0.7S mRNA 03231 PNN protein polymerase
PREDICTED: Cams (DNA- familisris sirnilsr to DfW dir polymerase epsilon ected),
Cfa.9261.1 subunit 4 (IOC4S3096); XM 5402 epsilon 4 (p 12
,S1 at 7,%E-CJ4 1.10E-02 OJS mRNA 12 POLE4 subunit)
228 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000230_0001
229 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PRK)ICTgD: Cβnls
CfaAffx,13 familisris similar to p peptidytptχ>iyl isomerase eptidylprolyl 745,1, S1 S 0; t?af-script variant i XM 5327 isomerase D at Ϊ.3SE-04 3.90E-03 0.7 (LO047548-); mRNA 04 PPfD (cvclophilin D)
PREDICTED: Cams farroliaπs similar to Peptidyl-prolyi cis-traπs isorntrasβ; mitochondrial precursor (PPlase) peptidylprolyl
Cfa.16705. (Rot9rrv3se) (Cydopfnlm XM 8480 isomerase F 1, SJ9E-04 1Λ2E-02 0.76 F) {IOG610502); mfWA 21 PPfF (cvclophilin F)
PREDICTED: GmIs
CfaAHx.46 familiaris similar to p peptidyl prolyl isomerase eptidylprolyl 85.1.S1 s H; transcript variant £ XM 8431 isomerase H at 3.24C-03 1.55E-O2 0.76 (LOC606S9S); mRNA 44 PPfH (cvclophilin H) protein phosphatase
CfaAffx,19 Homo 5aps«ris protein 1. r phosphatase .; regulatory egulatory 929.1.S1 S subunit 7 mRNA, (inhibitor) at 7.02E-03 1.99E-02 '6 complete cds BT020134 PPP1R7 subunit 7 protein phosphatase 2 (formerly
Canis famllaris type 2A 2A). catalytic protein phosphatase
Cfa.1403.1 catalytic subuπΛ mRNA; subunit. alpha
,S1 s at i.ise-03 1.2JE-O2 0,76 complete α)s AF448499 PPP2CA isoform protein
PREDICTED: Cams phosphatase famιlιan5 similar to beta 2 (formerly isofoim of retjulatotγ 2A), subunit A; protein phosphatase 2 isofom b; repuiatorv
Cfa.8744.1 transαipt vanant J XM 5365 PPP2R1 subunit A.
■A1 s at i.sie-oi 1.25E-O2 0.67 (LOC479ΛΛ4); mRNA 79 B beta isoform protein
PREDICTED: Canls phosphatase famiiiβris similar to beta 2 (formerly isoform of regulatory 2A), subunit A; protein r phosphatase 2 isoform b; egulatory
Cfa.6744.2 transcript vβriβnt 8 XM 8574 PPP2R1 subunit A,
■S1 at S.846-04 1.03E-O2 0.76 {(.0O17S444); mRNA 35 I beta isoform protein
PREDICTED: Csnls phosphatase familisris similar to alpha 2 (formerly isoform of regulatory 2A), subunit 855; protein phosphatase 2; transcript regulatory
Cfa.i 163.1 variant S (LOC477374); XM 8533 PPP2R2 subunit B, ,Al s at 4.39E-04 9,78E-OJ 0.76 mRNA 04 alpha isoform famHiaris similar to peptidylprolyl peptidylproiyl Isomerase isomerase dortwm and WD repeat domain and containing t; tfanscriot
Cfa.10581, variant 1 (IOC478078); XM 5352 WD repeat 1.S1 s at t.tm-oz 2.386-02 0.S6 mRNA 56 PPWD 1 containing 1
230 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famsiiaris stmilar to
Cfa.4507,1 peroxiredoxin 1 XM 5325 peroxiredoxin
.A1 at 3.426-03 1.57E-O2 0.7<? (IOC475375); mRNA 99 PRDX 1 1
CfaAffx.78 FKeDiCTcurcanis familiaris similar to 06.1.S1 s peroxifedoxin l XM 5325 pβroxjredoxin..
M 6,08E-(M i.ioε-oa 0.7 (UXT475375); mRNA 99 PRDX1 1
PRtWCI1ED: Cams familiaris similar to Peroxiredoxin 6 (Antioxidant protein 2) (1- Cys peroxlrettoxin) (l-Cys PRX) (Acidic caWum- irκjeμeficient phospholipase A2) (a!PU2) {Non-sβJeniun glutathione perαxi&stf) (MSG^x) (24 kOa protein) (Uver 2D page spot 40)
Cfa.3121.4 (Red blood cells page... XM 5371 peroxiredoxin
-S1 at 3.516-02 4.20E-O2 0.76 (LOC4S0069); mRNA
PREDICTED: Cams famtliaris similar to (M 9- like protptn (25 kOβ protein of reievarrt evolutionary and lymphoid interest)
Cfa.12159. (PREU); transcript vwiant XM 5364 PRELi domain
1.A1 at 7,S9€-03 2.046-02 0.7^1 (LOC479276); mRNA 19 containing 1 familiaris similar to
CfaAffr.10 Protesn Wnas« C; ou type (nPKC-nu) (Protein kinase 207-1.S1 S EPK2) (I.OC483036); XM 5401 protein kinase at 9.84C-03 2.29E-02 0,75 mRNA 51 PRKD3 D3
PREDICTED: Canis
CfaAffx.15 fcmillarls similar to HMTl arqinin hnRNP methyitransferase- e 427.1.S1 s like 3; transcript variant 1 XM 5340 methyltransfer
£L 7.93E-04 1.106-02 0.68JtLQC476887); mRMA PRMT3 ase 3
PRP39 pre-
PREDICTED: Cams mRNA famiiisris similar to PRP39 processing pnβ-mRiNA processtng factor 39 homokxj; factor 39
Cfa.2377.1 transcript variant l XM 5374 homolog (S.
.S1 at ..isε-02 2.47E-O2 0.73 (UXHSO3O5); mRNA 27 PRPF39 cerevisiae)
PRP4 pre- mRNA
PREDICTED: Cams processing αaAffx,57 famiϋarls similar to PRP4 factor 4 pre-mRNA procassing S0.1.S1 S factor 4 homolog XM 5320 homoloq at UOE-(M 9.00E-03 0.72 (LOC474S07); mRNA 38 PRPF4 (yeast)
PREDICTED; Osnls familiaris similar to Fortnlf binding protein 2 PRP40 pr (Hurrtingtin yeast partner e- A) (MurttlngtSivSnteracting mRNA protein KVWFSPIl) (Pa. processinp ligand associated factor 1 (NY-REN-6 antigen): factor 40
Cfa.3344.1 transcript variant 1 XM 5333 PRPF40 hornoloq A (S,
,S1 at 4.StE-(M 9.SSE-03 0.64 (LOC476I52), mRl^A 59 cerevisiae) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000233_0001
232 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Canis Pfoteasornβ. famtHaiis similar to (prosome. proteasome alpha 3 macropain) subunit isoform 2;
Cfa.4336.1 transcript vsrisnt 1 XM 5374 subunit. alpha
-S1 s at S.S3E-(W 1.O3E-O2 0.69 (LOC480338); mRNA 60 PSMA3 type, 3
PREDICTED: Cams familiaris similar to Prøteasom* subunit alpha type 4 (Proteasome component C9) (Macropain subunit C9) proteasome (Mυtticatalytic (prosome, endopeptldase complex suburit C9) (Proteasome macropain)
Oa.10406. subunit L) (LOC475132); XM 5323 subunit, alpha
1.S1 at 5.71E-03 1.S4E-02 O 67 mRNA 62 PSMA4 type. 4
PREDICTED. Caπls famiiieris similar to Proteasom* subunit alpha type 4 (Proteasome component C9) (Macropalfi subunit C9) proteasome (MυlticataJytic (prosome,
CfaAffx.35 enc)op«ptictase eompl«< subunit C9) (Pixsteasome macropain) 22.1.S1 s subunit L) (I.OC475132); XM 5323 subunit. alpha at 7,49£-03 2.036-02 0.72 mRNA 62 PSMA4 type. 4
PREDICTED: Cams familiaris similar to Pιt*easom« subunit alpha type 5 (Proteasome jeta chain) (Macropain seta proteasome chain) (Multicatalytic (prosome, endopeptϊΛsse complex macropain) «eta chain); transcript
Cfa.12672. variant 2 (LOC490123): XM 8609 subunit. alpha
1.A1 s at 6.93E 03 1.98E-02 0,77 mRNA 92 PSMA5 type, 5
PREDICTED. Cams familiaris similar to Proteasome subunit alpha type S {PfoCeasomβ zβta cJiβln) (Mdcjopam zeUt proteasome chain) {Multtcatalytic (prosome, endopeptidase complex zeta chain); trsrtscrip* maαopain) αa.9709.1 variant 2 (LOC490123); XM 8609 subunit, alpha
.S1 s at ..42E-03 1.25E-O2 0.75 mRNA 92 PSMA5 type. 5
PREDICTED: Canls famiiisiis similar to Proteasome subunit slpha type 6 (Prcfteason've iota ctsain) (Maαopaln lota proteasome chain) (Mυlticatalytic (prosome. widop«ptkia«e complex iota chain); transcript macropain)
Cfa.S494.1 varβnt 2 (LOW80290); XM S374 subunit. alpha
■S1 s at 3.21E-05 7.SSE-03 0.7 mRNA 12 PSMA6 type. 6 proteasome (prosome.
PREDICTED: Cams familiaris TATA-box macropain)
CfaAffx.70 birxSing pfotelrt XM 5322 subunit, beta 79.1.51 at 7.93E-06 6.68E-03 0.7J; αθC475040); mRMA 75 PSMB 1 type. 1
233 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
farrnllaris similar to Proteasome subunit beta type 4 precursor (Pcoteasom* bda chain) (Macropairi beta chain) proteasome (MulticatølytK (prosome, endopeptkiasβ complex beta chain) (Proteasome macropain)
Cfa.4329.1 chain 3) (UX47SS-1S;, XM 5330 subunit. beta
,S1 s at 2.596-03 1.44E-O2 0.76 mSMA 57 PSMB4
PREDICTED: CartiS famtliaris similar to Proteasome subunit beta type 6 precursor tPfoteasαm* delta chain) (Macropain delta chair-) proteasome (Multicafcdytic (prosome, endopeptϊΛsse complex tJeHta chain) (?>rcteascme macropain)
Cfa.2648.1 5uburit Y) {LOC60?466); XM 8441 subunit. beta ,S1 s at 4.63E-CW 9.SSE-03 0.69 mSNA 48 PSMS6 type. 6 familiariδ similar to proteasome peptidase {prosome; (prosome,
CfeAffx.26 I maciopaln) 26S stiburtlt: ATPβse 1; transcript macropain) 768.1 -S1 al variant 2 (lOO» 78703); XM 8434 26S subunit. t i 5.686-02 5.46E-02 0.76 mSMA 31 PSMC 1 ATPase, 1
PREDICTED-. Osπls proteasome familiaris similar to (prosome, proteasome (prosofrw; macropain) 26S subunit; maαopain)
Cfa.281.1, ATPase 2 (LOC475896); XM 5331 26S subunit, S1 s at 3.83E-04 9.61E-03 OJIi mftNA 03 PSMC2 ATPase, 2 famiiisris similar to 26S protease regulatory proteasome subunit SA (TAT-bindin^ (prosome. protein I) (T8P-1) {Proteasome subunst macropain)
Cfa.3960,1 PSO); transcript variant Z XM 8555 26S subunit, ,A1 s at 9.11E-04 1.15E-O2 0.71 (LOC475980); ITiRNA 82 PSMC3 ATPase, 3 proteasome
PREDlCTED; Cams (prosome,
CfeAffx.19 familiaris similar to proteasome 26S ATPase maαopain) 069.1. S1 s subunit δ (LOC478S22); XM 5357 26S subunit. l.G4€-03 1.31E-O2 0.7 mRNA 01 PSMC6 ATPase, 6
PREDICTED: Cams proteasome familiaris similar tø (prosome. proteasome (prosome; maαopain)
CfaAffec.15 mscropaln) 26S subunit; 26S subunit, non-ATPase; 14; 655.1.S1 S transαipt variant 2 XM 5359 non-ATPase,
4,12E-M 9.68E-03 0.72 aOC478765); mRNA 31 14
234 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Canis famsliaris similar to PiOtsasome activator comptex subunit 2 tPfoteasαm* activator 28- bβta sutsurύt) (PA28bβta) (PA23b) (Activator of proteasome muftScatalytic protease (prosome, subursit 2) (IiS regulator maαopain) complex beta subunit} activator (REG-beta); transcript
Cfe.2102.1 variant 3 (LOC480258); XM S550 subunit 2
,A1 s at 5.98E-(M 1.04E-02 072 mRNA 30 PSME2 (PA2B beta)
PREDICTED: Cams famϋiaris similar to Proteasome activator complex subunit 2 (Pfoteasoma activ3tor 28- beta subunit) {PA28beta) (PA28b) (Activate of proteasome muitScatalyttc protease (prosome, subursit 2) (IiS regulator maαopain) complex beta subunit} activator (REG-betβ); transcript
Cfe.14895. variant S (LOC4802S8); XM 8551 subunit 2
1.A1 s at 1.43E-02 2.69E-02 072 mRNA 06 PSME2 (PA28 beta) proteasome
PREDICTED. Cams (prosome, familiaris similar to macropain) proteaseome (prosome; activator macropaiπ) 28 subunft; 3 subunit 3 (predicted); transcript
Cfe.7938.1 variant 6 (LOC4805.2); XM 8527 (PA28 ,A1 S at 3.48E-0S 7.SSE-O3 076 mRNA 57 PSME3 gamma; Ki)
PREDICTED.' Cams proteasome familiaris similar to (prosome. proteasome (prcsome; mscropaln) activator macropain)
Cfa.552.1, subuπtt 4 (LOC474S94); XM 5318 activator A1 at 6.07E 03 1.S7E-O2 0.74 mRNA 23 PSME4 subunit 4
PREOICTED: Cams proteasome familisris βimilsr to tumor (prosome, necrosis factor supetfamlly; member 5- maαopain)
Cfa.1635β. indueed protein 1 XM 5373 assembly
LSI at 3.6S€-02 4.28E-O2 0.75 (UXHS0215); mRNA 40 PSMG2 chaoerone 2
PR6D1CTED-. Csnls proteasome tamiiieris similar to tumor (prosome,
CfaAffx,26 n«cross factor supetfamily; member 5- maαopain) 795.1.S1 s lnrhiced ptt>teln J XM 5373 assembly at 4.16E-02 4.60E-02 OJS (LOC4S0215); mRNA 40 PSMG2 chaperone 2 famlHarts similar to porypyrimidine tract polypyrirrtidin binding protein 2; e
Cfa.2529.1 transcript variant 4 XM 8617 tract binding ,S1 at 3.696-02 4.31E-O2 0.75 (LOC490149); mRNA 27 PT8P2 protein 2
Cams familβπs prostaglandin prostaglandin E2 receptor
Cfet.3452.1 EP4 subtype mRNA; PTGER E receptor 4 .51 s at I.3OE-02 2.S7E-02 074 complete crfs AFi 77934 4 (subtype EP4)
235 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000237_0001
236 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED- Ma∞ca RAB11 family muiatta RABn family interacting interartirrø proϊeifi 2
Cfa.2682,1 (class I) (RA311F1P2); XM 001 1 RAB11F protein 2
.S1 at 7.33E-02 6.326-02 0.7S roftNA 00265 IP2 (class I)
PREDICTED: Canis RAB 11 family fβmiliaris similar to Rβbl 1 interacting family -interacting protein
Cfa.10588, 2 {Rabll-BP2) (NRtplJ) XM 5350 RA811F protein 2
1.A1 at 5.566-03 1.82E-O2 0.71: (LOC477834); mRNA 26 IP2 (class I)
PREDICTED: cams RAB11 family
CfaAf1x,18 farmliaris simitar to Rβbll family-interacting protein interacting 629.1.S1 s 1 (Rabt J-FlPJ) (NRipll) XM 5350 RAB11F protein 2 at 2.03E-02 3.17E-O2 0.77 (L0C477834), mRNA 26 IP2 (class I)
PREDICTED-. Canls RAB18. faniiliβris similar to Res- member RAS related ptotøn Rab-lβ;
Cfa.1642,1 transCTip* variant 2 XM 6436 oncogene,
.S1 at 3.S9E-03 1.636-02 0.73 (LOC4θ540δ); mRMA 76 RAB 16 family
PREDICTED: Canls RAB18,
CfeAfix.21 familiaris »mitor to Res- related protein Rab-18: member RAS 132.1.81 s transCTlpt vβriβnt 6 XM 8521 oncogene at 2.78£-03 1,48E-Oi 0.74 (100195408); mRNA 30 RAB18 family
RAB20.
PREDICTED: Cams famillaris similar to Ras- member RAS
Cfe.5183.1 related protwn Rat>-20 XM 5426 oncogene
,A1 at 6.676-02 5.99E-O- 0.7 (LOC485S49); mRNA 68 RAB2Q family
PREDICTED: Pan RAB2A, troglodytes stmilar tc GTP' binding p,-otβin; transcript member RAS
Cfa.3880.1 variant 2 (LOC464197); XM 0011 oncogene
.A2 at 3.97E-03 1.64E-02 0.72 mRNA S8192 RAB2A family
RAB5A.
Cfamiliaris GTP-bincing member RAS
Cfa.3879,1 protein (rabS) mRNA; oncogene .S1 s at 5.17E-03 1.796-02 0.72 complete cds M35520 RAB5A family
PREDICTED: Cams RAB6A,
CfaAffx.93 fβmiliails similar to Ra* relβted protein Rab-6A member RAS 33.1.S1 s (Rab-6); tfanβtript variant XM 8560 oncogene at 1.29C-03 1.2JE-0. 0.73 2 {LOC6033.0}; mRNA
RAB8A.
PREDICTED: Cams fβmiliaris RA68A; member member RAS
Cfa.3637.1 RAS oncogene family XM 8504 oncogene
-S1 s at i.ise-02 2.4SE-02 0.72 (RASSA); mRNA 76 RAB8A family
PREDICTED: Canis RAB8B. familiaris sitnilar to RASSS; member RAS member RAS
Cfe.15215. oncogene family XM 8481 oncogene
1.A1 at 4.32E-04 9.786-03 0.73 (UXTδSOδOl); mRNA 35 RAB8B family
RAB9A.
CfaAfftc.16 PREDICTED: Canls famιliaιi5 fβb9 GTP- member RAS 264.1. Si s blrtding protein (RAB9); XM 5379 oncogene at ..29E-03 1.236-02 mRNA 56 RAB9A family
237 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED- Cants Rab
CfeABx.31 I familiβriε sirwlβr to P.sb α geranylseranyftransferase eranylqβranvl 221.1.31 ai ; beta subuntt 8504 RABGG transferase. t i 2.07E-03 1.3S6-O2 0.69J(UX6S2683); mRNA 11 TB beta subunit
PREDICTED: Cams Rab
CfaAfJx.31 familiaris similar to R*b cj gcranytøeranyttransfcrase eranylqeranyi 221.1.S1 s ; b«ta subunit XM 8504 RABGG transferase, at 3.62E-03 1.60E-02 0.68l(lOC6S2683); mRNA 11 TB beta subunit
PREDICTED: Cante RAD17 familiaris similar to RAD17
Cfa.12356, homolog tsoform 2 XM 5352 homolog (S,
IAI at 3.00E-03 1.51E-O2 0.75 (UXH7S088); mRNA 65 RAD17 pornbe)
PREDICTED: Cams familiaris similar to Double -strand-break repair protein rad∑l rrømotog (HHR21) (Nuclear matrix protein J) RAD21 (NXP-X) (SCCl homolog};
Cfa.1703.1 transαipl variant 3 XM 8559 homoloα (S.
■A1 at i.<M€-02 2.34E-O2 0.77 (IOC482O2.); mRNA 24 RAD21 pombe)
PREDICTED. Cams RAD50 fβmillarts similar to RADSO
Cfa.S07.1. homolog lsoform 1 XM 5319 homolog (S. A1 s at i.osε-04 8.90E-O3 0.69 (LOC474674); mRNA 01 RAD50 cerevisiae)
RAEi RNA αaAffx,16
Homo sapiens mRNA export 1 719.1. S1 s export protein (RAEl) homolog (S.
3.10E-03 1.S3E-O2 0.77IrT)RNA; complete cos U84720 RAE1
RNA binding protein. autoantigenic
PREDICTED: Canlsi (hnRNP- familiaris similar to RNA- binding protein Raiy associated (hnRNP associated with with lethal letha! yeiiov; protein) (Maternally wφfessed yellow
Cfa.16557. rrnRNP C-reiated protein) XM 5429 homolog
1.S1 at 9.39E-03 2.24E-O2 0.76 (LOC485345); mRNA 69 RALY (mouse)) fβmillarts similar to RAN- bifiding protein 2-iike I
Cfa.550.1, βoform 1 {LOC474S39>; XM 5317 RANBP RAN binding S1 s at 1.96E-02 3,t2E»02 0.72 mRNA 68 2 protein 2
CfaAHx.15 I PREDICTED: <zsm$ familiaris similar to RAN 465.1. S1 al binding protein 9 XM 5358 RANBP RAN binding t i i.σsε-02 2.31E-O2 0.76 (lOO?7S728); mRNA 93 θ protein 9
RAP1B. member of
PREDICTED: Cams RAS families similsi to RAS
Cfa.1011,1 related protein Ib XM 6461 oncogene
,S1 s at Ϊ.18E-03 1.21E-02 0.7S (LOC60898.J; mRNA 57 RAPIB family
RAP1B, member of
PREDICTED-. Canls RAS famiiieris similar to RAS
Cfa.21068. reiatβct pfotan Ib XM 8461 oncogene
1.S1 s at 2.32E-03 1.396-02 0.75 (UX608981); mRMA 57 RAP1B family
238 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000240_0001
239 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000241_0001
240 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Canis farmiiarts simitar to Activator 1 38 kOβ subunit (Replicator! facto C 3S kDa suϋunlt) (Al 38 kDa subunit) (RF< 38 replication kDa subunit) (RTC3S) factor C (Replication factof C
Cfa.14188. subunit 3) (IOC477308}; XM 5345 (activator 1 ) 3.
1.A1 a at 8.246-03 2.12E-O2 0.76 mSMA 00 RFC3 36kDa
PREDICTED. Cams famlllarls similar to Activator I 38 kDa suburit {Rβpiication factoi C 3S kOa subunit) (Al 38 kDa subunit) (RF-C 38 replication kDa subunit) (RFC38) factor C (Replication factor C
Cfa.1418β, subunit 3) (LOC477308), XM 5345 (activator 1 ) 3,
2.A1 s at 2.0SE-03 1.35E-02 OJS mRNA 00 RFC3 38kDa
PftEDICTED: Cams famlllarls similar to Activator I 37 kDa subuπtt (Replication fβctof replication C S7 kDβ stlhtiπlt) (Al 37 factor C kDa subunit) (RF-C 37
Cfa.17148. kDa subunit) (RFC37) XM 5358 (activator 1) 4,
1.S1 s at 6,<W£-02 S.6S6-02 0.77 (UX47S667), inRMA 37 RFC4 37kOa familisris sirnilsr to
CfeAffx,22 constitutive ring fing photofjrcwphαgenic er and 037.1. S1 s protesn l (LOC48006C); XM 5371 WD repeat at i.osε-os 1.20E-02 0.77 mRNA 81 RFWD2 domain 2 familisris sirnilsr to mrtoctiondrsal Rho 1; ras homoloα
Cfa.577.1, ttartscrlpt variant I XM 5377 pene family, A1 at I.09C-03 1.20E-02 0.73 (LOC4S0613); mRNA 33 RHOT1 member T1 required for meiotic nuclear
PREDICTED: Cams division 5 familiaris similar to
CfaAfix,13 CS329S-?A (LOC474643); XM 5318 RMND5 homoloα, 8 (S. 20.1.S1 at I,18E-02 2.46E-02 0.76 mRNA 73 B cerevisiae) ribonuclease L
(2'.5'- oHqoisoad
CarMs lupus familians enyl
Cfa.17844. ribcnυdease L (RNAScL) DQ49716 ate synthetase
1.A1 at 5.326-02 5.28E-O- 0.7^mRNA; complete cάs 3 dependent) familiails similar to nrtg finger protean ill;
Cfa.1781.1 transcript variant 5 XM 8592 ring finoer
.S1 at i.4ie-02 2.68E-O- 0.77 (IOC478323); mRNA RNF111 protein 11 1
CfeAffx.17 familiaris similar to Zinc finger protertn 364 475.1 -S1 s (Rabring 7) (LOC612S18); XM 8452 rino fmoer
4.436-04 9.78E-O3 0.76 mRWA 09 RNF115 protein 115 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000243_0001
242 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famillarts similar to large riboso subuπit nbosomat protein mal
Cfa,3214,1 U63 (LOC4803H); XM 5374 RP136A protein L36a-
.51 a at 4,99E-M 1.00E-02 0.62 mRNA 33 like famillaris similar to large riboso subuπit nbosomai protein mal
Cfa.3214.1 L36ϋ (LOC4S03I1); XM 5374 RPL36A protein L36a-
,S1 s at 3.28E-CM 9.2SE-03 0.64 mRNA 33 like
CfaAffx.30 KKtUIl-I tU.' WIOiS famillaris Ribosomal
225.1, S1 s protein L7a (RΛ7A); XM 5378 Ribosomal at i.326-03 1.23E-O2 0.76 mRNA 00 RPL7A protein L7a familiaris similar to Dolldiys- diphosphoollgosaccriaride- -protsm gtyrosyitransfisrssf 67 kOa subuntt precursor (Ribophoriπ J) (RPN-I);
Cfa.9914.1 transcnpt variant 1 XM 5337
,S1 s at 2.386-03 1.40E-O2 0.74 (LOC476516); mRNA 22 RPN 1 ribophorin famiiisris similar to DoOchyi- dtphosphooligosaccharicte -protein grycosYttransfersse 67 kD3 subunit precursor (Ribophorifi I) (RPN-I);
Cfa.9914.2 transcript variant 3 XM 8437
.A1 s at 2.78C-03 1.48E-02 0.74 (LOC476516); mRNA 37 RPN1 ribophorin farmliarts similar to ribophorin U precursor;
Cfe.1364.1 transcript variant 3 XM 8605 ,A1 at 9.00E-02 7J3E-O2 0.75 (LOC477223); rr.RNA 86 RPN2 ribophorin Ii fβmiliarts similar to nbcphonn π precursor;
Cfa.21586. transαipt variant 3 XM 8605 1.S1 s at 4.46E-(W 9.79E-03 0.74 (LOC477223); mRNA 86 RPN2 ribophorin Ii
Regulation of
PREDICTED. Pan nuclear pre-
CfeAffx.27 I troglodytes similar to PlSRS protein; transσipt mRNA 347.1, S1 al variant I (IOC4G8522); XM 0011 domain
L 2.50€-02 3.50E-O. 0.74 mRNA 36295
Figure imgf000244_0001
containing 1A
Cfa.1201.1 Riso5cmai protein S17 Ribosomal ■A1 S at 3.266-03 1.55E-O2 0.73 (rpSi7 g«ie) AJ388523 RPS 17 protein S17 ribosomal
PREDiαED: Canis prot farwliaris hypothetscal ein S19
Cfe,6966,1 LOC474S02 XM 5317 RPS19B binding
.A1 at 1.41E-04 8,90E»03 0.67 (LOC474502); mRNA 30 P1 protein 1 ribosomal
CfaAf6t,28 PREDICTED-. Osπls faniilisris hypothetical protein S19
77.1.S1 s 101047^SOi XM 5317 RPS 19B binding
2.S4E-03 1.44E-02 0.7 (LOC474502), mRMA rotein 1 familiails similar to 4OS
Cfa.732.1. ribosomal protein S20 XM 5350 ribosomal S1 s at 2.50€-0<* 9.06E-O3 0.66 (LOC-177887); mRNA 79 RPS20 protein S20
243 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000245_0001
244 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000246_0001
245 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDlCTgD: OmIS sterile alpha familisris similar to sterile alpha motif domain motif domain
CfaAfix,39 containing 9-llke XM 5394 SAMD9 containing 9- 29.1.S1 at Ϊ.SSE-OΪ 2.80E-02 Q.76|(IOC4S2305); mRNA 22 L like sorting and assembly machinery
PREDICTED: Cams co familiaris sirrsilar to SAM50 mponent 50
Cfa.11724. like protein CGI-51 XM 5317 SAMM5 homolop, (S,
1.A1 S Ϊ.8SE-04 9.00E-03 0.67 (IOC47Η73); mRNA 02 0 cerevisiae)
PREDICTED: Mscacs SAM domain. muiatta SAM ciomain; SH3 SH3 domain
CfaAffx.12 domain and nucJβar and nucl kxaiteatfon signals; 1; ear ■ 1.S1 s transcript vartant 3 XM 0010 localization
JL 4.70E-03 1.73E-02 074 (SAMSNl); mRMA signals 1
PREDICTED: QmIs Sϊn3A- familiaris similar to sin3
Cfa.4066.1 Λssodated polypβpbde XM 5345 associated
,A1 s at 1,7SE-OS 7.S5E-03 0.72 plS (LOC609404); mRfvA 36 SAPi 8 protein, 18kDa
CfeAffx.12 I Pft£DICTεD. Cams Sin3A- familiaris similar to sln3 592.1, S1 al sssoclatsa pol^eptide XM 8439 associated t i 3.99C-02 4.49E-02 0.77 p30 (LOC6073S9): mftKA 90 SAP30 protein. 3OkDa
PREDICTCD: Cams farmliaris similar to 6TP- SAR 1 a biwiing protein SARIb ene
Cfa.3394.1 (GTBP8) (LOC481509); XM 5386 homoloq B (S.
.A1 at S.13E-03 1.7SE-02 0.7S mRNA 30 SARIB cerevisiae)
PREDICTED' Canis tamillarfs similar to GTP- binding p<iote)n SARJb SAR 1 flene
CfaAffx.24 (GTBPB) (LOC48JS09): XM S386 homoloq B (S. 33.1.S1 at 2.46E-03 1.41E-02 0.75 mRNA 30 SAR1B cerevisiae)
PREDICTED: Cams
CfaAffx,24 familisns sιrn:lsr to GTP- SAR 1 g bindinξ protein SARIb ene 33.1.S1 s (GTBP8) (LOC481S09); XM 5386 homolop B (S. at I,08E-03 1.20E-02 0.72 mRNA 30 SARIB cerevisiae) familiaris slmilai to Shwachman- Shwachman-Bodlan Bodian- Dβmond syndrome
Cfa.17197. protein (UOC607017); XM 8435 Diamond
1.31 at S.22E-03 1.79E-02 0,77 mRNA 39 SBDS syndrome famiiiaπs simitar to Shwachman-
CfaAffx.16 I Shwachman-Bodian- Bodian- Dlsniond syndrome 922.1.S1 a! protein (LOC607017); XM 8435 Diamond t 6,76E-(M i.xaε-oa 0.7 mRNA 39 SBDS syndrome
PREDICTED: Canls strawberry
CfeAffx.12 familiaris similar to sno; notch straΛ'berry notch hcxnotog 131.1.S1 s 1; transcript variant 1 XM 5346 homoloα, 1 at 3.27£-04 9.28E-O3 0.64 (IOC1774S1); mRNA 49 SBNO1 (Drosophila)
246 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000248_0001
247 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREOICTSO: Can* famsliaris similar to Stromal ceMe-ived factoi 2-like protein 1 precursor stromai cell- [SDF2 iike protein 1}
Cfa-8688,1 (PWPl-mteractirsg, protein XM 8457 derived factor
.A1 s at 4.S9C-03 1.75E-O2 0.7f 8) (LOC608633); mRNA 1? SDF2L1 2-IiKe 1
PREDICTED: Cams familiaris similar to Stromal celi-derr>-ed factet
CfeAffx.23 2-IiKe protein i precursor stro (SDF2 like protein 1) mal cell- 546.1 -S1 £ (iWi-mterscting protein XM 8457 derived factor
L i.θsε-03 1.31E-O2 0.67 8) (LOC6G8633), mRNA 17 SDF2L1 2-like 1
PREDICTED: Canis fanύliβris similar to Succinate dehydrogenase succinat [ubiquinone] ffswpfotein e sυbυnit; mitothorxiriat dehvdroαenas precursor (Fp) e complex, (Plβvoprotefn subunit of subunit A, complex M); transcript
Cfe.16281. variant 6 (IOC478634): XM 8518 flavoprotein
1.31 at 4.53E-02 4.S6E -02 0.7S r»RNA 44 SDHA (FP)
PREDICTED: Cams famtliaris similar to Succinate dehydrogenase JubJquliione] iron-sulfur succinate pititein; mitoeiiondrfB1 dehvdrogenas
CfeAf&(.24 precursor (ip) {Iron-sulfur subunit of complex If); e complex, 257.1. Si s transσipt variant 1 XM 5353 subunit S, iron at 7.296-04 1.08E-O2 0,77 (LOC47S217); mRNA 92 SDHB sulfur (ip)
PREDICTED-. Canls familiaris similβr to Succinate dehydrogeMse succinate [ubiquinone] i«on-sulfur dehvdrogenaβ
CfaAffx.33 protein; mltocrtondrla, precyrsβr (Ip) (Iron-sulfur e complex, 71.1.81 s subunit of eompiex H) XM 8451 subunit B. iron at S.52E-04 1.02E-O2 0.74 (IOC608210); mRNA 69 SDHB sulfur (ip)
SEC22 vesicle
PREDlCTED: Canls trafficking
CfaAflx.16 I familiaris similar to SEQ2 prot vesicie trafficking protein- ein 788.1.81 al like 1 (LOC475816); XM 5330 homoloα, B (S. t i 1.086-03 1.32E-O2 0.77 mRNA 25 SEC22B cerevisiae)
SEC22 vesicle
PREDICTED: Canls trafficking
CfeAflx.16 familiaris similar to SEC22 prot vesicie trafficking prβteirv ein 788.1.81 s like 1 (LOC475816); XM 5330 homolopi B (S. at 3.0SE-03 1.51E-O2 0.71! mRNA 25 SEC22B cerevisiae)
248 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
SEC23
Pongo abeln mR*!A; CDMA
Cfa,319.1, DKFZfM69D0613 (from interacting A1 at 6.51E-03 1.93E-02 0.76 Clone 0KFEp469DO653) CR859634 protein
PREDICTED: Canis familiaris similar to SEC24 related Pixjtein transport protsin gene family, S«c248 (SEGM-reJated
Cfa.585.1, protein B) (LOC467S96); XM 5450 member 8 (S. S1 s at 2.046-02 3.17E-O2 mRNA 21 SEC24B cerevisiae) flfα ItJt! !OaSl » pfvACiπ translocation complex
Cfa.3695.1 beta subunit mRNA; Sec61 beta ,A1 s at S.?9eO4 1.03E-02 OJIi comptete «)s L25052 Sec61b subunit
CfaAffx.65 fβmiliails similar to Traαstocation protein 74.1.S1 s SEC63 homoiog XM 5322 homoloα (S. at i.636-04 9.00E-O3 0.61 (LOC47S016); mRNA 52 SEC63 cerevisiae)
Sθl-1
PREDICTED: Canis suppr familiaris similar to s«f- 1 essor of
Cfe.18769. suppressor of lln-12-lιke XM 5375 lin-12-iike (C.
1.S1 s at 7.1SE-03 X.99E-02 076 (I.OC480409); mRNA 30 SEL1L eleqans)
Cfe,4366,2 selerioprotein K (SElK); NM 0011 selenoprotein ,A1 at 6.32E-(M l.UE-02 0.63 mRNA 14878 S£LK K
CfeAffx.95 Cani- lupus familiaris 5.1 -S1 s a sβtenoprotβin K (SEtK); NM 0011 selenoprotein t 3.ΘS€-0<> 9.61E-O3 0.66 mRWA 14878
sema domain, immunoqlobυli n domain (iq), transmembran e domain (TM) and short cytoplasmic αaAf&(.41 PReDlCTED: Canis ftimiliaris sitnilar to domain, 64.1.S1 s semβphorin 4D XM 5335 SEMA4 (semaphorin) at 2.32E-03 1.39E-02 0.76 (I.OC476350); mRMA 51 D 4D
CfaAffx,20 i familiaris similar to SUMOI/sentri SUM01/s«f tnn specific 279.1. S1 ai protβas? S (LOC438033); XM 5451 n specific t ! 7.7JE-W l,tOE»O2 0.74 mRNA 56 SENP5 peptidase 5 ftimiliaris similar to setefiophospbate s synthetase, transcript elenophosph
CfaAffx,80 v-srwnt 1 (LOC477999); XM 5351 ate synthetase 46.1.S1 at I.9OE-0S 7.SS6-03 0.76 mftNA 83 SEPHS1 1 farπilisiis similar to selenophosphate synthetase; transcript selenophosph
Cfa.408.1. variant S (LOC477999),: XM 8523 ate synthetase A1 at 3.466-04 9.40E-O3 0.72 mRNA SEPHS1 1
249 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000251_0001
250 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Cams splicing factor. famillaris similar to arqinine/serin splicing factor; e-rich 10 srgmme/senne-nch JO (transformer 2 (transformer 2 homoiog;
Cfa.4472.1 Drosophila) (L.OC478663); XM 5358 homoloq,
.51 at I.60E-03 1.27E-O2 0.72 mRNA 33 SFRS10 Drosophila)
PREDICTED: Cartis spljdng.factoL fβmiliaris similar to arginine/serin splicing fβctof; e-rich 10 srgimne/sefSne-neh XO (transfor (transformer 2 homoiog; mer 2
Cfa.4472.1 Drosophila) (L.OC478663); XM 5358 homoloq ,
.51 s at i.56£-03 1.26E-02 0.74 mRNA 33 SFRS10 Drosophila) ftimiliaris similar to spltcmg factor; splicing factor. argiπirsθ/serine-flch 11;
Cfa.9497,1 transcript variant 4 XM 8626 arqinine/seiin ,A1 at 9.96E-03 2.30E-02 0.76 (LOC490216); mRNA 55 SFRS11 e-rich 11
PREDICTED: Cams families ttyμυtiHKical LOC47S00S; tra*iscript splicing factor
Cfa.15354. variant 14 (UOC47S005); XM 8630 aroinine/serin LSI s at Ϊ.82E-02 3.01E-O2 0.72 mRNA 95 SFRS18 e-rich 18
PREDICTED: Cams farroϋaris similar to Spl'cing factor; a!5ln:ne/se(ine-rich Z
CfaAfftt,86 (Splicing factor SC3S) (SC splicing factor. 35) (Spiidng component; 58.1.81 S 35 kDa); ttaiwtπpt variant XM 8438 arqinine/serin at 3.3SE-04 9.286-03 0.67(2 (LOC612817); mRNA 96 SFRS2 e-rich 2
PREDICTED: Cams fβmiliails similar to Splicing factor; βrgfmne/sβfine-nch 2 (SpJicing factor SC35} (SC 35} (Slicing cof»ponent, splicing factor.
Cfa.1060S. 35 kDa); transcript variani XM 8526 arpinine/serin
1.S1 at 7.69E-(M l.tOE-02 075 5 (U3C612817); mRNA 79 SFRS2 e-rich 2 splicing factor. arqinine/seiin
Homo βapsens spJscine e-rich 2, factor; argininβ/serinβ* αa.2367.1 rich 2; interacting puitein NM 0047 interacting ,A1 at 2.936-03 l.SOE-02 (SFRS2IP); mftMA 19 protein splicing fector,
PREDICTED: Cams
Cfa.246.1, famillarts splicing factor XM 5321 arqinine/serin 81 s at 1.276-04 8.9OE-O3 0.69 (SRP20); mRNA 24 SFRS3 e-rich 3 splicing factor.
PR6DICTED; Canis
CfaAHx.30 fanύliβris splicing factor XM 5321 arginine/serin 02.1.SI at 9.016-(M l.tSE-02 0 76 (SRP20); mRNA 24 SFRS3 e-rich 3 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
farrnllaris similar to SpEcirse factor; avgmine/serine-iich S (!Ve mRNA splicing factor SRNO) (Insulin-induced growth response protein O.-45 (Deiayed-eβrly splicing factor. protein HSS); transcript
Cfa.12115. variant S (IOC4907S4): XM 8620 arojnine/serin
3.A1 s at 6.796-03 1.96E-O2 0.76 mSMA 00 SFRS5 e-rich 5
PREDICTED: Cams splicing factor. familiaris s>ιm:t<»ι to splicing factor; arpinine/serin
Cfa.11128. srginme/serine-neh 7 XM 5329 e-rich 7,
2.A1 s at I.13E-02 2.41E-O2 0.76 (L.OWS730); mRNA 39 SFRS7 35kDa
PREDICTED-. Csnls splicing factor,
CfaAfftc.10 familieris similar to aigjnjn splicing factor, e/serin 413.1.S1 s argimne/serine-rich 7 XM 5329 e-rich 7.
1.49€-02 2.74E-02 0.7^(LOC47S730); mRMA 39 SFRS7 35kDa
PREDICTED. Cams famfllarts similar to Aipha- sat«ogh/can precursor sarcoqlvcan, (Alpha-SG) (Adhalln) (50 alpha (5OkDa
CfaAfTx,26 I kOa dγstrophirt-essøciiited dvstrophin- glycoprotein) (50DAG) Q23.1.S1 ai (Dystrogfycan 2) XM S464 associated t 8J1E-03 2.13E-02 1.31; α<XS09265); mRMA 94 SGCA glycoprotein) sarcoqlvcan, gamma
Canis lupus famlDaris (35kDa sarrøglγcan; gamma dystrophin- (3SkDe dystroptiin- αa.6416.1 associatβd glycopro'e.n) NM 0010 associated .A1 at s.asε-05 8.S0E-03 1.32 (SGCG); mRNA 14276 SGCG glycoprotein)
PREDICTED: Cams familiaris similar to SH3 domain-binding protein S SH3-domain (SH3 domaϊn-binding binding protein that preferentially
Cfa.2341,1 assoαatβs with 8TK) XM 5427 protein 5 (BTK ,A1 at 1.02E-02 2.32E-O2 0.71 (LOC48S6S7); mRNA 77 SH3BP5 associated) familianβ similar to 26 proteβsome complex subunlt DSSl {Deleted In split hand/spiit foot protein 1) (Split hand/tbot split hand/foot
CfaAffec.41 deleted protein l homotog)' transcript malformation 60.1.S1 s vsiiatΛ 1 (LOC6Q8719); XM 8452 (ectrodactyly) at I.61E-02 2.WE-O2 0.75 mRNA 85 SHFM1 type 1 familiaris similar to Leucine-iich reiieat soc-2 protein SKOC-2 (Ras- suppr bifidiDg protein Sur^s;, essor of
Cfa.21077. tr«nscnpi variant 2 XM 8595 clear homolog
1.31 s at 2.92E-03 1.50E-02 0,77 (LOC477S19); mRNA 10 SHOC2 (C. elegans)
252 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Carts supβfkiljer. famiHaiis similar to viralicidic supeiKlller viraiiddie activity 2-like activity 2-like 2; transcript
Cfa.2346.1 variant I (LOC6079S0): XM 8445 2 (S.
-A1 s at 3.66£-03 1.4SE-02 0.66 mRNA 83 SKIV2L2 cerevisiae) solute carrier family 11 (proton-
Cams lupus families coupled, solute earner family 11 divalent metal (proton -coupied divalent ion metal son transporters),
Cfa.14639, member 1 (SLCIlAl); NM 0010 SLCH A transporters).
1.S1 at ..32E-02 2.596-02 1S mRNA 13851 1 member 1
PREDICTED: Canis famϋiaris similar to Scluse cactier family 12; member solute carrier 2 (Sumetanide-sersitλ'β family 12 sediurrK potassium}- (sodium/potas
CfeAffx.18 chloride cownsporter 1) siu (Basolatera! Na-K-O m/criloride 85.1.S1 s syroportef) (LOC481490); XM 5386 SLC12A transporters), at 2.(Mt-Oa 3,I7fc-O2 075. roRNA 11 member 2
CfeAffx.12 PREDICTED. Cams solut familiails similar to solute e carrier 315.1. Si s earner family 25; menber XM 5342 SLC25A family 25. at i.sτε-03 1.26E-02 0.72 36 {IOOOT09S}; mRKA 89 36 member 36 famillaris similar to
CfaAffx,14 mitochondrial soiute solut camef-iike protein; e carrier 394.1.S1 s transαipt variant 5 XM 8537 SLC25A family 25. at 2.«7e-02 3,4SE-OZ 0.77 (LOC4S6..5); mRNA 61 37 member 37
CKtuititu.' <*anis famillaris similar to solute carrier
Cfa.2658,1 O-8931-?A (l0C488-76); XM 5459 $LC25A family 25. .S1 at S.48£-04 1.02E-O2 0.7^ mRNA 93 46 member 46 solute carrier family 25 (mitochondrial carrier;
PRtUICTtD: Canis adenine familiaris sirnitar to solute carrier family 35; member nucleotide
Cfe.1352.1 S; trarβcrifrt vartom \ XM 5492 SLC25A translocator).
.51 s at 9,81E-M i.teε-02 0.76 ILOC492093); mRMA 15 member 5
PREDICTED: Canis farwliaris similar to Very- solute carrier taι>9-cS\airt acyl-CoA family 27 (fatty synthetase ( Very -long- acid chain-fatty-ac K)-CoA
Cfa-13≥27. ligase); tfanseript variant XM 8571 SLC27A transporter).
1.A1 s at 2.22E-02 3.316-02 0.66J2 (LOC47S298); mRNA 61 member 2 solute carrier family 33
PReOlCTED: Pan (ac troglotfytes acetyl- etyl-CoA
Cfa.593.1, coenzyme A transporter XM 5168 SLC33A transporter). A1 at 1.70E-03 1.29E-02 0.67 (SLCJ3A1); mRNA 31 1 member 1
253 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000255_0001
254 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000256_0001
255 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
SWI/SNF related, matrix
PREDICTED: Canis associated. famillarts similar to SWI/SNF related; matrix actin associated; actin dependent dβperxJent reguiator of regulator of chromatin; subfamily e; chro member l; transcript matin,
Cfa.8883.1 variant 8 (LOC60S2S0): XM 8579 SMARC subfamily. e,.
■A1 at 3.536-02 4.21E-O2 0.7S mRNA 12 H member 1
SWI/SNF related, matrix
PREDICTED. Cams associated, famillarts similar to actin SWI/SNF related; matrix associated; actin dependent dependent regulator of regulator of
CfaAffx,24 I chromatin; subfamily e; chro member 1; transcript matin, 592.1.S1 ai variant B (LOC60B250); XM 8579 SMARC subfamily e. t 5.77E-02 S.S3e-02 0.74 mRNA 12 E1 member 1
PREDICTED: Cams famιliari5 similar to Structural maintenance of chromosomes 4-l*e 1 protøn (Chromosome- structuiBl sssodatea fwl^ieρtκ3e C) maintenance
CfaAffx.22 (hCAP-C) (XCAP-C horrtolog); transcript SL i.1. S1 s variant 2 (LOC478679); XM 8564 chromosomes at β,9OE-03 2.19E-02 0.74 mRNA 36 SMC4 4
PREDICTED; Cams famϋiaris simitar to Strurtural maintenance of chromosomes 4-like 1 protein (Chroffrøsotr^- structural associated polypeptide C) maintenance (KAP-C) (XCAP-C homolog); transcript St
Cfa.1060,1 variant 3 '(LOC478679): XM 8564 chromosomes •S1 at 7.016-03 1.98E-O2 0.68 mSMA 4
SMEK homolop 1.
PREDICTED; Cams suppressor of
CfaAffx.26 I fβmiliaris simitar to CG9351-PA; lsoform A; mek1 ■ 1.S1 ai transcript variant 2 XM S633 (Dictγoste)ium t I.52E-02 2.76E-02 0.76 t_OC$.2974); mRMA 66 SMEK1 )
PREDICTED. Cams sphingomyelin famillarts similar to acid sprilngomyefcnase-like phosphodieste
Cfa.15673. phosphodiesterase 3A XM 5334 SMPDL rase, acid-like 1,81 at 1.9SE-02 3,ttE»02 0.7 (LOC476279); mRNA 85 3A 3A
PREDICTED: Canis sphingomyelin
CfeAfix.23 famillarts similar to add phosphodieste sjjhingorøyefinaseHikfi
3.1.S1 s phosphodiesterase 3A XM 5334 SMPDL rase, acid-like at 8.6i6-03 2.17E-O2 0.7_ (LOC476279); mRNA 85 3A 3A
256 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000258_0001
257 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
πexm 18 (SNX18);
Cte.1S561. transcrtot variant I; NM 0011 soiling nexin
1.S1 at ..3OE-02 2.57E-O2 0.72 roRNA 02575 SNX18 18 familiariδ similar to Sorting nexiπ-2; transenpt αaAfix.65 variant 1 (LOC474657); XM 5318 8.1. S1 at {,626-03 1.27E-02 1.31: rnRNA 86 SNX2 sorting nexin 2
PREDICTED: Canls sorting n familiaris similsr to sortiπς exin
CfaAffx,55 nexin 7 (predicted) XM 5387 family 34.1.S1 at ..oβε-oa 2.35E-O2 0.7 (LOC4δ_672); mftNA 94 SNX30 member 30 familiaris sitiiilar to
50.1S1 s Sorting nexin-5 XM 5428 at i.26E-03 1.23E-O2 0.72 (LOC485754), rc.RHA 77 SNX5 sorting nexin 5
PREDICTED. Cams famillarts similar to Cytokine inducible SH2- containing protein S (Suppressor of cytokine signing S) (SOCS-S) suppr (Cytoicine-lnducibie SH2 essor of
Cfa.10850. protein 6) (C3S-6) XM 5318 cytokine
1.A1 s at 6.19E-03 1.896-02 0.7 (LOC4745S1), mRMA JO signaling, 5 suppr
Homo sapiens suppressor essor of
Cfa.16439. of cytokine signaling 6 NM 0042 cytokine 1.A1 at 7.076-03 1.99E-02 0.73 (SOCS6); mRNA 32 SOCS6 signaiino 6 fβimiliaris similar to SON
CfaAffx.14 DNA-»in<Slng protein SON DNA isoform A; transcript ■ 1.S1 s variant 13 (IOC47B406); XM 8520 binding at 6.6OE-03 1.94E-02 0.75 mftNA 50 SON protein familiaris similsr to SON ONA-binding ptotein tsoform A; transcript SON DNA
Cfa.10358, variant 14 (LOC47840«.>: XM 8520 binding
2-S1 s at 1.216-02 2.4BE-O2 0.76 mRNΛ item rfceerrtmay."(^aιιιiι —
CfaAf{χ.δ5 familiaris similar to spastin isoforri) 1; 41.1.51 s transcript vsrfβnt 2 XM 8577 at 6.256-03 1.89E-O2 0.7_ (IOC6QSSS2); mRNA 38 SPAST spastin fβmillarts similar to spermatooene spermatogenesis sis associated; seππe-ricti 1;
Cfe.10316. transcript valiant 1 XM 5348 associated,
1.A1 at i.SSE-02 2.79E-02 0.74 (LOC477617); mRNA 11 SPATS2 serine-rich 2
SPC24, NDC80 kinetochore
PREDICTED: Cams complex
CfaAffx,26 i famillaris similar to co spindle pole body mponent, 814.1.S1 ai component 24 homoksg XM 8488 homolog (S, t 1.10E-02 2,39E»02 0.76 (LOCSU174); mRNA 18 SPC24 cerevisiae)
258 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000260_0001
259 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000261_0001
260 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDlCTgD: Osnls familisris similar to Laβosytcβfamide alpha 2;3-elalyttransferase (CMP NeuAc-.lactαsytcerβmide s!pha-2;3- ST3 beta- sialylsransferas*) qalactoside (GangliosKfe GM3 aipha-2.3- synthase) (ST3Gsl V)
Cfa.1536S. (Slalyltransferase 9) XM 8497 ST3GAL sialvitraπsfera
LA1 at 5,24E-(M X.Oiε-02 0.7JI (U5C652022), mRMA 49 se 5 famtliaris similar to stroma! antigen 2;
Cfa.16897. transcript variant 7 XM 8S98 stroma)
1.S1 s at 146E-03 1.2SE-02 0.72 ILOC492JU); mRMA 56 STAG2 antigen 2
CfaAflx.2S I famtliaris similar to stroma! antigen 2; 426.1.S1 ai transcript variant 11 XM 8599 stroma) t I.38C-02 2.6SE-02 0.72 IIOC492JU); mRMA 49 STAG2 antigen 2
PREDICTED: Cams famιliari5 similar to MlNW N-terrniπal homolog:
Cfa.9061.1 transαipt variant 1 XM 5403 STARD3 STARD3 N-
,S1 at 4.S4E-04 9.86E-03 1S (LOC4S32S7); mRNA 76 NL terminal like
StAR-relatecl
PREDICTED: Canis lipid transfer familiaris similar to START (START) domain containing 4;
Cfe.12403. sterol regulated XM 5362 domain
1.A1 a at I.47E-03 1.2S6-O2 0.67 (LOC479141), mRMA 87 STARD4 containing 4 signal
PREDICTED: Canls transducer familiaris similar to Signal and activator
CfeAfix.23 I transducer and activator of transcription 58; of. 894.1, 81 ai transcript variant 4 XM 8549 transcription t 4.65€-03 X.73E-O2 0.74 (LOC490969); mRNA 98 STATSB SB staufen, RNA
21
PREDICTED: Pan prot tfogloclybβs staufen ein,
Cfa.57β.1. homokxj 2; banscript XM 001 1 homolop 2 S1 at 7.23B-03 2.00E-02 0.73 vartant 7 (STAU2); mRNA 65598 STAU2 (Drosophila)
PREDICTED: Pen troglodytes strtafcm; calmodulin calmodulin binding
CfaAffx,96 protein; tfanscrtpt variant XM 0011 binding 83.1.S1 at 3.88E-03 1.63E-02 0,67 2 (STRN); mRNA 66128 STRN protein
STT3, subunit
PREDICTED: Cams familiaris similar to of the Oiiξosaceharyi transferase oiiposaccharyl STT3 subunit homolog transferase (BS) (Integral membrane co protein 1); transcript mplex.
Cfa.10858. variant i (UXM89300); XM 5464 homolog A (S.
LSI at 4.35E-O3 1.7SE-02 0.74 mftNA 18 STT3A cerevisiae) Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
STT3. subunit
PReDlCTED: Canis familiaris similar to of the Gϋgosscsharyl transferase oliqosaocharyl STT3 subunit hσmolog transferase
CfaAHx.16 (BS) (Integral membrane protan I): transcript complex, 940.1. S1 s variant 1 (LOC4S9300); XM 5464 homoloo; A (S. at ..096-02 2.38E-O2 0.7<? mRNA 18 STT3A cerevisiae)
STT3. subunit of the
PREDICTCD: Cams oiiQOsaccharyl famillaris similar to source transferase of immunodominant MHC- associated peptides: complex,
CfaAffx.80 transcript variant 6 XM 8S66 hornoloq B (S. 75.1.51 at 2,94E-M 9.2SE-03 0.75 (UX45562S); mRNA 94 STT3B cerevisiae) familiaris similar to
Cfa.19362. syntaxfπ 12 {LOC4?816S), XM 5353 LSI at I.36E-03 1.23E-02 0.72 roftNA STX12 svntaxin 12
CfaAffx.18 i famiiieris similar to 679.1.Si ai syntaxin 12 (IOC578168), XM 5353 t i 2.70E-03 X.4SE-02 0.7 mRNA 42 svntaxin 12 familians similar to Svntaxin-7; transctipt
CfaAf{χ.12 vβnsnt 4 (LOO483987); XM 8540 43.1.S1 at J.SiE-03 1.2SE-02 0.64 m»NA STX7 svntaxin 7 famtliaris similar to Syntaxin-7; transciipt
Cfa.1859.1 vβnsnt 5 (LOC483987); XM 8540 .51 at I..5E-03 1.21BOZ 0.72 rnBNA 89 STX7 svntaxin 7
CfaAlix.12 famillaris similar to SyW3xir>-7; transcript
43.1.S1 s vsnant S (LOC483987); XM 8540 at 8,64E-M 1..3E-O2 0.66 mRNA 89 STX7 svntaxin 7 familiaris similar to syntaxirs 8; transcript
Cfa.SOβO.1 variant 1 (LOC479499); XM 5366 ,S1 at 9.70E-03 2,27E»02 0.7S mRNA 38 STX8 svntaxin 8 svntaxin
CfaAffx.14 PR6D1CTED-. Canls famiiieris similar to binding S.1.S1 s tomosyn isoform b XM 5334 protein 5
M 3,246-02 4.016-02 0.75 (UXT476237); mRMA 42 STXSP5 (tomosvn)
PREDICTED, Cams famillaris similar to Sucσnyf-CoA lipase [ADP- formiøg; beta-<3iaιπ; mttochondfiat precursar (Succiπyi-CoA synttietose; succinate-CoA betaA chain) (SCS-betaA) (ATP-sp«cific suctinyl-CoA liαase. ADP-
Cfa-20191. synthetase »eU subunit} XM 5425 forming, beta
LSI s at 2.05E-04 9.06E-03 0.73 (LOC4δ5448); mRNA 66 SUCLA2 subunit
262 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Cams familiaris similar to Succinyi-CoA lipase [ADP- forming} beta-cSialn; mitochondrial precursor (Sυccmyi-CoA synthetase; succinate-CoA befeiA chain) (SCS-betaA) ligas (ATP-spedflc succinyl-CoA e, ADP-
CfaAffr.76 synthetase Seta subufxt) XM 5425 forminα. beta 25.1.S1 at 778E-04 l.Xøε-02 0.7JI (U5C48544Q), mRNA 66 SUCLA2 subunit
PREDICTED: Cams families aimilsi to succinat succlrsate-CoA lipase; GDP e-CoA
Cfa.16185. forming; alpha subunit XM 5329 SUCLG ligase, alpha
LSI at 9.83E-03 2.29E-02 0.7S (IOC47S77S); mRNA 85 1 subunit
PREDICTED: Cams famtϋarts similar to Sucrinyi-CoA lipase (GDP- formlng] beta-chain: mitochondrial precursor (Succinyl-CoA synthetase; bβtaG chain) (SC5-bβw<3) succinate-CoA
CfaAffx.10 (GTP-spetific stsociπyi- CoA synthetase beta lipase, GPP- L1.S1 s -ubunit) (LOC476S62); XM 5337 SUCLG formina, beta
4.30€-03 1.68E-0. 0.76 mRNA 2
SMT3
PREDICTED: Cams suppressor of familiaris sirn'tar to SMT3 suppressor of t«iif two 3 mif two 3
Cft>.746.1. honvotoo. 1 (LOC478S74); XM 5360 homoloq 1 (S. S1 s at 2.61E-03 1.44E-02 0.73 mRNA 34 SUMO1 cerevisiae) famiiiβris similar to suppressor of Transcription initiation Ty 4 homolog protein SPT4 horrsofog 2;
Cfa.20467. transσipt vβrtβnt 3 XM 8618 SUPT4H KS.
LS1 s at ..14E-02 2.42E-02 O.δδ (LOC60$7S7); mftNA 91 1 cerevisiae)
PREDICTED: Cams familiaris sιrr«U>r to suppressor of
CfaAfftt,17 suppressof of variegation vari 4-ΪO ^moiog 1 lsoform egation 4- 055.1.S1 s Z; transcript variant 2 XM 8464 SUV420 20 homoloq 1
6.34E-03 l.St6-02 0.76 (LOC483690), mRNA 31 HL (Drosophila) suppressor of
CfeAffx,28 I PREDICTED. Cams familiaris similar to joined zeste 12 282.1.81 al to JAZPS (L0C4SSSSS), XM 5482 homolop, t i 2.14E-03 1.36E-02 0.76 mRNA 78 SUZ12 (Drosophila)
PREDICTED: Bos taurαs simiiar to Polycomb protein SU? 12 (Suppressof of εeste 12 protein homolog } (Joined to JAZ?! protein) suppressor of (Chromatin precipitated z E2F target 9 protein) este 12
Cfa.20926. (ChεT 9 protein) XM 5826 homoloq
1.S1 at 6.S2E-03 l.936-0a 0.73 (SU212); mRNA OS SU212 (Drosophila)
263 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
fBm:!laris similar to Synaptonemaf complex protein 2 (SCP-2 profcem)
CfaAfftc.19 ! (Synsptafwwal compiex svnapton lateral βfement protein) emal 115.1.S1 ai (hs5CP2) (LOC477278): XM 5344 complex
L 2.S7E-02 3.55E-O2 1S mRNA 70 SYCP2 protein 2
PREDICTED: Canis SYF2
CfaAffic.19 familiaris similar to CCNDBPl Interactor homolog, RNA
960.1.S1 s isoform 1 <U)C47βlβ4); XM 5353 splicing factor
JL l.SSE-02 279E-02 0.75 mRNA 57 familiaris similar to ssTiβptopttysin-like i
CfeAffx.69 isoform b (LOC47S889); XM 5330 synaptophystrv 11.1.S1 at I.10E-03 1.2OE-O2 0.76 mRNA 96 SYPL1 like 1 famϋlaris similar to transforming acidic celled transforming. coil containing protβir J acidic coil short isoform; transcript ed-
Cfe.6437.2 variant 2 (LOC47SS81); XM 8435 coil containing
-A1 s at 3.69E-03 1.46E-02 0.71 mRNA 72 TACC1 protein 1 transcriptional adaptor 1
CfaAf&(,23 I PREDICTED: Cams famillaris similar to SFT3- (HFM 824.1.81 al βssoctøttϊu fttctor 42 XM 5372 homolog,
L 7.996-03 2.09E-O2 0.76 (LOC480090); ftiRNA 13 TADAU veast)-)ike
TAF7 RNA polymerase H, TATA box
PREDICTED. Cams binding famillaris similar to TATA prot box-bmtJing protein- ein (TBP)-
CfaAfftt,97 sssoclatsa factor 2F XM 5443 associated 4.1.81 at i.496-02 274E-02 0.68 (LOC48718O); mRNA 08 TAF7 factor. S5kDa troglodytes T-cell scute T-c lymphocytic leukemia 1; eil acute
Cfa.2349,1 transcript variant 1 XM 0011 lymphocytic
■S1 at 2.836-02 3.73E-O2 0.73 (TALI); m8NA 63354 TAL1 leukemia 1
TRAF family
PREDICTED: Cams member-
CfaAfftc.15 familiariδ similar to TBAF associat interacting protein TANK ed 620,1.81 s tsatorm a (LOC608032); XM 8449 NFKB at ..99E-03 1.34E-02 f mftNA 96 TANK activator faniiliaris similar to TAO kinase 3; transcript
Cfa.20509, variant i (LOC477502); XM 8574
1.81 s at 3.S2E-03 1.63E-02 0.7 mRNA 80 TAOK3 TAP kinase 3
80s taurus thrβonyi-WNA
CfaAffr.28 synthetase; mRNA (cONA done MGC: *2St47 814.1.S1 s 1MAGE:79S<»J99>; threonyl-tRNA at i.iie-03 1.2OE-O2 0,75 complete cds BC103082 TARS synthetase
PRfOICTFD. Cams fβmillarts similar to
Cfa.2625.1 tfcreonyMRNA syn*«tase XM 5365 threonyl-tRNA
,A1 at 2.226-02 3.31E-O2 0.72 (LOC479370); mRNA 09 TARS synthetase
264 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000266_0001
265 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
T-cell immune
PREDICTED: Cams regulator 1. famillarts similar to T-eefi; ATPase, H+ immune regulator 1 transportinq, teoform a; transcript
Cfa.11351. variant 1 (LOC483691); XM 5408 lysosomal VO
1.A1 at I.S9E-02 3.06E-02 0.74 mRNA 12 TCIRG 1 subunit A3 familiaris similar to T- comptex j>-oteiκ i; alpha subunit (TCfM-aSpha; (CCT-βipha); transcript
Cfa.21272. variant 6 (LOC484064): XM 8576
1.81 s at 6.966-04 1.07E-O2 0.74 mRNA 32 TCP1 t-comp)ex 1 faniiliarts similar to T- βmptex protein I; alpha subunit (TCP-1-aipha) (CCT-aipha); transcfipt
Cfa.970.1. variant S (LOC4S40S4); XM 8576 S1 s at 473e-0<* 9.95E-O3 0.72 mWA 83 TCP1 t-comp)ex 1 t-complex- associated- teslis-
Cfa.217.1, Caπls fdinilisrts TCT61L expressed 1- S1 s at 2.2SE-02 3.30E-O2 0.76fmRNA; complete 08s AF491301 TCTE1L like
PREDICTED. Cams famillarts similar to Telomere repeat bintJrtg telomeric factor 2 interact!!*! repeat binding protein 1 (TRF3- interacting telαmertc factor 2,
Cfe.10296. proCeiπ Rspl) (hR3pJ> XM 5367 interacting
1-A1 at 4.96E-0S 7.92E-03 0.76 (LOC479643), mRMA 76
PREDICTED: Csnls faniiliaris similar to Testin testis derived
Cfe.11744. (TεsS); transcript variant XM S608 transcript (3
1.A1 s at I.S8E-03 1.28E-02 O.73J5 (LOC475293); mRNA 64 TES LlM domains)
PREDICTED: Cams famillarts similar to Transcrιρt»n factor A: mitochondrial precufsar (mtTFA) (Mltochondrl-I
CfaAffx.19 ! trsnswiption factor 1) (MtTFJ) (Transcription transcription 117.1.S1 ai factor 6-lιke 2) XM 5461 factor A, t I.74E-03 1.306-02 0.6S (UX4SS989); mRMA 07 TFAM mitochondrial familiaris similar to transcription factor K tsoform a; transcnpt
Cfa.1175.1 variant I (IOWS292); XM 5325 transcription
,A1 s at 3.036-02 3.87E-O2 0.7_ mSNA 23 TFEC factor EC
TlA 1 cytotoxic
PREDICTED: Cams granule- familiaris sim'tar to TIAl associat protein isoform 2, ed
Cfa.18602. transcript variant 1 XM 8478 RNA bindinp
2.S1 s at 2J9£-02 3A2HOΪ 0.6V (.OC$IU62S); mRMA 49 T1A1 protein
266 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
tyrosine
PREDICTED- Cants kinase with famiiiβris similar to immunoαlobυli tyrosine (unase wiΦ n-lik ιmmuπoglot>u(tn-(tk« and e and
Cfa.5301.1 EGF-like domains 1 XM 5396 £GF-)ike
.S1 at ..ssε-04 9.006-03 1.34 (LOC4S2535); mRMA 52 TIE1 domains 1 translocasβ of
PREDICTED: Canls familiaris similar to inner Mitochondria! import lrcnei mitochondrial membrane transiocsse suburtlt Tιm23; transcript membrane 23
Cfa.17788. variant 2 (LOC48S776): XM 8508 homoloq
1.81 at 1.486-03 1.25E-O2 0.75 mRNA 59 T1MM23 (yeast)
TCDD-
Homo sapiens mRMA; inducible
CteAffx.14 I cONA DKPZB686N03S1 POIv(ADP- (from done 014.1. S1 ai DKF2p68$NQ351); ribose) t i β.ese-oj •M9E-O2 0.74 complete cds BX537965 TlPARP polymerase rKcCTKrrcL' Λ-βϊtis fanύliβris similar to talin
Cfe.12147. 1; transcript variant £5 XM 8616 1.A1 s at 5,S8E-02 S.41E-02 .35 (UX474759), mRMA 40 TLN 1 talin 1
CfaAffr.60 earns iupus ramntarts TtR4 mRNA for Toll-like 1.1.S1 β a receptor 4 protejn; toll-like t i.iie-02 2.40E-02 0,75 complete cds AB080383 TLR4 receptor 4
PftEDICTED: Cams fβmillarts similar to B8P-
Cfa.10886. like protein 2 Ssoform a XM 5361 TM 2 domain
1.A1 s at U66-03 X.23E-O2 0.77 (IOC479O2O); mRNA 73 TM2D3 containino 3 fatniliari? similar to Transrtiembrane 9 transmembran
CfeAflx.13 superfamily protein membe.' i precursor,
912.1.81 s transσipt variant 3 XM 8546 superfamily at 3.91E-04 9.61E-03 0.72J(LOC6S27SS); mRMA 99 TM9SF3 member 3 familiaris similar to Transιr»eiiibιvane 9 transmembran
CfaAHx.13 superfamily protein member 3 precursor; e 9.
■ 1.S1 S transcript variant 3 XM 8546 superfamily at 4.70E-04 9.S36-03 0.74 (LOC6S2786); mRMA 99 TM9SF3 member 3 fβmillarts similar to Transmembrane 9 transmembran
CfaAffx.13 superfamily protein member 3 precursor; ■ 1.S1 s transcript variant S XM S547 superfamily at 9.8SE-06 6.68E-03 0.71; (.0C$iϋ7ϊ»); mRMA 62 TM9SF3 member 3
PR6D1CTED-. Canls
CfaAffx,20 familiaris similar to trans putative membrane membran 818.1.S1 S protein (IOC478992); XM 5496 e and coiled- at 3,2tε-02 3.99E-02 0.74 mRNA 26 TMCOI coil domains 1
PREDICTED; Cams transmembran familiaris similar to e emp24-like
CfaAf6t,26 transmembtane traffScXinj trafficking protein 21; transcript 060.1.S1 s variant 1 (LOC610559); XM 8489 protein 10 at 2.34E-03 1.40E-02 0.73 mRNA 50 TMED10 (yeast)
267 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
transmembran
PREDICTED- Cants e emρ24 famiiiβris similar to protein Transmembrane eτnρ24 transport domain containing protein
Cfa.1771β. 5 precursor (LOC479947); XM 5370 domain
1.S1 s at ..38E-02 2.666-02 '2 rnftNA 72 TMED5 containing 5 transmembran
PREOlCTED. Pan e emp24 troglodytes toll-like firotein receptor adaptor transport motecute 2; transcript
Cfa.2058.1 variant 2 (TICAM2); XM 0011 ,A1 at 8.536-04 1.13E-O2 0.74 mRNA 47606 TMED7 containing 7
PREDICTED: tarts familiaris nypotrtetscai
CfaAffec.77 profcsn IQC608427 XM 8454 TMEM1 transmembran 21.1. SI at -.796-04 9,0OE-OJ 0.54 (LOG6Q8427J; mRNA 53 26A e protein 126A
CfaAffx.24 FKcDiCTcijrcanis famiiiβris hypothetical 003.1.S1 s IOC4790M XM 5362 TMEM 1 transmembran st 2.0SE-04 9.06E-03 0.70 (U5C479094), mRMA 28 e protein 128
PREDiCTETjrcans famillaris similar to TPA
Cia.10592. regulated locus XM 5323 TMEM1 transmembran 1.A1 S at i.iae-02 2,40E»02 1.77 (LOC475144); mRNA 75 65 e protein 165
CKtUItItU. UtfliS familiails similar to
Cfa.10458, CG14199-PA XM 8474 TMEM1 transmembran 1.81 at ..31E-03 1.23E-O2 0.76 (LOC6S0083); mRNA 81 67A e protein 167A
CfaAffx.10 i PRcDICTfcO; CSfiis famiiiBris HypotftetJeai 660.1.S1 a! LOC130733 XM 5329 TMEM 1 transmembran t ! S.09E-02 6.67E-02 .36 (UX475737); mRMA 44 78 e protein 178 ftimiliaris sitiiilar to CG12765-PA; trarsscript
Cfa.1619.1 variβnt 3 (LOC47SSS4); XM 8506 TMEM 1 transmembran
,S1 s at I.62E-02 2.8S6-02 0.76 mRNA 17 83A e protein 163A familiaris sifi«lar Io H5PC171 μfotein;
Cfa.6676.1 trsnswipt variant 1 XM 5468 TMEM2 transmembran
,S1 s at 2.26E-03 1.386-02 0.75 (LOC489761), mRI^A 81 08 e protein 208
CfaAffeUΘ familians similar to transmembrarie protein
43.1.S1 s 3QA; transcftpt vβriβm 4 XM 8623 TMEM3 transmembran at I.01E-02 2.3tE-O2 0.73 (LOC474973); mRMA 82 OA e protein 30A
Bos taurus cONA done
Cfa.838.2. IMAG6-8169S0S; with TMEM3 transmembran A1 at 6.22E-04 1.05E-O2 0.71! spparertt retained Iπtron BC114131 3 e protein 33 ttansmembra(i« protein 41B; mRNA (cDNA clone MGC: 143027
Cfe.1749,1 IMAGE:83OS4O2); TMEM4 transmembran
-A1 at 1.576-02 2.80E-02 0.75 comptete eds BC142213 1 B e protein 41 B
PREDICTED: Canls familiaris similar to
CfeAffx.14 Trarsmembrane protein SOS (Ha' p7- 419.1.81 s transreguleted protein 3) XM 5355 TMEM5 transmembran
4.3δe-oj 1.69E-02 0.76 (LOC478Λ0S); mRNA 82 OB e protein 5OB
268 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000270_0001
269 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000271_0001
270 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED: Carts famiHaiis similar to trafficking hematopoietic prot stem/progenitor cells ein
Cfa.15072. 176; transcript variant 2 XM 8449 TRAPP particle
2.S1 a at 5.546-03 1.82E-02 0.72 (LOC47%14); mRNA 29 C2L complex 2-like
PREDICTED: Canis TP53
CfaAffx.87 familiaris similar to pS3- regulated induciSie ceil-survival 0.1. S1 s a factor; transcnpt vβrisnt 1 XM 5463 inhibitor of t 3.S6E-03 1.S9E-02 0.75 (.00459217); mRNA 35 TRIAP1 apoptosis 1 familiaris similar to tripartite motrf<oπtainin§ 39 isofbrm 2; transαipt
CfeABx.15 variant 2 (LOC481703); XM 8505 tripartite motif- 43. LSI at 2.496-05 7.55E-O3 1.33 mRNA 66 TR1M39 containino 39
PREDICTED: Cams TROVE famϋiaris similar to 6CkD
Cfa.17405. Ro/SSA auteanttgen XM 5361 TROVE domain family,
1,81 s at 9.21E-03 2,22E»O2 076 (LOC478957); mRNA 15 2 member 2 transient
Mus muscukts 12 days embryo eyebal! cDNA, receptor RIKEN fulf-leπgth potential enfictxd library; cation
CfaAffx,1Q I done:D230002019 chann prodwct transient receptoi el. 082.1.S1 ai protein 4; full insert subfamily C, t 2.386-03 1.44E-O2 1.33 sequence AK084139 Trpc4 member 4
PREDlCTED: Cams famiiisris similar to Ts translation Elongation factor Ts; mitochondrial precursor elongation
Cfa.10978. (EF-Ts) (EF-TSfIt) XM 5382 factor, 1.A1 at 3.576-03 1.59E-O2 0.72 (LOC-ISIlSt); mRNA 55 TSFM mitochondrial familiaris similar to
Cfe.832.1, transiin (LOC4S3876); XM 5409 S1 at 5,36C-O^ 1.02E-02 0.76 m»NA 96 TSN transiin nslin-
Scs taurυs traπsllrt-
Cfa.10562, dSSOCtøttϊu f^CtOf X NiM 0010 associated 1.31 at 1.936-03 1.33E-02 0,7 (TSNAX); mRNA 76006 TSNAX factor X
CfaAfftc.96 PKtDiCTtD: tanTs t familiaris similar to etratiicopepti
96.1.S1 S CS5290-?A (LOC475719): XM 5329 de repeat at 2.64E-04 9.11E-03 0.69 mRNA 27 TTC27 domain 27
CfaAffx.27 PKcLjrcTBTjrcsnis t familiaris hypofrietical etratricopepti 815.1.S1 s LOC4S0172 XM 5372 de repeat at 3.8SE-03 1.63E-02 0.76 (_OC430VΛi); mRMA 96 TTC39C domain 39C
PREDICreoTCanis t farmliarts hypothetical etratricopepti
CfaAffx,90 .OC148014 XM 5416 de repeat 12.1.S1 at 6.31E-04 1.05E-02 lJ7 (LOC484S03); mRNA 17 TTC9S domain 9B famiiieris similar to
Cfa.11081. UitMjJin; 8et3 S XM 5320 1.31 at S.14E-02 s.iae-02 0.74 (UX474330), mRMA 60 TUBB tubulin, beta tubulin,
PREDICTED; Canis gamma familiaris similar to tυbu)in; gamma compiex complex
Cfa.19230. associated protein 2 XM 5379 associated
1.S1 at 2.S1E-02 3.SOE-O2 0.75 (LOC480329), rc.RHA 46 protein 2
2?l Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PREDICTED- Cants Tu translation familiβriε sirraler to Tu transition eior>gation elongation
Cfa.10170, factor, mitocffoπdπsl XM 5369 factor,
1.A1 s at 7.34E-03 2.026-02 0.76 (LOC47θ796); mftNA 24 TUFM mitochondrial
PREDICTED: Canls famiiisris similar to Triioreβoxin domain containing protein 1 precursor
(Transmembrane Trx- related protein) thior (Trnoredoxin-nirtated edoxin
Cfa,3002,1 transmembrane protein) XM 8483 domain
.S1 at I.09E-03 1.20E-02 0.72 (LOCS10791); mRNA 39 containing 1
PREDICTED: Canis fiamtliaris similar to Thiαredoxin domain containing protein l precursor
(Transmembrane Trx-
CfeAfix.22 related μtotein) thior (Thioredoxin-related edoxin 542.1, S1 s transmembrane protβiri) XM 8483 TXNDC domain ι.9βε-(κ 9.06E-O3 0.73 (IOC6.079.); mRNA ainir
CfaAf{χ.1O familiaris similar to thior Oiioredoxln domain edoxin 33.1.S1 s containing 10 XM 5333 TXNDC
8.90€-04 l.HE-02 0.68 (IOC176176); mRNA 81 10 containino 10 rREDICTRUrcSfTS thior familiaris similar to edoxin αa.20679, disulfide isomerase XM 6473 TXNDC LSI at 5.05 E-03 1.76E-02 0.72 (LOC609963); mRNA 20 15 containing 15 familiaris simitar to Thioreaoion domain thioredoxin containing protein 4 domain precursor (Endoplasmic containing 4 reticulum resident protein
Cfa.19620, £ftp44) (LOC474781); XM 5320 TXNDC (endoplasmic
1.S1 s at 1.126-03 1.20E-O2 0.74 mRNA 11 4 reticulum)
PREDICTCD: Cams familiaris similar to ATP thior binding protein associates edoxin
Cfa.19939. with cell diffiererrtiatioT XM 5317 domain LSI s at I.55E-04 9.00E-03 0.73 (LOC474557); mRNA 85 containing 9 familiaris similar to diml;
Cfa.11189, ttanscript variant 1 XM 5333 thioredoxin- 1.A1 at Ϊ.73E-04 9.00E-03 0.7SJ(LOC4761S6); mRNA 63 TXNL4A like 4A
CfaAf6t,98 PKcDICTEUrCaTW tatiύliaris similar to dimt; 7.LS1 s a transcript variant 1 XM 5333 thioredoxin- t 8JSE-0S 8.77E-03 0.75 (_OC47615δ); mRMA 63 TXNL4A like 4A
PREDICTED: Canls familiaris similar to Splicing factor υ2AF 35 kDa subunlt (U2 auidliary U2 small factor 35 kDa subumt) nucl RNA (U2 snRNP aυxSiary factor ear
Cfa.10736. small subunit) XM 5355 auxiliary factor
1.A1 s at S.48£-03 1.82E-02 0.73 (LOC478422); mRNA 9Θ U2AF1 1
272 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
faniiiiaris similar to U2 U2 small smafi nuclear RNA auxiliary factor 1-like 4; nuclear RNA
Cfa.11590, transcript variant 3 XM 8626 U2AF1L auxiliary factor
1.A1 at 2.76E-02 3.68E-02 0.77J(LOC4764δ0); mRNA 81 1-like 4
PREOICTED-. GmIs famiiieris similar to UDP-N acetylftexosamme UDP-N- p^ophospho^iase acteylqlucosa (Antigen X) (AGX) (Sperm associated antigen 2); mine
Cfa.2503.1 transcript variant 1 XM 5457 pyrophosphor
■S1 at 2.076-02 3.19E-O2 0.75 (UXHSS66O; mRNA 81 UAP1 ylase 1
PREDICTED: Canls famiiisris similar to UDP-N acetylhexosβtnine UDP-N- pyrσphσsptwylase acteylαlυcosa (Anttgen X) (AGX) (Sperm associated antigen 2); mine
Cfa.2503.1 transcript variant 1 XM 5457 pyrophosphor
,S1 s at i.osε-02 2.34E-02 0,77 (LOC488664); mRNA 81 UAP1 ylase 1 farmliaris simitar to ubiquitin-like ubiquitiii-activating enzyme ElC isoform 1; modifier
Cfa.1092,1 transcript variant 3 XM 8466 activating
,S1 at 4.22E-03 1.686-02 0.69 (UXT476560); mRMA 97 UBA3 en2vme 3 famιliari5 similar to ubiquitin-liKe ubtςuitin-activating enzv>«e ElC Isofam 1; modifier
7711,51 S transcript variant 10 XM 8592 activating at 9.84£-04 1.16E-02 0.7 {10O176S60); mRNA 48 USA3 enzyme 3 fβmiliarts similar to ubiquitin-likβ
CfaAffx.10 i ubiquitln-artivating eru^Tne El-domain modifier 573.1. S1 ai containing i isoform ! XM 5427 activating t S..2ε-(M i.oiε-02 0.74 (LOC485664); mRhU 84 UBA5 enzyme 5 fβmillarts similar to Ubiqυitjn-conjυgatjng ubiquitin- (MiX)We E2 A {Ubtøuifctv coniugatino.
CfaAfftt,26 I protein iigase A) {Ubiquiϋn carrier protsin en2vme E2A 164.1.Si έ A) (HR6A) (mHR6A) XM S492 (RAD6
L 7.47E-0S 8.S76-03 0.72 (LOC492095), mRMA H UBE2A homolog) familiaris similar to Ubquitiπ-conjugatiπg ubiαuitin- en2yme E2 61 (Ubtciufcn- coniuαatinq protein iigase El) enzyme E2E 1
CfaAffit,96 (Ublqultin earner protetn El) (UbCMi); transcript (UBC4/5 18.1.S1 s variant 1 (LOC47704a); XM 5342 homoloq, at 4.17E-03 1.676-02 7 mRNA 45 UB£2E1 yeast) famillarts similar to Ubiquitin-eonjucsating enzyme E2 E3 (Uβlquitln- pititein ilgase E3) ubiquitin- (Ubiςυiftn carrier protan conjugatinςi £3) (Ubiquitin-conjugatinc; enzyme E2E 3 eny.ymβ E7.-23 kθa) (UbcM2); transαspt (USC4/5
Cfa.457.1. vartart 2 (LOC612823); XM 8574 homoloα . S1 s at 7.316-03 2.01E-O2 0.71: mSNA 08 UBE2E3 yeast)
273 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Mfeiguitin- coniuqatino
PREDICTED: Cams enzyme E2G familiaris similar to 2 (UBC7 ubiquitin-conjugating
Cfa.11340. enzyme E2G 2 XM 5356 homolofl, 1.S1 at 2.246-04 9.066-03 75 (L0C6SSSS1); mftNA 03 UBE2G2 yeast) ubiquitin- coniugating enzyme Eg1
PREDICTED: Pen J1 (UBC6 troglodytes ubiquitsn-
CfaAfftc.55 coπjugating enzyme E2; XM 5186 homoloq, 94.1.S1 at i.ooe-03 1.17E-O2 O.φl (UBRM); mRNA 36 U8E2J1 yeast) ubiquitin-
PREDICTED: Canis conjuqatinq familiaris simitar to enzyme E2,
CfaAffx.SS ubiquitift-cofyugstinς erβyme E2; Jl; tt'βnserlpt J1 (UBC6
95. LSI s vβrβnt 1 (LOC474S93); XM 5322 homoloq. fit 2,08£-04 9.06E-03 O.δδ mRNA 30 UBE2J1 veast) ubiquitin-
PREDICTED: Cams conjuqatinQ familiariδ similar to enzyme E2K
CfeAffec.24 huntiπgbr interacting (UBC 1 proton 2; transciipt 469.1, S1 S variant 1 (LOC60SS31); XM 8460 homoloq, at 7.776-03 2.06E-O2 0.69 mRNA 94 UBE2K veast) famillarts similar to UbiqυiSn-coniυgaSng enx>iϊ!e 62 13 (Ubiquitirt- protein iigase L3) (Ubiqυrtin carrier protatn ubiαuitin- 13) (UbCt-M); transcript
Cfa.11980, variant 1 (LOC477572); XM 5347 conjugating
1.A1 s at 1.62E-03 1.27E-02 0.77 mftNA 67 UBE2L3 enzyme E2L 3 familiaris similar to ubiςuitin conjugating ubiquitin- enrvme E2L 6; trsoscipt
Cfa.17038, variant 1 (LOC47S967): XM 5331 coniuqatinq 1.S1 at 2.4δε-02 3.47E-O2 0.7*? mRNA 74 UBE2L6 enzyme E2L 6
PftEDICTεO: Cams ubiquilin- farmliaris similar to conjuqatinq ubiquitin-conjugating
Cfe.11552. enzyme E2 variant i XM 5344 enzyme E2
1,81 a at 1.48E-03 1,2SE»O2 0.7S (LOC477262); mRNA 54 UBE2V1 variant 1 familiaris similar to ubiςuitin protein llgass ubiαuitin E3A isofbrm 3; transcript
Cfa.620.2. variant Z (LOC479010); XM 6431 protein ligase S1 s at i.26ε-03 1.236-02 0.73 mftNA 47 UBE3A E3A familiaris similar to ubiquitin protein figβse ubiquitin BA isoform 3; transcript
Cfa.β20.1. variant S (LOC4790X0); XM 8506 protein ligase A1 s at 3.0βε-03 J.63E-O2 0.74 mRNA 86 UBE3A E3A ubiguitination factor E4A
Homo sapiens mRNA for (UFD2
Cfa.9635.1 KJAA01Ϊ6 gene; partial homolop,
.A1 at 3.92E-03 1.64E-02 0.77 CdS D50916 UBE4A veast)
274 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Cfa,9708,1 Homo sapierss ubιqu*ιv NM 0071
■A1 at I.O5E-03 1.196-02 O.75jlike -1 (UBU); mRNA 06 UBL3 ubiquitin-like 3
PREDICTED: Canis ubiQuitin-like famiiieris similar to ubtcjuitin-iike domain containing
CfaAHx.26 containing CTD phosphatase 1; transcript CTD 450.1. S1 s variant 1 (LOC4S9I53); XM 5462 phosphatase at 2.526-03 1.43E-O2 0.7<? mWA 71 UBLCP1 1
PREDICTED: Cartis Wbiqujtin-likβ fβmiliaris similar to ubiquitin-fike domain containing containing CTD CTD phosphatase I; transcript
Cfe.18325. variant 2 (LOO489153); XM 8620 phosphatase
1.S1 at 1..8E-03 1.23E-02 0.74 mRNA 92 UBLCP1 1 fβmillarts similar to ubiquilin 1 isoform 1;
Cfa.3288.1 transcnpt variant 0 XM 8532 UBQLN
.S1 s at 3.8SE-03 l,63E»02 0.72 (LOC476312); rxRNA 08 1 upjquiiin 1 famlllarts similar to ubiquilirs 1 Isoform i,
Cla.3289.2 transcript variant 0 XM 8532 UBQLN
,S1 s at 9.836-03 2.29E-O2 0.71 (LOC476312); rxRNA 08 1 ubiQuiiin 1
PREDICTED: Canis fanύliβris similar to Rep-S protein (Reproduction 3
Cfa.8225.1 protein) (D8S2298E) XM 5494 UBX domain
■A1 s at 5.27E-0S 7.92E-03 0.76 (LOC475595), mRMA 49 UBXN8 protein 8
PREDICTED: Canls ubiquitin famiiisris similar to carboxyl- utiicjuitin C-terminal
Cfa.1152,1 hydrolase UCH 37 XM 5361 terminal
,A1 s at 9,84E-06 6.68E-03 0.69 (LOC47S958); mRNA 16 UCHL5 hydrolase L5 uncoupling protein 2
CfaAffx.92 Canis lupus familiarts ( uq>2 mRNA for mitochondrial 91.1.S1 s unc<κipl)ng protein 2; . proton at 2.63E-02 3.S9E-02 .3S compete c<ls AB020887 UCP2 carrier)
CfaAffx,99 PREDICTEDT CaniS familiaπs similar to 99.1.S1 S ubiquitiii-fold modlte 1 XM 5344 ubiquitin-fold at 2.64E-03 l,4SE»02 1.76 (LOC477297); mRNA 89 UFMI modifier 1 familiariδ similar to UDP- glucose pyroprtosphoryiase 2 UDPncilucos tsoform a; transcript e
Cfa.20677. variant 2 (IOC47461S),: XM 8608 pyrophosphor
2.S1 s at s.2βe-04 1.01 £-02 0.73 mSMA UGP2 ylase 2 familiaris similβr to UDP- glucose
CfaAffic,56 pyrophosphoryia5e 2 lsatorm a; transcript UDP-glucose 56.1.51 s variant 2 (LOC47461S); XM 8608 pyroohosphor at 2.47€-05 7.55E-O3 0.67 mRNA 50 UGP2 ylase 2
275 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000277_0001
276 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famillarts similar to Ubiςurtin cartxwyl- teiinlnal hydrolase i (Ubiqυrtin thiotestsrase 1) (Ubiquibn-specffsc processing protease 1) (De»ib(quitmating enzyme ubiquitin l,ι (hUBP); transcript
Cfa.19994. variant I (IOW9S49),: XM 5366 specific
1.81 s at i.sie-04 9.00E-O3 0.69 mSMA 88 USP1 peptidase 1 fβmiliaris similar to Ubiquitin carboxyt- terminal hydrolase i (Ubiquitin tfnotøsterase 1) {Ubiquitin-specific processing protease 1)
CfaAffx,26 I (Deυbiqυmnsδng enzyme ubiquitin 1) (hUBP); transcript 718.1.81 ai variant 1 (LOC479549); XM 5366 specific t ϊ,27E-02 2.54E-02 OJS mRNA 88 USPI peptidase 1 ramiliβris similar to ubiquitin ubiςuitiri-speαfic protease
Cfa-19562. 12-Kke 1 (IOC486033); XM 5431 specific
1.S1 at 4.136-04 9.686-03 O.βS mRNA 59 USP12 peptidase 12
CjaAffit.11 I ramiliβris similar to ubiαuitin ubιςu*rι-speαfιc protease 142.1. S 1 ai 12-Kte I (U0C486033); specific t 3.20E-03 1.S4E-02 0.75 mftNA 59 USP12 peptidase 12
UTP3. small subunit (SSU) processome
PR6O1CTΪD: Canls co familiariδ similar to mponent.
Cfa.2506.1 disrupter of siieoαπς 10 XM 5323 homoloq (S.
,S1 s at 1.S3E-02 2.776-02 0.7S (LOC47S167); mRNA 99 UTP3 cerevisiae)
Cfa.4554,1 Canis familiars utrophin .S1 s at B.7SE-03 2.186-02 0.77 mRNA; complete Kis AY095485 UTRN utrophin
Homo saeiers vesicle- associated membrane associated protein 7 (VAMP7); αa.1744.1 transαipt variant 1; NM 0056 membrane Al at S.0fJt-04 1.00E-02 0.7S mRNA 38 VAMP7 protein 7
Homo sapiens vav 3 vav 3 guanine guanine nucleotide nucl exchange factor (VAV3); eotide
Cfa.2698.1 transαipt variant I; NM 0061 exchange ,A1 at 4.06E-03 1.65E-02 0,75 mRNA 13 VAV3 factor
PREDiαED: Canis familiaris similar to Volt«ige-Oepenrient arioiv selective chβnnei protein 1 (VDAC-I) (hVDACt) (Outer mttechαrttJnat membrane ptoteln poiin voll 1) (Piasmaleromal porln) d (Porin 31Ht) (PofSn ependent
Cfa.1590,2 31HM) (LOC474681); XM 5319 anion channel
-S1 s at 3..26-(M 9.28E-03 0.74 rnRNA 07 VDAC 1 1
277 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famiiiBrts similar to voltage-
CfaAffx,23 vol»ge-<iepen<tent anion d channel 2; transcript ependent 653,1, S1 S variant 2 (LOC479255); XM 8466 anion channel at 3.53E-03 1.59E-02 OJS rnRNA 49 VDAC2
Canis familiars von Hppei Lindau disease tumor von Hippel-
Cfa.16229, suppre&sof (VML) mftNA; Lindau tumor
LSI at 4.42E-04 9.78E-03 OJS complete cds AY764285 VHL suppressor
PREDICTED. Cams vacuolar famϋlarts similar to protein sorting vacuoiar protein sotting
Cfa.818.1, 13A isofarm A XM 5335 13 homolOQ A A1 s at 7.73E-03 2.06E-02 0,7 (LOC476319); mRNA 22 VPS 13A (S, cerevisiae)
PREDICTED: Cams familiaris similar to vacuolar
CfeAffx,13 Vacuolar protein sorting 29 (Veside protein sotting protein sorting 436.1, S1 S 29); transcript variant 2 XM 8564 29 homolofl at I.36E-03 1.23E-02 0.73 (10O177W); mRNA 90 VPS29 (S. cerevisiae)
Bos taurus vAcixjLai protein sorting 3S riomolog (S. cetevisiae); vacuolar mftNA (cONA ctone prot HGC: 128544 ein sorting
Cfa.13099. tMAGE:798S129); 35 homolog
1,81 S at 1J8E-03 1.30E-02 0.7S comptete cds BC105430 VPS35 (S, cerevisiae)
PREDICtED: Canis vacuolar familiarts similar to vacuoiβr protelfi sotting protein sorting
Cfa.9366.1 3S; tfimscnpt variant i XM 5325 35 homoloα
■A1 at 5.436-04 1.02E-O2 0.68 {LOC47S3*>6); mRNA 70 VPS3S (S, cerevisiae)
PREDICTED: Canls vacuolar famιliari5 similar to prot vacuolar protein sorting ein sorting αa.9366.1 35; tronscfipt variant 2 XM 8539 35 homoloq.
.A1 s at 9,%E-03 2.30E-O2 0.73 (LOC47S346); mRMA 13 VPS35 (S. cerevisiae)
PREDICTED. Cams famillaris similar to vacuolar vacuoiβr proteifi sotting protein sorting factor 48; transσlpt
CfaAffx,1O variant 8 (LOC607306): XM 8522 4 homoloo B 79.1.S1 at i.6Sε-03 1.28E-O2 0.71 mRNA 73 VPS4B (S, cerevisiae)
CfaAf?x,27 PRtuiL I tLi: tanis famillaris similar to vaccinia 241.1. S1 s vaccinia related kinase I XM 5479 related kinase at 2.63E-02 3.59E-02 0.77 (LOC-JSOS^S); mRNA 70 VRK1 1
CfeAf{χ,24 familisris similar to wings apart- KIAA0261; tanscrtpt 486,1, S1 S variant 2 (LOC612S54); XM 8597 like homoloq at 2.36E-D4 9.06E-03 OJIi mRNA 25 WAPAL (Drosophila)
278 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
fsmillarts similar to Ttγptophanyi-tRNA syntfceBse (Tryptophan-
CfaAffx.27 tfiNA ligase) (TrpRS) trvptophanyl- (JFPS3) (bWRS); 418.1.S1 S transcript variant 1 XM 5375 tRNA
..246-02 2.52E-O2 1S (LOC480435); mRNA 54 WARS synthetase troglodytes WD nepeaS- containing protein l;
Cfa.14685. transcript variant I XM 001 1 WD repeat
1.A1 at i.lOE-02 2.39E-02 0.75 (WDRl); mRNA 58182 WDR 1 domain 1
PREDICTED: Canis. famillarts similar to WD repeal domain 20 isofwm
Cfa.10473, 2; transcript variant 6 XM 8635 WD repeat 1.S1 s at 5.966-03 1.87E-O2 0.7S (UOC6U234); mRNA 05 WDR20 domain 20 familiaris similar to WD
Cfa.8901.1 repeat domain 36 XM 5459 WD repeat ■A1 s at 6.94E-03 1.98E-02 072 (_OC483g?5); mRNA 92 WDR36 domain 36
CfaAffr.11 i FREDICTEoTCanis farmliaris similar to WD 948-1.S1 ai repeat ciomain 36 XM 5459 WD repeat t ! 2.50ε-03 1.42E-02 0,76 (LOC488S75); mRNA 92 WDR36 domain 36 famillaris similar to WD repeat domain 48;
Cfa.2333,1 transσipt variant 8 XM 8550 WD repeat
,S1 a at 2.9Sε-02 3.81E-02 0.71: (IOC477O27); mRNA 10 WDR48 domain 48 tioglodytes VVD repeat domain SlB; transcript
Cfa.1553.1 variant 4 (WDR51B); XM 0011 R51 WD repeat ■A1 at 2.30€-03 1.39E-O2 0.73 mRNA 66217 is I domain 51 B
CfaAffx.26 i PREDICTED: usn familiariδ similar to 528.1. S 1 ai CSSS43-PA (LOC469225;; XM 5463 WD repeat t i 2.86E-03 1.48E-02 0.76 mRNA 43 WDR70 domain 70 famillaris similar to WD
Cfa.17135. repeat ciomain 75 XM 5455 WD repeat 1.81 s at 2.8S6-03 1.48E-O2 0.76 (LOC488443); mRNA 65 WDR75 domain 75
PREDICTED: Cams WD repeats famtliaπs similar to WD and SOF1 repeats and SOfI domain
Cfa.15346. containing {100175065); XM 5322 WDSOF domain
1.A1 s at 7,21E-OS 8.S2E-03 0.64 rnBNA 99 1 containing
WD repeat,
PREDICTED: Cams sterile alpha famillarts similar to WD repeat; SAM and U-box motif and U-
Cfa.847.1, domain containing 1 XM 5359 WDSUB box domain S1 s at i.nε-02 2.39E-02 0.75 (LOC478761); mRNA 26 1 containing 1
PREDICTED: Canls WD repeat familiaris similar to WD40 domain, repeat p--oteiιi Interacting with p^osplvotnosιti<les of phosphoinositi
Cfa.4588.1 49kDa (LOC490899); XM 5480 de interacting
-A1 at 1.7ie-02 2.92E-0. 0.76 mRNA 1 wingless-type
PRεOlCTΪD: Canls MMTV
CfaAffx,20 I familisriδ similar to Wnt- integration sit 9b protein precursor (Wnt e 766,1, S1 ai 15) (Wnt-ltb) XM 5480 family, t I.40ε-02 2.67E-02 1.33 (LOC490919); mRMA 42 WNT9B member 9B
279 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000281_0001
280 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
famiiiBrts similar to spJicirxj factor YXSZl-B isofbrm 2; transcript
Cfa.18982, variant 5 (LOC475161); XM 8563 YTH domain
LSI s at Ϊ.33E-02 2.60E-02 OJS ITlRNA 34 containing 1 tyrosine 3- monooxygena se/tryptophan
PREDICTED: Canis familiaris similar to W-3-3 protein epsilon (14-3-3E) monooxygena (Mitochondrial import se activation stimulation factor I protein, subunft) (MSF L);
Cfa-4461.1 transcript variant 3 XM 8633 epsilon
.S1 at I.28£-03 1.23E-02 0.7* (LOC480645); mftNA 28 YWHAE polypeptide tyrosine 3- monooxyαena se/trvptophan
PREDICTED: Cams & famlllarls similar to £4-3-3 monooxygena
CfaAlix.19 protein theta (t4-3-3 s protein tau); transcript e activation 065.1.S1 s vsriatΛ t (LOC607060); XM 5328 protein, theta at 3.49E-02 -U8E-02 0.71! wRNA 71 YWHAQ polypeptide tyrosine 3- monooxygena se/trvptophan
PR6D1CTED-. Canls Sz faniiliaris similar to 14-3-3 monooxyaena protein ttiete <i4-3-3 s protein tau); transcript e activation
CfaAfix.βO variant 3 (LOC607060); XM 851 1 protein, theta 10.1. SI at i.57£-03 1,26E-Oi 0.74 mRNA 29 YWHAQ polypeptide tyrosine 3- monooxyqena
PREDICTED.' Cβrtis famillaris similar to se/trvptophan tyrosine 3/t'γptophan 5 & monooxygenase monooxygena αaAfix.95 activation protein; zeta s polypeptide; transαipt e activation 31.1.S1 s vsriatΛ 2 (LOC475864); XM 8439 protein, zeta at I.2SE-03 1.23E-O2 0.74 mRNA 51 YWHA2 polypeptide cams lupus rati>ιι<art& zinc zinc fing finger; BGO-type er,
Cfe.1579.1 containing 5 (2BEOS); NM 0010 BED-tvpe
■A1 at 2.696-03 1.46E-O2 0.66 mRNA 97982 2BED5 containing 5 farmϋarts similar to »nc finger arxt BTB domain containing 20; transcript zinc finger and
Cfa.5314.1 variant 2 (LOC487987); XM 8434 BT8 domain ,A1 at 8.12E-03 2.ΪOE-O2 0.75 mRNA 45 ZSTB20 containing 20
C3ms iupus ramiiiaris zinc zinc finoer finger CCCH-typa
Cfa.21382. containing 15 (ZC3H15); NM 0011 CCCH-tvpe 1.S1 s at i.ssε-03 1.26E-0Z 0.71: mRNA 14605 ZC3H15 containing 15 famillaris similar to »nc
CfaAffx.28 finger: CCHC domain zinc fing containing 6; transcript er, 92. ISi s variant 8 (LOC476301); XM 8S10 CCHC domain
M 2.33E-03 l.396-0a 0.74 mRNA 73 containing 6 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
Figure imgf000283_0001
282 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
farwllails similar to ∑jnc finger FYVE domain- containing protein 16
CfaAfftc.13 ! (EmJofm) (Endosome- zinc finger, associated FYVE domain 975.1. S 1 ai protein) (IOC479167): XM 5363 ZFYVE1 FYVE domain
L 2.336-03 1.396-02 mRNA 10 6 containing 16 zinc metallopeptida
Pongo abeliS mftNA; cONA se (STE24
CfaAffx.54 DKFZ[tfS9I044S (from homoloq. S. 43.1.81 at L2iE-04 8.90E-03 0.76 done DKF2p45θtO445) CR860340 cerevisiae) zinc metallopeptida
Homo sapiens »nc s (STS2 nwtailopeptidase (STE24 e 4
Cfa,10β39. homotog; S. censvisiae) NM 0058 ZMPST homoioq, S.
1.A1 at I,6SC-03 1.29E-02 0.76 CZMPSTEM); mRNA 57 E24 cerevisiae)
PREDICTED: Cams familiariδ similar to Zinc finger HYND domain containing protein π
CfeAffx.84 (Adenovirus 5 ElA- zinc fincter, binding orotein) (SS65 58.1.S1 s protein); transcript varians XM 5352 ZMYND MYND domain at 9.09e-04 1.15E-O2 0,73 1 (LOC478023); mRNA 05 1 1 containing 11 famillarts similar to ZSnc
CfaAffx.11 finger protein 143 (SPH- biiKiing factoi); transcript 973.1.S1 s vβnsnt 3 (.00485384); XM 8587 zinc finger at 1.796-03 ι.3oε-oa 0.75 mRNA 81 ZNF143 protein 143
CfaAffx.45 KKtUIi. i tυ: cams fβmtϋaris similar to »nc 9.1.S1 s a finger protein IS XM 5366 zinc finger t 3.29€-03 1.S5E-0- 0.65 (LOC479S0S); mRNA 44 ZNF 18 protein 18 familiaris similar to zinc
Cfa.10986. finger orotein 207 XM S377 zinc finger 1.A1 s at i.OSE-03 1.176-02 0.76 α0C4βGδll), mRMA 11 ZNF207 protein 207 famillarts similar to ϊlne
Cfa.18401, finger protdn 207 XM 5377 zinc finoer 1.S1 s at s.nε-04 1.15E-O2 0.7<? (LOC48O6H); mRNA 31 ZNF207 protein 207 πwTio sapiens wπc Tiπger
Cfa.20746. protein 24 (ZNF24); NM 0069 zinc finger
1.S1 at 7.O4€-04 1.08E-O2 0.75 mm/κ protein 24 rκtxnκmxι: XΛI IUI
CfeAfix.20 familiaris similar to zinc finger p<oteln 2S9; .1,81 s transcript variant 2 XM 8452 zinc finger at s.ieε-03 1.79E-O2 0.77 {lOO»7S*2S); mRNA 19 ZNF259 protein 259 rKct7Krrcl77Λ-«ϊ}ls ftimiliaris similar to ZIIK
Cfa.1662.1 finger protein 292 XM 5390 zinc finger ,A1 at 3.26E-02 4.02E-02 076 (LOC481908), mRI^A 29 ZNF292 protein 292
PREDICTED: Canls familiaris similar to Zinc finger protein 330
Cfa-2298.1 (Nucleolar autoantig^-i XM 5332 zinc finger
.A1 at 2-99C-03 l.SlE-02 36) (LOC476073); mRNA 82 ZNF330 protein 330
283 Tabie 2:Genes Differentially Expressed in lymphocytes from Fa
PRK)ICTgD: Cβnls
CfaAffx,30 familisris similar to zinc finger protein 644 isσførm 924,1, S1 S 2; transcript vartartt 7 XM 8620 zinc finger at 9,%E-03 2.30E-02 OJS (LOC479957); mRNA 32 ZNF644 protein 644
CfaAf6t,12 i PKcDiCTtϋrcsπis familiaris similar to zinc 480.1.S1 ai finger protein 654 XM 5447 zinc finger t i 100E-02 2.30E-02 075 (UX437673); mRNA 97 ZNF654 protein 654
PREDICTED: Cams
CfaAHx.23 I famiiisris similar to zinc finger protein 655 isofoftn 026,1,51 ai c; banscript variant 2 XM 5469 zinc finger t s.nε-tκ 1Λ0E-O2 0.73 (LOC48985SJ; mRNA 73 ZNF655 protein 655
PREDICTED: Canis familiaris similar to Zinc finger pfotein 7 (Zlrte finger protein KOX-l) (Zinc
Cfa.1778,1 finger protein hF.iδ) XM 5323 zinc finger
.A1 s at 4.07E-03 1.6S6-02 0.76 (LOC47S129); mRMA 59 ZNF7 protein 7 famillarts similar to
Cfa.14593, HSPC038 protein XM 8439 zinc finoer
2.S1 a at 4.98E-03 1.76E-02 0,77 (LOC607_93); mRNA 18 ZNF706 protein 706
CfaAffx.35 familiaris similar to CG10979-PA; trarsicnpt
01.1 -S1 s variant S (LOC47S207): XM 8444 zinc finger at i.656-02 2.88E-O2 0.76 mRNA 14 2NF800 protein 800
CfaAffx.50 familiaris similar to zinc finger p<oteln 91 (HPf7; 53.1.S1 x HTFlO) (LQO!S-t326); 5414 zinc finger at 3.106-02 3.92E-O2 1.36 mRNA 42 2NF91 protein 91
PREDICTED-. Caπls famiiieris similar to Zinc finger HIT domain containing protein 1
Cfa.6304.1 (Cyciin G!-bindtfi9 protein XM 5368 zinc finger,
,A1 at e.soε-04 1.076-02 0.76(1, i (LOC479729); mRNA 55 ZNHiTI HIT type 1
PREDICTED. Pan zinc finger, ttoglodytes zinc fiιig«f; RAN-binding RAN-tnnd!ng domain
Cfa.9992,1 containing i protein XM 5080 domain
-A1 at 2.816-03 1.48E-O2 0.76 (2RAN61); mRMA 99 2RANB1 containing 1
PREDICTcD: Cams zinc finger,
CfaAffx,31 familiaris similar to Zinc RAN-bindinq finger protein 265 (Zinc 255.1.51 S finger; splicing) XM 5473 domain at 1.336-03 1.23E-02 0.7 (LOC490213); mRhU 34 ZRANB2 containing 2
PREDICTED: Cams ZW10, familiaris similar to kinetocnore
CfaAffr.21 Cenbomene/klnetochoie associat protssn zwlO homoiog; ed, 190.1.81 s transσipt variant 1 XM 5365 homolog at 3.49e-04 9.46E-03 0,77 (LOC4794i3); mRNA 69 ZW10 (Drosophila) familiarts similar to zwe
CfaAffx.31 finger: ZZ domain zinc fing containing 3; transcript er, ZZ- 203.1.S1 s variant 1 (LOC490203); XM 5473 type
4.13E-03 l.666-0a 0.76 mRNA 24 ;ontainino 3
284 Tabie 3: Key Genes associated with fatty acid metabolism in Fs
Probes identifying Key Genes in Adipose Tissue in fat and iean
Figure imgf000286_0001
285 Tabie 3: Key Genes associated with fatty acid metabolism in Fs
Probes identifying Key Genes in Lymphocytes from fat and Sean doc
Figure imgf000287_0001
286 Example 2
Determining the Effect of Various Substances or Ingredients on Gene Expression in Canine Cell Lines
{00259) Affymetriλ canine GeneChips* Canine- 1 and Canine- 2 were used (Canine- 2 replaced Canine- 1) to determine the effect of various test substances or ingredients such as MCTs: TΛGs: ALA; EPA; DRA; iinoleic acid (LA); Arachidonic Acid (.4.RA); stearic acid (SA), Myristic acid (MA), conjugated lirtoieic acid (CLA). GLA; arachidonic acid: lecithin; vitamin A, vitamin D, vitamin E, vitamin K, riboflavin, niacin, pyridoxins, pantothenic acid, folic acid, biotin vitamin C, catechiii, quercetin. theafiavin; ubiquinone; lycopene, lycoxanthin; resveratrol; α-!ipoic acid; L-carnitine; D-limonene; glucosamine; S- adenosylmethionine; chitosan, various materials containing one or more of these compounds, and s arious combination thereof on gene expression in four canine cell lines and appropriate controls. Each ingredient is tested in two concentrations as illustrated for selected sample ingredients shown in Table (>. The solvent at the higher of the two concentrations is used as a control. Four canine cell lines are used; CCL34 (kidney). CRL 1430 (thymus). CCL 183 (bone) (obtained from The American Tissue Culture Collection) and CTAC (thyroid) (See, Measurement of NK Activity in Effector Cells Purified from Canine Peripheral Lymphocytes, Veterinary Immunology and immunopathology. 35 ( 1993) 239-251). A cell line treated with an ingredient at a specific concentration is referred to as "treatment" and an untreated sample is referred to as "control." The words "genes" and "probes"' are used synonymously in this method. Gene expression is measured for the treatment cell lines and controls using the instructions provided with the Affymetrix chips.
(00260) A sample of the data obtained from these experiments is shown in Table 5. Table 5 shows the probe id, the p-\ alue. the fold change, the annotation of the top BLAST hit, the top BLAST hit accession number, the gene symbol and finally die gene description is given in the last column.
Based upon the physiological condition of the canines (a diagnosis as fat) and a comparison of the information from the Tables 1 , 2, 3 and 5, i,e, noting genes that are influenced by a test substance or ingredient and are also differentially expressed
287 in overweight canines compared to lean canines, a nutritional formula useful for selecting and preparing a food composition for overweight canines would be believed to contain one or more of the following ingredients in the following amounts (in vivo amounts in milligrams per kilogram of body weight per day (mg/kg day) are based upon extrapolation from amounts used in vitro, for example: DHA - from i to 30: EPA - from 1 to 30; EPA t)HA Combo (1.5: 1 ratio) - from 4/2 to 30/45; ALA - from 10 to KM); LA - from 30 to 600; ARA - from 5 to 50; SA - from 3 to 60 and MA - from 3 to 60. Based upon these data, a food composition and related diet containing one or more of these ingredients can be prepared and used to regulate the genes that are differentially expressed m overweight animals compared to lean animals. Such regulation will cause the modulation of the amount of adipose tissue on the animal and, therefore, in one embodiment, promote a shift to a desirable or normal (more lean) status and promote better health and wellness of the animal
Table 4: Ingredients Tested in Canine Cell Lines
Substance Concentration 1 Concentration 2 Solvent
DHA 0.005 mg ml (5 micro 0.025 mg-'ml (25 ETOH g ml) micro g. nil)
EPA 0.005 mg/ml (5 micro 0.025 mg ml (25 ETOH g/ml) micro g/ml)
EPA DHA 0.015 mg, mi EPA & 0.030 mg/ml EPA & ETOH Combo 1.5: 1 0.010 ma ml DHA 0.02 nig/ml DHA ratio (like in (total is 0.025 mg''ml) (total is 0.050 mg ml) fish oil) Alpha 0.05 mg/ml (50 micro 0.1 mg ml ( KK) micro ETOH linolenic acid g/ml) g/ml) (ALA) Linoleic acid 0.1 mg/ml ( 100 micro 0.5 mg/ml (500 micro ETOH (JLA) g/ml) g/ml)
Arachidonic 0.025 mg ml (25 0.05 mg/ml (50 micro ETOH acid (ARA) micro g/ml) g/ml) Stearic acid 0.01 mg/ml (10 micro 0.05 mg/ml (50 micro ETOH (SA) g/ml) g ml)
Myristic Acid 0.01 mg ml ( 10 micro 0.05 mg 'ml (50 micro ETOH (MA) g ml) g/ml)
Conjugated 0.02 mg/ml (20 0.1 mg/ml (100 micro MEOH Linoleic acid micro g/ml) g ml)
288 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
OHA in ETOH (CANINE-I); 5 records FC cutoff; 1.3; P- vaf cutofff: 0.05
^ Top Hit G«n«
Pmbe P-Vakιβ Change Top BLAST Annβt Accn. Symbol G«r» Desc,
PREDICTED-. Macaca mutetta carnitine XM 0011
1583403 at 4 (!8f W 1.S6 palmitoyltransferase IA (CPTlA); niRNA 01846 CPT1A IA
PREDICTED: Canis familiars Similar to [Pyruvate dehydrogenase [lipoamtde]] kinase isoϊym* 4; mitochondrial precursor pyruvate (Pyruvate dehydrogenase kinase lsoform XM 5394
1605486 at Z 36E-0J J.7700 1) (LOC482310): mRNA 27 PDK4 kinase isozyme 4
FKfcϋK- 1 tu: cams ramiwπs similar to Adipophitin (Adipose differentiation-related adiposg protein) (ADRP); transcript variant i XM 5319 d'ffereritiatjonrjslated
1585355 at 3 6SS-0? 1, 01 (LOC474720); m(WA 46 ADFP protein VKtUIl'TtDi'SmrfSmfiaπTsTmiTaflo
Adipophiiin (Adipose diffiβrentiation-retated protein) (ADRP); transcript variant 4 XM 8596 difforentiation-rcJatetf
1584851 at 4 COS-O? MK! (LOC^7-J720); mRNA 97 ADFP protein tty&'ϋiOISIλ tank famlflads similar Io angiopoietifi-like <5 protein (LQO47672"*); XM 5339
1591083 S 6650-1 2.9 mRNA 28 ANGPTL4 arxaiopoietin-iike 4
EPA Sn ETOH (CANINE-1); 8 records FC cutoff: 1 3; P- vai cutofff. 0.05
Figure imgf000290_0001
289 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000291_0001
290 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000292_0001
Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000293_0001
292 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000294_0001
293 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000295_0001
294 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000296_0001
295 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000297_0001
2% Tabie 5: Expression Profiling Results From Canine Ceii Lines in
PKtuiu fcu: c:ans rβrwians swvwar to Adipophlϋn (Adipose d!fferenttation-rel8teel ao!ιpom protein) (AORP); transcript variant S XM 5318 flifferentiatiorHaiated
1SB5355 at 3 3H-M 4.31 (LOW4720); mRNA 46 ADFP
PRεOtCTEO-. Canis faroiiiaris similar to [Pyuvate dehydrogenase [lipoamtde]) torβse isozyme <?; mitochondria) precursor pyruvate. (Pyruvate dehydrogenase kinase istrfoiri XM 5394 dehydrogenase
1605486 at / 6.SK-(H J a:U) (LOC482310); mRNA 27 PDK4 kinase isozvine 4
PREDICTED: Canis famiiiaris similar to Transforming growth fsctor-bets-inducitte oar Iy growth response protein 2 (TGFB- iπducibie early grmvth iβsponse protein 2) (TTEG-.) (KrueppeHite factor U) XM 5328
1604372 at 5 S8S-02 LOS (LOC475665); mRNA 73 KLF 11 KfUflpel.-liMfactor ii.
KKtυn. i fcø'. Lanis fβmiiians similar to Adipophiiin (Adipose differentiΛtioπ-tielated protein) (ADRP); transcript variant 4 XM 8596
1584951 at ^ 6JS: 01 1.2S (LOC474720); mRNA 97 ADFP protein
PKtUJC] fcϋ; Cane famiitaris similar to fragile X mental retarrfation 1; transcript XM 6616 fragile X πt&ntai
160S6Q8 at 3 WE-O- l.-Hvariaπt 12 (Fmrl): mRNA 51 FMR1 retardation 1
PREDICTED: canis fβmiitaris similar to ubiquitin-foid modifier i (L.OC477297); XM 5344 ubiqut-n-fold modifier
1584200 at 174r-i)7 A.M. mSfJA 89 UFM 1 1
PREDICTHD: Cβnis famllians carnitine palmitoyl transferase I isoform (CPTl); XM 5332 palmitoyltransferase
1582824 at 3 81S-O- mRNA 08 CPT1A lA iSiven
Stearic acid m ETOH <CANfi*JE-2); 47 records FC cutoff: 1.3; P-vai cutofff: 0.05
SsS1 S5? Top Hit Sβite
Probe P-Vakie Change Top BLAST Annot, Accn. Symbol G«rtβ Dβsc.
PREDiαeD; Mseaca mulatto DNA- DNA cross-link repasri crosslmk repair gene SNMt (DOREiA); XM 0010 1A (PSO? >x>moioq,
Cfe.15S48.lA1 at 4 MK-O- -2.:i8 mRNA 90942 DCLRE1A S. osrevisiae) hetøoaeneous
PREDICTED; Cane famiitaris sirnilβr to nuclsar heterogeneous nuclear ribonuctecprotein XM 5332 HNRNPU nbormoieoDrotflirt ϋ-
CfaAffx.24Q27.1.S1 at 303E-02 •ι.*9 U (LOC476053); mRNA 61 L2 like 2
Sus scrofs mRN.A; done:OVRMJ0088G09;
Cfe.12280,1.A1 at J.'.Br-i)? .U expfϊssed if ovaty AK235506
PREDICTED: Maαca mulatta carnitine XM 0011 palmitoyltransferase
Cfa.12S6,1.A1 at M/K-itf 'J palmitoyltransferase IA (CPTlA); mRNA 01846 CPT 1 A IA
PREDICTtD; Mβcaca rπulatta arπiiar to cell division cycle 42; transcript variant 4 XM 0011 LOC7076 simi|3r.!o..cell.drv.isign
Cfa.15508.2.S1 at :i (!9f -02 I..W (LOC707637); mRNA 00181 37 Sϊώ£^2
PREDICTED; Cane famiiiaris sirnilβr to heterogeneous nuclear ribonuctecprotein hGterooαneϋus A3; transcript variant 4 (IOC609295); XM 6591 LOC6092 nuetear
CfeAffx.292S4.1.S1 at 3 H Jt-Oi 1.% mRNA 93 95 f ibonucioopfoteirc A3
Homo sapiens forkhead box Pl (K)XPl); NM 0326
Cfa.16629.1.At at ).10f-0? !.S3 transcript variant l; mRNA 82 FOXP1 forkh^ad box PI
PKtUIt i to: Canis familians similar to feminization 1 homolog a; transαipt XM 5385 fem-1 homoloo c fC.
CfaAflx.1280.t.S1 at 3 355 02 •Invariant 1 (LOC481437); mRNA 57 FEM 1C giSflSrt§,> rlbosome binding
Canis famiiiaris mftNA for πbosome P/gMn 1 ^prnoiog
Cfa.3671.t.A1 s at 2.-10C 02 •1,34 receptor; piSO X87224 RRBP1 ■aOfrPa idog)
297 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000299_0001
298 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000300_0001
299 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000301_0001
300 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000302_0001
Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000303_0001
302 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000304_0001
Conjugate alpha-linoieic acid In MeOH (CANINE-2); 6 records FC cutoff: 1.3: P- vai cutofff; 0.05
Figure imgf000304_0002
303 Tabie 5: Expression Profiling Results From Canine Ceii Lines in
Figure imgf000305_0001
304 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000306_0001
305 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000307_0001
306 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000308_0001
307 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000309_0001
308 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
PREDICTED: Canis fsmitlaris simitar Co adenylosuccinate lyase;
Cfa.12520 transcript variant i XM 5317 adenviosucciπat
.1.A1 S at 1.64EO2! 4,46E-Oi t,4S (I.OC474499); mRNβ, 99,5 27 ADSL e lyase
PREDICTED: Canis fsmillaris similar to Adenylosuccinate synthetase 2 (IMP-- aspartate lipase 2)
Cfa.19535 (AtJSS 2) (AMPSβse 2) XM 5372 adenylosuccinat
.1.SI at 2.26E-02! 4.46E-01 1.38 (LOC480098); mRNA 92.6 20 ADSS e synthase
CfeAfix.16 Anophetes gamblae etc. PEST AGAP004931-PA
582.1.81 (AgaPJM3AP0O4931} XM 3150 AqaP AG AGAP004931- ϋ 1.6OE-O2! 4.46E-O* 0.72 mRNA; complete cds AP004931 PA
PxEDICTEO: CaπlS familiβπs similar to 1- acyl-sn-giyceroi-S- phosphate acyitraπsferase delta (1- i-acviqlvceroi-3- AGP acyftransferaso 4) phosphate Q- (1- AGPAT 4) (LysophosphatWk: add acyHransferase acyttf3n5ftw35βHd<Hta) 1 (LPAAT-deits) (l- (Ivsophosphatid αaAtrx,20 «ιcylg!yc«oi-3- phosphate O- ic acid
73. LSI a acyltransfβfase 4} XM 8500 acyitransferase. t 8.58E-O^i 4,saε-oi! 1.41 (LOC61Λ306); mRNA too AGPAT4
•wκzr?«~ιxr~mι~ trogi<xiyte5 allcytdinydftwyaαstone alkylglvcβfon phosphate synthase; e
Cfa.13638 transcript variant 3 XM 0011 phosphate
.1AI at 6.17E-02 4.51E-0 U (AGPS); mRNA 90 54211 AGPS synthase hydrocfliijon receptor; mRNA (cDNA done aryl MGC:37401
Cfe,19737 WA56:30342582); hydrocaιt>on .1.SI at 6.UE-D2! 4.SOE-Ol! 1. S3 compiete cds S4.8 BC070080 AHR receptor fsmillaris similar to
Cfa-2120, aftdtogerv-induced J XM 8493 androgen- 2.S1 at 3.SSE-O2 4,46E-OIi t,68 (LOC611677); mftNA 53.6 76 AJGI induced 1 familia.-is similar to fused toes homoiog:
Cfa.19796 transcfipt variant 1 XM 5353 AKT interacting
,1.S1 at 2.906-02! 4.46E-01! i.35 (LOC47S126); mRNA 02 protein famitiaris similar to aldehyde aldehyde d dehydrogenase 4Al ehydrogenase
Cfa.21376 precwsor (LOC612452!; XM 8501 4 family,
,1,S1 S at 7.08E-02! 4.54E-OIi 0.77 mRNA 97.9 79 ALDH4A1 member A1 familisns similar to aldehyde aldehyde dehydrogenase 4Al dehydrogenase
Cfa.2103β precursor (LOC612'SS2); XM 8501 4 family, .1.SI s atj 6.25E-02! 4,S0£-0l! i.43 mRNA 100 79 AIDH4A1 member A1 aldehyde
CfaAffx.14 PREDICTED: CsniS dehydrogenase famlliaris similar to 96.1.S1 s anttquΦπ (LOC4S1466); XM 5366 7 family, at - 50E-O2! 4.46E-01! I.4S mRNA 98.9 07 ALDH7A1 member A1
309 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000311_0001
3JO Tabte 8:Genes DiffeteπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000312_0001
3Jl Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000313_0001
3J2 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000314_0001
3J3 Tabte 8:Genes DiffeteπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000315_0001
3J4 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000316_0001
3Ϊ5 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000317_0001
3J6 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000318_0001
3Ϊ7 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000319_0001
3J8 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000320_0001
3J9 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000321_0001
320 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000322_0001
Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000323_0001
322 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000324_0001
323 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000325_0001
324 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000326_0001
325 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000327_0001
326 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000328_0001
327 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000329_0001
PREOlCTBD: Pan tfogiodytes cystewe-ridi cvsteine-rich hydrophobtc domain 2;
Cfa.447.1. transcript variant 2 XM 001 1 hydrophobic
51 at _.O0E*O2 4.46E-01 2 CH!C2 mRNA 64.1 45791 CH1C2 domain 2
Figure imgf000329_0002
328 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000330_0001
329 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000331_0001
330 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000332_0001
Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000333_0001
332 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000334_0001
333 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000335_0001
334 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000336_0001
335 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000337_0001
336 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000338_0001
337 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000339_0001
338 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000340_0001
339 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000341_0001
340 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
PREDICTED; Canis famitøris similar to ϋukaryotic translation initiation factor 3 subunit 2 (eIF-3 beta) eukarvotic (*IF3 p36) («IF3i) (TXtF translation bete receptor interacting
Cte.1038. protein I) (TRtP-X) XM 5353 initiation factor 1.S1 at 1006-01 4.6SE-01 £.56 (LOC4781S2); mRNA too E1F3I 3, subunit I famlliaris similar to βukaryotic
CfaAffx.20 Eutaryotic translation translation initiation factor 3 977.1.81 subunft 1 (eIF-3 alprta) XM 5446 initiation factor at 6.93E-O3 4.46E-OIi 1.36 (UX487532); mRNA 98.7 56 EIF3J 3. subunit J
PREDICTED: Cants fβmlliaris similar to Eukaryøtic translation initiation factor 4£ (eIM6) (eIP-4E) (inRMA eukarvotic cap^sinding protein) translation (elMF as køa sυfeυmt);
Cfa.1718. transcript variant 3 XM 6571 initiation factor 1.81 at 1.78E-02! 4.46E-01 1.48|(LOC487870); r»RNA 94.9 35 E1F4E 4E familians similar to eukarvotic
CfaAffx.27 eukaiyotic translation translation •nlttattoπ factor 5;
903.1.S1 transcript variant S XM 863S initiation factor s at 4.47E-02; 4,47E-OIi 1.34 (IOC480442); mftNA 100 19 E1F5 S
CfaAffx,30
Caπis familiaris
080.1.S1 neutrophil eiastase elastase 2, S at 3..6E-Q2! 4.46E-01 0.72 mRNA; eompiete cds 100 AF494190 neutrophil
PRεOJCrεO: Canis familiaris sittiilar to Zinc phosphodiesterase SLAC protein i (Ribonuctease 2 1) {RN9S« Z .) (tRNase Z 1) (tRNA 3 eretonuclease 1) (EIaC ttomoiog protein i) (Deleted in Ma29);
Cfa.14047 ti'Anscript variant 2 XM 8444 elaC homoiog 1
.1.A1 at 1.47E-O2 4.46E-OIi J.3S (IOC47S197); mRNA 70.1 00 ELAC 1 (E, coli)
PR601CTεD: Canis families similar to ETS- related transcription factor EJf-2 (£74-!ike E74-like factor factor 2) (New ETS- felated factor); 2 (ets domain
Cte.1872. transcript variant I XM 5332 transcription
1 S1 at 5.51E-O2! 4,SOE-Ol! 1.31 (LOC476080); mRNA 99.4
ELOVL family member 5, elongation of long chain fatty acids
CfaA-ffx.42 Poogo ab«lll rnftNA: cONA Dtσ2p469M0522 (FEN1/Elo2. 90.1.S1 s (from cione SUR4/£lo3-like.
8.32E-O2! 4.56E-OIi 1.32 DKFZp*69M0522) 82.9 CR8S7140 £LOVL5 yeast) Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000343_0001
342 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000344_0001
343 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000345_0001
344 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000346_0001
345 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000347_0001
346 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000348_0001
347 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000349_0001
348 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000350_0001
349 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000351_0001
350 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
aarnma-
CfaAffr.SS PREOTCTED- CaHe fsmiltaris BJrrUMwr to glutamyl 57.1.S1 a C4487.7 (LOC611603); XM 8492 cvclotransferas t 7.36E-O2 4.S4E-01! £.36 mRNA 99 8 84 GGCT
CfaAffrJB familiars similar to GTPasβ. IMAP GTPase; IMAP family 13.1.S1 a memwsr 7 XM 8484 family member
L 8.43E-02 4.SSE-01 £.43 (IOC610S9S); mRNA 39.2 SL GIMAP7 7 faroilfafis similar to G protdn-coupled receptor G protein- kmase-mbwactof 2 isofosm 1; transcript coupled
Cfa.1560. variant 1 (IOC477520); XM 5347 receptor kinase 1.A1 s at 6.05E-02; 4,soε-oii 0.76 mRNA 100 15 GIT2 interactor 2
PREDICTED: Canis fβmlϋaris similar to Qlvcosyltransfer giyeosyStrarsferase S
Cfa.15751 domain containing ϊ XM 5418 ase g domain .1.A1 at 8.72E-O2 4.59E-01! £.35 (LOC43473£); mftNA 100 47 GLT8D1 containing 1
CiaAffx,SB fsrnilians similar to germ g c cell-less protein: erm eil-less 92. LSI s transcript variant I XM 5385 homoloα 1
196E-O2 4.46E-01! £.49 (LOC481414); mRNA 98.3 M GMCL1 (Diosophila) famlliails simllai to germ p cell-less protein: erm cell-leβs
Cfa.1020, transcript variant I XM 5385 homoloα 1
J.92E-O2; 4,46E-Ol! 1.75 (LOC4814J4); mftNA 100 (Drosophila) yvιriξ)u«κ)enπi)ww;" tONA DK?2p4S9J£01 (ffom cione alia maturation.,
1.S1 at 3.96E-02! 4.46E-0.i IA DKF2R4S9J101) 49 CR860440 GMFB factor, beta guanine
PREDICTED: Caiiis nucleotide fβmillarts similar to binding protein guanine nucleotide (G protein), Binding protein (G p-'otein); afμt<3 inhibiting alpha inhibiting
Cfa.3177. activity polypeptide I XM 5354 activity LSI at 3.SSE-02 4.46E-OIi t.59 (LOC47S227); mRNA 99,6 02 GNA11 polypeptide 1 guanine nucleotide
CfaAfftc.31 binding prot
Homo sapiens G-protein ein 263.1. S 1 gamma- 13 subunit (G protein), s at «.97E-02i 4,48E-Oi 0,77|f"RNA; compiete cds SS, 6 AF 119663 GNG12 aamma 12 familians similar to guanine Guanine nucleotide' nucleotide binding protein binding prot qi}/G<s)/G(O) 9ammβ- ein
Cfa.10270 3 subunit (LOC4S3783); XM 5409 (G protein), .2.A1 at S.60E-O2; 4,SOE-OU 0.72 mRNA 99,6 04 GNG3 gamma 3 fsmillaris similar to ς'ucossmιπe-6- pfϊosprvβte deaminase 2; Piuco$amine-6-
Cfa.1846. tramcnpt variant 1 XM 8443 phosphate LSI at 8.S4E-02! 4,57E-OIi t.67 (LOC608049); mRNA 97 24 GNPDA2 deaminase 2
PREDICTED: Canls fllucosamine- familians simiiar to phosphat giucosamine-phosphase e N-
Cfe.1666. N-aciϊtyrtransferase 1 XM 5374 acetyltransferas 1.S1 at J..53E-O2; 4.46E-01 l.SS (LOC4S033S); niRNA 82.2 48 GNPNAT1 e 1 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000353_0001
352 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000354_0001
353 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000355_0001
354 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000356_0001
355 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000357_0001
356 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000358_0001
357 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000359_0001
358 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000360_0001
359 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000361_0001
360 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000362_0001
Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000363_0001
362 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000364_0001
363 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000365_0001
364 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000366_0001
365 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000367_0001
366 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000368_0001
367 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000369_0001
368 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000370_0001
369 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000371_0001
370 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
PREDiCTEO: Equus similar to eabaϋus similar to guanine guanine nucleotide nucleotide tending prctem-like 3 binding prot (nucleolar) ein-
Cfa.10532 (LOCI 000*0056); XM 0014 LOC 1000 like 3 .1.A1 at 5.63E-02 4.SOE-OIi £.43 mRNA 43.S 92431 60056 (nucleolar) cabailus similar to Sorting nexin-4
Cfa.2091, (IOC.00060493); XM 0019 LOC 1000 hypothetical 1.S1 at i.ise-02 4.46E-OIi £.59 mRNA 61.5 16714 60493 LOC100060493 similar to
PREDICTED: Eqυus SEC22 vesicie caoailus similar to trafficking SEC22 vesicle trafficking prot protein homolog A ein
Cfa.9428. (UX10006059S); XM 0015 LOC 1000 homoloQ A (S. 1.81 at 5.8SE-03 4.46E-01 1.3S mRNA 01930 60595 cerevisiae)
PREDICTED: eqυus cabailus similar to ozf
CfaAfix.85 (LOC10006O65S); partiai XM 0014 LOC1000 7.1.S1 at 1.99E-02 4.46E-OIi £.45 mRNA 96 94019 60655 similar to ozf
PHEDJCTEurEqυtjs obailu5 similar to PEST proteolytic signal similar to PEST containing nucteai proteolytic protein; transαlpt sional variant 1
Cfa.16541 (LOC100061942); XM 0015 LOC 1000 containing
.1.81 at 4.32E-02! 4.47E-01 Ui mRNA 93.4 03437 61942 nuclear protein
PREDICTED: Efluus
CfaAffeUO cabailus similar to CASl domain containing i similar to CAS1 (LOC100062437); XM 0014 LOC1000 domain
Figure imgf000372_0001
3.78E-O^i 4,46S-Ol! 1.39 mRNA 67.6
CfaAffit,44 catø;lus similar to si hCG2044798 milar to S8.1.S1 a (LOC100062670); XM 0014 LOC1000 KiAA 1956 t 6.32E-O^i 4,SOS-Ol! 1.31 mRNA 87 94163 62670 protein caballuts similai to heparan sulfate D-
CfaAffx,27 giueosaminyl 3-O- sulfotransferase 3Bl
403.1.51 (LDC100063069); XM 0019 LOC1000 hypothetical
2.21E-02I 4.46E-OlI 1.36 mRNA 70.3 18383 63069 LOC100063069
PREDICTED: Eqυυs cabailus similar to
CfaAffx.21 Rbroυs sh«atti CABVR hypoth binding protein etical
529.1.51 (LOC1000633S6); XM 0014 LOC 1000 protein
U1E-02! 4.46E-01 0.7S mRNA 43.6 LOC 100063356
PREDICTED: ERUUS catø;lus similar to Sister chromatid cohesion protein PDSS homotøg A (Sister chromatid coheston protein 112) (SCC-112) (CPiI proliferatlon-lnducirg gene 54 protem)
Cfia.9936. (LOC1000639S9); XM 0014 LOC 1000 similar to SCC- 1.A1 at 2.69E-02I 4.46£-0l! 1.33 mRNA 79.3 97764 63999 112 protein Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000373_0001
372 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000374_0001
373 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000375_0001
374 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000376_0001
375 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
hypoth
Homo sapiens cDNA etical
Cfa.9690, f U40058 Rs; done LOC2830 protein 1.A1 at 8.10E-02! 4.5SE-01 1.36 TCOl!«000i80 37.7 AK097377 ZS LOC263070
CfaAfjx.14 PR6O1CT6D: ftattus notvegicus hypothetical 32.1.51 a IOC36372S XR 00822 LOC3637 hypothetical I 1.47E-02I 4.46E-OIi 0.74 (LOC363725); mRNA
CfaAfSx.20 famifiaris hypotheticaf hypoth protein LOC4O3S31; etical
175.1.S1 transcript variant 3 XM 8513 LOC4035 protein at S.89E-02! 4.50E-01 0.7 (LOC403S31); mRNA 98.2 48 31 LOC403531
PREDICTED: Pen similar to T-ceii
CfaAffx,17 troglodytes similar to T- transcription cell transcription factor-
1S8.1.S1 4 long C-tcrminal XR 02333 LOC4507 factor-4 long C: s at S.39EO2! 4,62E-Oi 0,76 (I.OC4SO743); mRNβ, 94,7 43 terminal
PREDICTED: Pan si tuxjiodytes similar to milar to OTU αa.1161. OTU domain containing XR 02312 LOC4642 domain 1.S1 at s.sse-02 4.SOE-OIi ,47 68 (LOC464282); (rRNA 58,4 6 82 containing 6B
PREDICTED: Pan similar to tuxjiodytes similar to Phosphatidvtino Pi>osptiat!dylinosito] 4-
Cfa.46,1Λi kinase type 2 beta XR 02536 LOC4711 sttoi 4-kinaβe
1 at 4J0E-02! 4.47E-0.i 1.44 (LOC47U60); mRNA 76,2 60 type 2 beta famlliaiis similai to
Cfa.5209. CG9987-PA XM 5317 LOC4745 similar to
Ii 6.78E-02; 4,S2£-Ol! 1,36 (LOC474S34); mRNA 99,3 24 CG9987-PA
PKcDiCTcEircanis faniiliafis hypothetical
Cfa.12058 10CWS3S XM 5317 LOC4745 hypothetical ,1.A1 s a^ S.09E-02! 4.50E-01 ..34 (LOC47453S); mRNA 99.S 64 35 LOC474535 familisrws similar to similar to
CfaAffit,49 chromosome 2 open chro reading frame 30; mosome 2
S3.1.S1 S transcript variant I XM 5318 LOC4745 open reading at 2.62E-O^i 4,46S-Ol! 1.33 (LOC474S93); mRNA 99,8 22 93 frame 30 famlliaris similar to similar to chromosome 2 open chro reading frame 30; mosome 2
Cfa.3321. transcript variant 3 XM 8599 LOC4745 open readinp. 1.S1 at ^,46E-02l 4.47E-0U t.44 (LOC474S93); mRNA 100 68 93 frame 30 familiaris tUtv'ar to similar to
CfaAffx,26 PtOtdn CSortδ (GAP-like Prot r5 pωtdn N6t); transcript ein C5of 21.1.S1 a variant 2 (I.OC474690); XM 8458 LOC4746 {GAF-like t 9.94E-02; 4.65£-0ll 1.43 mRNA 100 94 90 protein N61 )
376 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000378_0001
377 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000379_0001
378 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000380_0001
379 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000381_0001
380 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000382_0001
Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000383_0001
382 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000384_0001
383 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
similar to Dynein intermediate
PREDICTED: Canfs fβmlliaris similar to chain 2, Dynem intermediate cvtosolic (DH iC chain 2; cytosolic (DH 1C 2) (Cytoplasmic 2) (Cytoplasmic dyreln intermediate chain 2); dvnein
Cfa.6063. transcript variant i XM 5359 LOC4787 intermediate
1.A1 s at 4.4SE-02! 4.47E-OIi Ul (LOC478797); mRNA 92.4 61 97 chain 2) similar to Dynein intermediate
PREDICTED: CartlS chain 2. familians simiiar to Dyπeiπ intermediate cvtosolic (DH iC chain 2; cytosolic (OH IC 2) (Cytoplasmic 2) (Cytoplasmic dyrein dvn intermediate chain 2); ein
Cfa-10613 transcript variant 3 XM 8546 LOC4787 intermediate
.1.A1 at 1.35E-O2 4.46E-OIi 1.37 (LOC473797); mftNA 9S 64 97 chain 2) familiaris similar to histone similar to
CfaAf6t,19 aminotransferase t histon (predicted); t/ansσ'pt e
978.1.S1 variant 3 (lOC47879θ); XM 8449 LOC4787 aminotransfera at 4.12E-Oi! 4,46S-Ol! 1.S9 mfWA 100 87 99 se 1 (predicted)
CfaAffr,47 PKEDICTEDT cSnIs familians similar to 1.1.S1 s tubulin; beta; 2 XM 5359 LOC4788 similar to at 6.63E-02 4.51E-01 1.37 (LOC47882S); mRNA 99 87 25 tubulin, beta, 2
PREDICTED: Capis similar to tiqger famitiaris slrrxlar to transposabi $9ger transpσsabfe e
CfaAffx.88 element cferived I XM 5359 LOC4788 element derived
8.1.S1 at i.OlE-02! 4.46E-OIi IA (UX47gs29); mRNA 97,7 91 29 1
PfiEDICTED: Canis similar to solute fβmlliaris similar to carrier family 39
CfeAfϊx.15 solute carrier farmiy 39 (zinc (tine trartsporter); 878.1.81 !»ernbet 10 XM 5360 LOC4788 transporter), s at 8.72EO2! 4,59E-OIi t,3 (I.OC47SSS0); mRNβ, too 12 50 member 10 fawiflsris sitriilsr to basic similar to basic
CfaAffx,18 ieudne zipper and \M2 l ctomains 1; transcript eucine 2tpper 492.1.S1 variant 5 (LOC476855); XM 8528 LOC4788 and W2 s at 4.31E-02! 4.47E-01 !.• 4 mRNA 91.3 68 65 domains 1 familians similar to basic similar to basic
CfaAf6t,18 ieucine .Ippei- and W2 domains 1; transcript leucine zipper
4B9.1.S1 variant 3 (IOC47SS&5), XM 8440 LOC4788 and W2 H 1.95E-O^i 4,46S-Ol! 1.4S mRNA 94.1 domains 1
PREDICTED: Canis familiaris slrrnlβr to CDC' si sltce kinase 1 lsoform 1; milar to CDC-
Cfa.9172. transcript variant 6 XM 8529 LOC4788 like kinase 1 1.S1 s at S.96E-02 4.53E-0U t.39 (l.OC47gδ€6); mRNA 97,S 96 66 isoform 1
384 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat An ii.
Figure imgf000386_0001
385 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
similar to
PREDICTED: CSflis membrane- familia.-is similar to associated
CfaAfftc.24 memδfane-associaKd guanylat guanyiate kinase-related e
6S9.1.S1 (MA6I-3) (LOC479761); XM 5368 LOC4797 kinase-related at 9.04E-02 4.60E-OIi 0.76 mRNA 100 89 61 (MAGI-3)
PREOiCTED: Cams similar to familiaπs simitar to receptor- receptor-ιnteracfcin§ int fβctof i isofofm i; eracting,
Cfa.765.1, transcript variant I XM 5370 LOC4799 factor 1 isoform S1 s at 3.01E-O2 4.4SE-01 £.44 (IOC479906); mRNA 99.7 Q6
PREDICTED: CsniS similar to
CfaAHx.30 fsmiltaris similar to ubiquitin- ubiqujtm-cortjusatirts
685.1.S1 enzyme E2N XM 5370 LOC4799 coniuqating at S.36E-02 4.50E-OIi 0.76 (I.OC479932); mRNA 97,5 58 32 enzyme E2N
CfaAffx.24 PKEDicTEDTcaras familia.-is hypothetical
224.1.S1 .OC4S0097 XM 5372 LOC4800 hypothetical fit 2.16E-O2; 4,46E-Ol! 0.75 (LOC4S0097); mRNA ioo 19 97 LOC480097
CfaAffx,27 PKEuϊCTEDϊXaπis familians similar to 165.1.S1 CG6931-PA XM 5372 LCX:4801 similar to S at s.szE-oai 4.SOE-Ol! ..37 (LDC4S01S6); mRNA too 79 56 CG6931-PA
OaAffx.21 wtuic I fcu: cants si familiaris similsr to milar to 879.1, S1 Proton CS4orfl04 XM 5374 LOC4803 Protein at ^,93E-02 4.48E-0U ..34 (LOC490313); mRNA 100 35 13 C14orf104
PREDICTED: Cams similar to familiars similai to dvnein. ύynain; cytoplasmic; cytoplas neavy polypeptide 1; mic.
Cfa.20805 transcript variant 8 XM 8634 LOC4804 heavy
,1,S1 s at S.74EO2! 4,50E-OIi 0,76 (IOC4SO437); mRNA 96 9 90 37 polypeptide 1 similar to lmportin alpha-
2 subunit
PREOiCTED: Cams familians similar to (Karvopherin l<nportm alpha-2 subunit alpha-2 (Karyopherin alpha-2 subunit) (SRFi-
CfeAfϊx.18 subunit) {SRPl-alpM) aloha) (RAG (RAG cohort proteir 1); 054,1.81 transcript valiant 3 XM 8569 LOC4804 cohort protein s at 3.00EO2! 4,46E-OIi t,34 (I.OC4SO469); mRNA 99,5 28 69 1)
PREDICTED: Canis similar to
CfeAffx.19 familiaris similar to testicular call adhesion testicular ceil 647.1, S1 moiecute i XM 5375 LOC4804 adhesion
9.47E-O3 4.46E-OIi 0.76 (LOC48O476); mRNA 100
PREDICTED; Csnis si faniillafis similar to milar to
Cfa.374.1, ankyrin repeat domain XM 5378 LOC4807 ankyrin repeat
A1 at 1.99E-O2! 4.46E-OIi 1.42 26 (LOC480753); mRNA 48 73 53 domain 26 similar to
PREDICTED; CsnlS Gamma-taxiiin faniillafis similar to (ϋpopolvsacch
CfaAfTx.19 Gamms-tBxilin arid (Lipopoiysaccharide e specific
577.1.51 specific response protein XM 5379 IOC4808 response s at 7.48E-03 4,46£-0li i.84 S) (IOC4SO8S3); mWA 41.9 70 53 protein 5)
386 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000388_0001
387 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000389_0001
388 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000390_0001
389 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000391_0001
390 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000392_0001
Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000393_0001
392 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000394_0001
393 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000395_0001
394 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000396_0001
395 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000397_0001
3% Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000398_0001
397 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000399_0001
398 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
PREDICTED: Macaw hypoth mulatta hypothetical etical
Cfa,553t, pfOtein LOC69S648 XM 0010 IOC6956 protein 1.A1 at 3.36E-02; i.-wε-oi! 1,16 (LOC69S618); mRNA 68.1 84170 48 LOC69S648
PREDICTED: Mϋcaca similar to nwljtJ. similar to mitochondrial mitochondrial ribosomal
Cfa.24Q6, protein SlO XM 0010 LOC6958 liposomal 1.A1 at i.l8EO2! 4,46E-Oi t,6 (LOC69SB92); mRNA 35 5 87232 92 protein S10 mulstta similar to bipartite mobf- si containing 2; transcript milar to
Cfa.16361 variant 1 (LOC696517!; XM 0010 LOC6965 tripartite motif- .1.S1 at S.90E-02! 4.65E-O1 1.S6 mRNA 49.4 86174 17 containing 2 similar to
PREDICTED: Mscaca vitamin K mulatta similar to epoxide vitamin K epoxide r reductase complex; eductase
Cfa.13301 subunΛ Hike 1 XM 0010 LOC6975 complex. ■1A1 at 2.SSE-O2! 4.46E-OIi 1.34 (LOC$9?59i); mRNA 31.3 88069 91 subunit 1-iike 1 similar to low
PREDICTED: Macsca density muiatta simitet to icvv lipoprot density lipoprotein ein
Cfa.8912. feceptβf-raiated protein XR 01033 LOC6976 receptor- related 1.A1 at 5.26E-CK); IMZ-Qi, 1,75 11 (LOC6976S3); mRNA 34,4 52 protein 11
similar to CTD small phosphatase- like protein (CTDSP-like)
(Small C- terminal domain phosphatase 3)
(Small CTD
PRH3ΪCTED: Macao phosphatase 3) mutettfl similar to CTO (SCP3) smart phospr«it3sa-like protein (CTDSNike) (Nuclear LIM (Smsli C-tβf miral interactor- domain phosphatase 3) interactinq (Smali CTO phosphatase 3) (SCP3) (Nutl«ar UM factor D (NLI- intefβctor-interActiiig interacting factor i) (NU- factor D (NIF- ■ntefacting factor 1) lik (NIHike protein) e protein) αa.5789. (RSSP3) (YA22 ptotein) XM 0010 LOC6978 (RBSP3) (YA22 1.A1 at S.69E-02 4,50E-OIi I.4S {.„ (LOOS97S9S); fnftNA 69.4 86442 protein) (,.,
PREDICTED: Mscaca si mulatta similar to milar to
Cfa.9673, Pioteto C6orf203 XM 0010 LOC6981 Protein 1.A1 s at 6.48EO3! 4,46E-Oi t,S9 (I.OC69S10S); mRNA 86,9 90337 08 C6oιf203
399 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000401_0001
4(X) Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000402_0001
Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000403_0001
402 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000404_0001
403 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000405_0001
404 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000406_0001
405 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000407_0001
406 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat An ii.
Figure imgf000408_0001
407 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000409_0001
408 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000410_0001
409 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000411_0001
4J0 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000412_0001
4J l Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000413_0001
4J2 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000414_0001
4J3 Tabte 8:Genes DiffereπSiaify Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000415_0001
4J4 Tabte 8:Genes Differeπiiaϋy Expressed in lymphocytes from Fat Animals fed an either a high protein diet or She same diet with added fish oii.
Figure imgf000416_0001
Table 8 Genes Differertliaϋy Expressed in lymphocytes from Fat An il
Figure imgf000417_0001
4H> Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000418_0001
4J7 Table 8 Genes Differ ertfcaϋy Expressed in lymphocytes from Fat An il
Figure imgf000419_0001
4J8 Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000420_0001
4)9 Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000421_0001
Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000422_0001
42 ϊ Table 8 Genes Diffeterttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000423_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000424_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000425_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000426_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000427_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000428_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000429_0001
Table 8 Genes Di?fererttia!ly Expressed in lymphocytes from Fat An il
Figure imgf000430_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000431_0001
Table 8 Genes Differertliaϋy Expressed in lymphocytes from Fat An il
Figure imgf000432_0001
43 ϊ Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000433_0001
Table 8 Genes Differ ertfcaϋy Expressed in lymphocytes from Fat An il
Figure imgf000434_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000435_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000436_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000437_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000438_0001
Table 8 Genes Differ ertfcaϋy Expressed in lymphocytes from Fat An il
Figure imgf000439_0001
Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000440_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000442_0001
44 ϊ Table 8 Genes Differ ertfcaϋy Expressed in lymphocytes from Fat An il
Figure imgf000443_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000444_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000445_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000446_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000447_0001
Table 8 Genes Differ erttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000448_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000449_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000450_0001
Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000451_0001
4SO Table 8 Genes Di?fererttia!ly Expressed in lymphocytes from Fat An il
Figure imgf000452_0001
4SΪ Table 8 Genes Differ ercfcaϋy Expressed in lymphocytes from Fat An il
Figure imgf000453_0001
4S2 Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000454_0001
4S3 Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000455_0001
4S4 Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000456_0001
4S5 Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000457_0001
4S6 Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000458_0001
4S7 Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000459_0001
4S8 Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000460_0001
4S9 Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000461_0001
Table 8 Genes Di?fererttia!ly Expressed in lymphocytes from Fat An il
Figure imgf000462_0001
46! Table 8 Genes Differ erttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000463_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000464_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000465_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
faimiiiarte similar to thfeoFiyi-tRNA
Cfa.2825. synthetase XM 5365 threonvi-tRNA
1.A1 at 3.59E-Q3 4,SSE-Oi 1.33 (LOC47937Q); mRNA 76.6 09 TARS synthetase fømltiaπs sitnϋar to
CfaAffx.93 Threonine aspartase I taspase. (Taspase i); trarsseipt
49.1.S1 a vacant <» {UXtt7735i>; XM 8532 threonine t 2.64E-O2 4,4SE-Ol LS triRNA too 64 TASP1 aspartase. 1 fawiβsffe simtsar to ϊax± Taxi (human T- (human T«ceif leukemia ceii ieukemia virus type I) binding virus typ protein i; transcript e i)
Cfa 10871 variant S (LQC47S2W; XM 859? binding, protein.
.1.At s at 9.77EMK 4,64E-Ol 1 34 mRNA 99.5 31 TAX18P1 1 familiaris sifπiiar to Taxi Taxi (human T- (human 7-ee!i teutema ceil leukemia
CfaAffx.54 virus type 1) binding virus typ protein i; traπsoipt e i)
37.1. S1 S variant S (LOC475264); XM 8597 binding protein at 3,91E-02 4.S9E-01 IA mRNA ioo 87 TAX1BP1 1
CfaAffx.16 PREDICTED; Cams TBC 1 do farniiiafis similar to TBCl main
57.1. S1 a domain family; member XM 5316 famiiv, member t 6.72E-Q2 4.SiE-Oi: i.S? IS {LOC4744S1); mRNA ioo 81 TBC1 D15 15
CfaAffx,97 PREDICTED; Cams TBC 1 do famiiisn-; similar to TBCl main
40.1.S1 s domain family mernbet XM 5427 famiiy, member at 8.43E-Q2 4.S7E-01! i.32 S (LOC4SS6S1); mRNA 99.ll 71 TBC1 D5 5
PREDICTED- Equus TBC1 domain csb≤itus TBCi domaiii f fawiSy; rnember 9 (with amiiy, member
Cfa.3145. GRAM domain) XM 0015 9 (with GRAM
1.A1 at 4 66E-02 4.48E-Oi: 1.56 (TSCtOS); mRNA 54.7 01060 TBC1 D9 domain)
CfaAffx.14 famiiiaris smiiar to TAMK-binding kinase 1,
84.1.S1 a transcript variarst 2 XM 8557 TANK-bindinQ t 2.63E-O2 4.45E-01 1.3S {LOC4ail45}; mrøA ioo 42 TBK1 kinase 1
CfaAffx.25 PHtDiC f to: Cants fsmϋiaiis SitniSar to 534.1. S 1 P?aSAPiP2 protein XM 5481 TBKI binding s at 6.17E-02 4,SOE-Ol 0.76 (LOC491043), mftM ss s 63 TBKBP1 protein 1
PREDICTED: Cants transcription faniifSari≤ sstniiar to transcription elongation elongation
Cfa.9500. factor A {SH}-!lke 1 XM 5381 factor A (Si 1.S1 at 2 13E-O2 4.46E-01! 132 (LOC481000); mRNA 95.9 21 TCEAL 1 iike i
PREDϊCTEO: Cants faroiisaris sitπfiar to TransCTiptiOfs rfoπgafion reguiator 1 (TATA fcox- bifidtrtg protein- assoαst«d factor 2S) (Trafiscription factor CAISO) (pi44) (Forrπin- tr binding protein 28} (RSP anscription
Cfa 21472 2S}; tfartBCiipt variant S XM 8538 elonga.tjon.
.1.S1 s at 5.9ΪE-O2 4,SOE-Ol 1.3? (LOC47B052); mRNΛ 70.9 36 TCERG 1 regulator .1 Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000467_0001
Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000468_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000469_0001
Table 8:Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000470_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000471_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000472_0001
47Ϊ Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000473_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000474_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000475_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000476_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000477_0001
Table 8 Genes Differerttiaϋy Expressed in lymphocytes from Fat An il
Figure imgf000478_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000479_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000480_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000481_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000482_0001
48 ϊ Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000483_0001
Table 8 Genes Differ ertfcaϋy Expressed in lymphocytes from Fat An il
Figure imgf000484_0001
Table 8 Genes Differentially Expressed in lymphocytes from Fat An il
Figure imgf000485_0001
Diets Coinamins Hiiiher Amounts Of Lonα Chain FaUv Acids Promote Wekht Loss And Can Be Used To Re-Program The Gene Expression Of The Animal So That It Reflects A
Propensity To Become Lean And Potentially Maintain Leanness
}Θ0261| The data obtained from w vtim ingredient screens discussed above indicate that some ingredients that are high in long chain fatty acids ( see Table 5} may have the potential to affect the expression of genes involved in tat metabolism in a w ay thai would promote leanness of the animal as a whole. This ss determined by analyzing data obtained from adipose tissue and from the ingredient assays discussed above using conventional computer algorithm analyses Code for algorithms useful in this regard are familiar to one of skill in the art and may be developed v* ithouf undue experimentation. An example of such code is provided below:
100262] SELECT A.PROBE, TO CHAR* AVG< DECODE* A.EXPTDAY. W GENEJS[QRMJNT. null)) AVG(DECODES A.EXPTDAY, 1D 14',
GENEJ^QRMJNT. nuinvwww. WW } FATLEAN _FC\
STATS JF JTESTJNDEPUC A.EXPTDAY. GENE-NORM JNT) REVALUE.
BTOP-HTT-DEF.
J00263] COUNT(DISTI NCT CiNGRHDlENT), COUNTIDf STiNCT
D.ΪNGREDΪENT)
100264] FROM GERIATRICS ..RNRM2 A. TOP. PROBE . ANNOT..2..3 B,
FΪLTJNDΪVJCΕLLSJ- C, F1LT _ACROSS _4_CELLS_2 D WHERE
A. PROBE=B. PROBE ΛND A.PROBE=C. PROBE (+) AND A PROBE=D PROBE
{÷) AND UPPER(A.PROBE) NOT LIKE lAFFX%" GROUP BY A.PROBE,
B.TOPJ]TTJ)EF HAVING STATS-T-TESTJN DEPLK A.EXPTDAY,
GENE . NORMJNT) <= ,01 AND A VGf DECODEt A, EXPTDA Y, 1DO',
GEN E NORM JNT. null))/A VG(DECODE(A.EXPTDAY, 'D ! 4'.
GENEJSfORMJNT. null}} >=== 5 AND SI)M(DECODE(PAMCALL, 1P1. i . 0» ===
40 ORDER BY PROBE
[0Θ265J To confirm ihe findings s«mmari/ed in table 5 above thai some biøaetive dieiar> componems such as EPA DHA ( 1.5: 1) as found in fish oύ are more effective in bringing weight loss in dogs compared Io other hioactive dietary components by acting on key genes associated with fatty acid metabolism (as show n in fable >) tSnee high ptotem diets containing eithei no added long chasπ faH) acids {Diet A) or added hnolcmc acid (approximate!} 1 % based on K)O0O
Figure imgf000487_0001
matter baas. Diet B) or EP
Figure imgf000487_0002
0 30° 9 « 20 °<Λ (Diet t ) were dev eloped fox compauson to a high fibei diet thai is known to induce weight loss in dogs In the sl«d> , 45 cluucailv
Figure imgf000487_0003
e all fa st fed a MUπfiøiial!) complete control diet for M) da> s pπoi to the start of the test Λftei the mmal 30 da>s, the dogs aie landomi/ed into 4 gioups Tliiee of the four groups receiv e one of the test diet^ and one gtoup is given the high flb«i diet as a coauol for a set period of time e tj , 4 months Results indicate that the thtee expcrmienyl foods (Diets \ B and ( ') hax c substantialK higher dmcsubslitv than the higher fjbej iood Results a!su mJtcate that
Figure imgf000487_0004
3H0^ of ihe dogs consuπimg the food containing EPΛ DHA ieach then w eight loss goal at 90 davs Inteiesuπgh dogs coiiNumtng the ϊrPA DH \ food also maintain lean muscle mass and bone muieial content Tbe
Figure imgf000487_0005
ei diets containing FPA/DΪI A. ma\ be as effectn e as high Tibet dset^ in affecting weight lo^s
4$b
Figure imgf000488_0001
Possible W eight Lυss Maintenance fcκpeumeni
J0Θ266J Btwed on ihc results of the weight loss experiment discussed above ύ is h\ poihesi/ed thai animals fed a diet containing EPA DH Λ will πo£ onh lose w eight but also will maintain the loss foi a longer peuod of time cumpaied to animate fed the otSici test and contiol high fϊbet diets
[00267] In ordet to chaπictcu/c the effects ol Diets Λ B, and C and the hiv>h fϊgher diet on w eight loss maintenance, one could peifotm, for example, the loilowing type of evpeiiment
|OΘ2feS| Ov erweight animals ma\ be fed the iout diffeiein diets (as. descπbed m FxarapJe 4) until thev teach an optimum lev el of icurtrteW Thev nuv then be landorai/ed aαd dn ided into subgtoups that eithei continue to be fed the same test diet that thev vveie led
Figure imgf000488_0002
diet that is niuntioπall) balanced but is not designed to induce or maintain weight loss and does not include appicαabie amounts of Imolenic aesd or M3A DH 4 foi example [00269| 1 he animal
Figure imgf000488_0003
then be obsen ed foi a set peuod of time e g , up to 3 months v nil their weights iecoided daiU then bod> eonduion scores determined week H and thcu pcicentage tod} fat determined on a rnomhiv basis using conv entional DEX \ (echnoios-ies
Example 6
MctabolomJc Profile of Lean and Ox ci weight Dogs
{Oθθl j Fifty-two neutered spayed beagles (a\eτage age 8.6 i 3 1 years) were identified for this study Dogs were weighed, given a body condition score (BCS: 1 lean, 3 ideal and 5 obese) and a plasma sample was collected. Of the fifty-two dogs identified, 24
Figure imgf000489_0001
= 1 1.2 ~ 1» kg) and 38 as ovei weight obese { BCS ^ 9 0.7. BW 14 4 i 3.6 kg) Meiabolomic profiling of plasma samples was pei formed by Metabolon i Durham. NC) f~ϊest analysis was applied to log-transformed. da> normalized data. Metabolites having a P -- C) 05 {following a false discovery rate adjustment value of 0.1 } were considered different among the tv>o groups. KEGG and HMDB identifiers were from commercial databases. Analysis of the plasma found differences in 20 metabolites between the two groups. Of the metabolites identified. 15 had nicrcased fold-changes and 5 had decreased fold-changes in the overweight group when cυrnpaied to the lean gtυup The metabolites with increased fold changes in overweight dogs were giutarnine, 3-methylhistidine, lysine, isolencine, valine, citruSline, oxidized glutathione, glutatnyKaiiπc, pyroglutann h aline, gamma- glutamy Heucine, jiarania-giuiamylniethjonine, μamma-glutamv Iglutamine, stearoylglyceroi (moiiostearin). 3-hydroxybiitγrate and citrate Tfie metabolites with deαea.sed fold changes m
Figure imgf000489_0002
dogs %ere p-cresol sulfate, 1 5-aπh>drog1ucitoL glycerate, docosahcxaenoatc and tlireonate There were minimal differences in metabolites for gendei as all dogs weie spayed or neutered. In summary, amino acid metabolism, lipid metabolism, carbohydrate metabolism mid oxidative stress were different between ovei weight and lean dogs
J0Θ02J All of the references cited herein and appended hereto, including patents, patent applications, literature publications, and the like, are hereby incorporated in their entireties by reference

Claims

yWhat is claimed is:
1. A canine compositions comprising;
(a) 26 wt. % to 35 wt % of crude protein on a dry matter basis;
(b) 7.5 wt. % to 8.5 wt, % of crude fat on a dry matter basis:
(C) 20 wt % to 30 vvt. % of total dietary fiber on a dry master basis: and (d) 10 wt. % to 20 wt. % of crude fiber on a dry matter basis.
2. The composition of claim K wherein the protein is present in 28 wt. % to 33 wt. %.
3. The composition of claim 1. wherein the protein is present in 30 wt. % to 31 wt, %.
4. The composition of claim S , wherein the crude fat is present in 7.6 wt. %. 8.0
Wt. %
5. The composition of claim ! , wherein the total dietary fiber is present in 22 wt, % to 28 wt. %.
6. The composition of claim 1, wherein the total dietary fiber is present m 24 wt % to 26 %.
7. The composition of claim 1 , wherein the crude fiber is presem in 12 wt. % to 18 wt. %.
8. The composition of claim 1, wherein the crude fiber is present in 14 wt. % to 16 %.
9. A feline compositions comprising:
(a) 30 wt, % to 37 wt. % of crude protein on a dry matter basts;
(b) 7.5 Wt, % to 9 wt. % of crude fat on a dry matter basis:
(c) 30 wt. % to 35 wt. % of total dietary fiber on a dry matter basis: and
(d) 20 wt, % to 25 vvt. % of crude fiber on a dry matter basis. A o ney D e . 8684 JS HL
10. "The composition of claim $, wherein the protein is present in an amount of 31 vvt. % to 36 wt. %.
H. The composition of claim 9, wherein the protein is present in an amount of 33% to 35%.
12. The composition of claim cλ wherein the crude fat is present in an amount of or 8.0 wt. %, 8,5 svt. %
U. The composition of claim S , wherein the tøtai dietary fiber is present in an amount of 3 i wt. % to 34 wi. %.
I i. The composition of claim K wherein th« crude fiber is present in an amount of 21 wt. % to 24 wl. %.
!5. A method of treating a disease or disorder comprising administering a composition of claim 1 to a canine in need thereof.
Ib. The method of claim 1 5 wherien the disease or disorder is obeiity.
!7. A method of treating a disease or disorder comprising administering a composition of claim 9 to a feline animal in ns&ά thereof,
18. The method of ciaim ! 5 wherein the disease or disorder is obeskv.
PCT/US2010/020249 2009-01-06 2010-01-06 Compositions and methods for treating disorders associated with overweight animals WO2010080826A1 (en)

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CN110022853A (en) * 2016-12-28 2019-07-16 三得利控股株式会社 Composition is used in the different aspartic acid transmethylase activation of Protein L-

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WO2002056702A1 (en) * 2001-01-17 2002-07-25 Royal Canin Sa Dry feedstuff for controlling excess weight and obesity of dogs
WO2003061706A1 (en) * 2002-01-22 2003-07-31 Mars, Incorporated A weight management system for obese animals
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Publication number Priority date Publication date Assignee Title
CN110022853A (en) * 2016-12-28 2019-07-16 三得利控股株式会社 Composition is used in the different aspartic acid transmethylase activation of Protein L-
CN110022853B (en) * 2016-12-28 2022-05-03 三得利控股株式会社 Composition for activating protein L-isoaspartic acid methyltransferase

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