WO2001092278A2 - Haplotypes du gene rlbp1 - Google Patents

Haplotypes du gene rlbp1 Download PDF

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Publication number
WO2001092278A2
WO2001092278A2 PCT/US2001/017252 US0117252W WO0192278A2 WO 2001092278 A2 WO2001092278 A2 WO 2001092278A2 US 0117252 W US0117252 W US 0117252W WO 0192278 A2 WO0192278 A2 WO 0192278A2
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WO
WIPO (PCT)
Prior art keywords
rlbpl
haplotype
seq
gene
nucleotide
Prior art date
Application number
PCT/US2001/017252
Other languages
English (en)
Other versions
WO2001092278A3 (fr
Inventor
Julie Y. Choi
Amir Kazemi
Beena Koshy
Original Assignee
Genaissance Pharmaceuticals, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Genaissance Pharmaceuticals, Inc. filed Critical Genaissance Pharmaceuticals, Inc.
Priority to AU2001274995A priority Critical patent/AU2001274995A1/en
Publication of WO2001092278A2 publication Critical patent/WO2001092278A2/fr
Publication of WO2001092278A3 publication Critical patent/WO2001092278A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/172—Haplotypes

Definitions

  • the invention provides an isolated polynucleotide comprising a nucleotide sequence which is a polymo ⁇ hic variant of a reference sequence for the RLBPl gene or a fragment thereof.
  • the reference sequence comprises SEQ ID NO: 1 and the polymo ⁇ hic variant comprises at least one polymo ⁇ hism selected from the group consisting of adenine at PSl, thymine at PS2, adenine at PS3, adenine at PS4, guanine at PS5, adenine at PS6, cytosine at PS7, thymine at PS8, adenine , at PS9, adenine at PS 10, cytosine at PSll, thymine at PS 12, adenine at PS 13, adenine at PS14, thymine at PS 15, cytosine at PS 16, guanine at PS 17, thymine at PS 18, guanine at PS 19, adenine at PS20, adenine at PS21, cytosine at PS22
  • the invention provides a recombinant expression vector comprising one of the polymo ⁇ hic genomic variants operably linked to expression regulatory elements as well as a recombinant host cell transformed or transfected with the expression vector.
  • the recombinant vector and host cell may be used to express RLBPl for protein structure analysis and drag binding studies.
  • the invention provides a polypeptide comprising a polymo ⁇ hic variant of a reference amino acid sequence for the RLBPl protein.
  • Haplotype data Information concerning one or more of the following for a specific gene: a listing of the haplotype pairs in each individual in a population; a listing of the different haplotypes in a population; frequency of each haplotype in that or other populations, and any known associations between one or more haplotypes and a trait.
  • Polymorphic site (PS) - A position within a locus at which at least two alternative sequences are found in a population, the most frequent of which has a frequency of no more than 99%.
  • CTCTTCCYTCTCCCT (SEQ ID NO 11 and its complement
  • the nucleic acid may be isolated using any method capable of separating the two copies of the RLBPl gene or fragment such as one of the methods described above for preparing RLBPl isogenes, with targeted in vivo cloning being the preferred approach.
  • any individual clone will only provide haplotype information on one of the two RLBPl gene copies present in an individual. If haplotype information is desired for the individual's other copy, additional RLBPl clones will need to be examined. Typically, at least five clones should be examined to have more than a 90% probability of haplotyping both copies of the RLBP 1 gene in an individual.
  • the nucleotide at each of PS1-PS24 is identified.
  • the individual is preferably haplotyped using a direct molecular haplotyping method such as, for example, CLASPER System TM technology (U.S. Patent No. 5,866,404), SMD, or allele-specific long-range PCR (Michalotos-Beloin et al., supra).
  • CLASPER System TM technology U.S. Patent No. 5,866,404
  • SMD SMD
  • allele-specific long-range PCR Moichalotos-Beloin et al., supra.
  • Frequency data for one or both of the reference and trait populations may be obtained by genotyping or haplotyping each individual in the populations using one of the methods described above.
  • the haplotypes for the trait population may be determined directly or, alternatively, by the predictive genotype to haplotype approach described above.
  • the frequency data for the reference and or trait populations is obtained by accessing previously determined frequency data, which may be in written or electronic form.
  • the frequency data may be present in a database that is accessible by a computer. Once the frequency data is obtained, the frequencies of the genotype(s), haplotype(s), or haplotype pah(s) of interest in the reference and trait populations are compared.
  • the frequencies of all genotypes, haplotypes, and/or haplotype pahs observed in the populations are compared. If a particular RLBPl genotype, haplotype, or haplotype pah is more frequent in the trait population than in the reference population at a statistically significant amount, then the trait is predicted to be associated with that RLBPl genotype, haplotype or haplotype pah.
  • the RLBPl genotype, haplotype, or haplotype pah being compared in the trait and reference populations is selected from the full-genotypes and full-haplotypes shown in Tables 4 and 5, or from sub-genotypes and sub-haplotypes derived from these genotypes and haplotypes.
  • ANOVA is used to test hypotheses about whether a response variable is caused by or correlated with one or more traits or variables that can be measured (Fisher and vanBelle, supra, Ch. 10).
  • a mathematical model may be readily constructed by the skilled artisan that predicts clinical response as a function of RLBPl genotype or haplotype content.
  • the model is validated in one or more follow-up clinical trials designed to test the model.
  • a polymo ⁇ hic variant of a RLBPl gene fragment comprises at least one novel polymo ⁇ hism identified herein and has a length of at least 10 nucleotides and may range up to the full length of the gene.
  • such fragments are between 100 and 3000 nucleotides in length, and more preferably between 200 and 2000 nucleotides in length, and most preferably between 500 and 1000 nucleotides in length.
  • a RLBPl variant protein or peptide of the invention may be prepared by chemical synthesis or by expressing one of the variant RLBPl genomic and cDNA sequences as described above.
  • an antibody specifically immunoreactive with one of the novel protein isoforms described herein is administered to an individual to neutralize activity of the RLBPl isoform expressed by that individual.
  • the antibody may be formulated as a pharmaceutical composition which includes a pharmaceutically acceptable carrier.
  • any or all analytical and mathematical operations involved in practicing the methods of the present invention may be implemented by a computer.
  • the computer may execute a program that generates views (or screens) displayed on a display device and with which the user can interact to view and analyze large amounts of information relating to the RLBPl gene and its genomic variation, including chromosome location, gene stracture, and gene family, gene expression data, polymo ⁇ hism data, genetic sequence data, and clinical data population data (e.g., data on ethnogeographic origin, clinical responses, genotypes, and haplotypes for one or more populations).

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne des nouvelles variantes du gène de la protéine 1 de liaison du rétinaldéhyde (RLBP1). L'invention concerne plusieurs génotypes, haplotypes, ainsi que des paires d'haplotype existant dans la population générale des Etats-Unis pour le gène RLBP1. L'invention concerne également des compositions et des procédés d'haplotypage et/ou génotypage du gène RLBP1 chez un individu, ainsi que des polynucléotides définis par la séquence des haplotypes susmentionnés.
PCT/US2001/017252 2000-05-26 2001-05-29 Haplotypes du gene rlbp1 WO2001092278A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001274995A AU2001274995A1 (en) 2000-05-26 2001-05-29 Haplotypes of the rlbp1 gene

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US20761800P 2000-05-26 2000-05-26
US60/207,618 2000-05-26

Publications (2)

Publication Number Publication Date
WO2001092278A2 true WO2001092278A2 (fr) 2001-12-06
WO2001092278A3 WO2001092278A3 (fr) 2002-04-04

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/017252 WO2001092278A2 (fr) 2000-05-26 2001-05-29 Haplotypes du gene rlbp1

Country Status (2)

Country Link
AU (1) AU2001274995A1 (fr)
WO (1) WO2001092278A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022243386A3 (fr) * 2021-05-19 2022-12-29 Universität Bern Protéines mutantes de cralbp sensibles à l'oxydo-réduction

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
COTRAN ET AL.: 'Analysis of the DNA of patients with retinitis pigmentosa with a cellular retinaldehyde binding protein cDNA' EXP. EYE RES. vol. 51, 1990, pages 15 - 19, XP002906063 *
INTRES ET AL.: 'Molecular cloning and structural analysis of the human gene encoding cellular retinaldehyde-binding protein' J. OF BIOL. CHEM. vol. 269, no. 41, October 1994, pages 25411 - 25418, XP002906064 *
MAW ET AL.: 'Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa' NATURE GENETICS vol. 17, October 1997, pages 198 - 200, XP002906062 *
MORIMURA ET AL.: 'Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens' IOVS vol. 40, no. 5, April 1999, pages 1000 - 1004, XP002906061 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022243386A3 (fr) * 2021-05-19 2022-12-29 Universität Bern Protéines mutantes de cralbp sensibles à l'oxydo-réduction

Also Published As

Publication number Publication date
WO2001092278A3 (fr) 2002-04-04
AU2001274995A1 (en) 2001-12-11

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