CN1548553A - Reagent kit and primer for predicting susceptibility of type-II diabetes - Google Patents
Reagent kit and primer for predicting susceptibility of type-II diabetes Download PDFInfo
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Abstract
The present invention relates to reagent kit and primer for predicting susceptibility of type-II diabetes, and is especially reagent kit and primer designed based on one mononucleotide polymorphism site of newly distinguished type-II diabetes susceptibility gene SAC and used for predicting susceptibility of type-II diabetes. The present invention also relates to the application of SAC gene in preparing diagnosis preparation for predicting susceptibility of type-II diabetes.
Description
Technical field
The present invention relates to be used to predict the test kit and the primer of diabetes B susceptibility, more specifically, the present invention relates to utilize the test kit and the primer of prediction diabetes B susceptibility of a single nucleotide polymorphism (SNP) site design of the diabetes B tumor susceptibility gene SAC (SolubleAdenylyl Cyclase) of new discriminating.The invention still further relates to the application of SAC gene in the diagnostic reagent of preparation prediction diabetes B susceptibility.
Background technology
The massive epidemiology data shows that diabetes are a kind of disease of multifactorial inheritance with complexity of obvious genetic predisposition.Inherited genetic factors can obviously influence the susceptibility of body to Regular Insulin.Recent years, most researchers is devoted to seek the diabetes genes involved by the positional cloning method, promptly seeks interregional chain of the chromosomal DNA shared between ill family member.Found some the relative more rare single-gene forms in the diabetes B, (maturity-onset diabetes of the young MODY), is because sudden change has caused the β cell function low to be called young late hair style diabetes.These patients fall ill to the adult is early stage in pubescence usually, show as the glucose reactivity insulin hyposecretion.6 glucokinases of encoding respectively, transcription factor HNF1 α, 1 β, 4 α and insulin promoter factor (IPF1) are arranged, neurocyte differential protein (NeuroD1) in these Disease-causing genes.These transgenations finally cause the hyperglycemia mass formed by blood stasis.The sickness rate of these single-gene diabetes is also imprecise, estimates to account for 5% of all diabetes Bs.But, utilize the strategy of positional cloning to determine that the successful report of disease of multifactorial inheritance is also few merely.
Except the positional cloning method, the genes involved research to disease of multifactorial inheritance also has the most frequently used method of a kind of method at present, i.e. candidate gene method, the i.e. variation of direct study of disease candidate gene and the relation between the disease phenotype.This method is mainly based on the case-contrast association analysis to family or crowd.Association analysis does not need big family research but relatively certain or a certain cover are marked at the distributed degrees of patient and normal individual.If it is fairly obvious that certain mark distributes, so just can think that this mark is associated with disease phenotype in diseased individuals.But, because the Disease-causing gene position is not enough understood,, be primarily aimed at some metabolic pathways relevant and study in the candidate gene method with disease development selecting there is bigger blindness on the candidate gene.The positional candidate cloning method that above-mentioned two kinds of methods are combined has remedied the limitation of any single a kind of method to a certain extent, is the general strategy of employing of institute in the disease of multifactorial inheritance research at present.
Corresponding with the inherited disease research strategy, its research tool-polymorphism mark is also from restriction fragment length polymorphism (the Restrictive Fragment Length Polymorphism of the first-generation, RFLP), the microsatellite marker of the s-generation (Microsatellite Marker) develop into the third generation single nucleotide polymorphism (Single Nucleotide Polymorphism, SNP).Especially disease of multifactorial inheritance is being carried out need utilize a large amount of highdensity markers in case-contrast association analysis, preceding two generation polymorphism mark can not satisfy this requirement.Therefore, in recent years, SNP more and more causes people's extensive concern as third generation construction of genetic atlas person.
Single nucleotide polymorphism (SNP) mainly is meant on the genomic level by the caused dna sequence polymorphism of the variation of mononucleotide.It is modal a kind of in human heritable variation, accounts for more than 90% of all known polymorphisms.SNP extensively distributes in human genome, just has 1 in average every 500-1000 base, and its Estimate of Total Number can reach 3,000,000 even more.In recent years, along with the progress of human genome and genetics research, SNP also more and more demonstrates its significance in depth understanding between individuality and colony genomic variation or aspects such as polymorphism and disease research comprehensively.It is exactly its widely distributed property that SNP is used for the localized biggest advantage of diseases predisposing gene.Next is that it has the stability higher than little satellite, can reduce to greatest extent in the genetic process because the information loss that sequence variations caused.In addition, SNP is easy to realize high-throughout somatotype, can produce a large amount of results in the short period of time, and this point is that little satellite is incomparable.The These characteristics of SNP has determined it to be very suitable for multigenic disease, the especially Position Research of the disease that a plurality of minor gene caused resemble diabetes.Selecting appropriate cases and normal control, take the research method of association analysis, for SNP, is fit closely.
The inventor was engaged in Han People of North China diabetes B (non insulin dependent diabetes, NIDDM) assignment of genes gene mapping research in recent years always.In the full genome scanning work of formerly carrying out, the inventor has identified a plurality of tumor susceptibility genes site respectively, and they lay respectively at No. 1, and No. 12, on No. 18 and No. 20 karyomit(e).Wherein on No. 1 karyomit(e), have 5 zones that have tumor susceptibility gene.On this basis, the inventor attempts selecting suitable candidate gene from locating area, utilize SNP to carry out case-contrast association analysis, finally identified a diabetes tumor susceptibility gene (being the SAC gene) finally, and a SNP site relevant especially with the Han nationality in China diabetes B on this gene.Finished the present invention through further investigation thus.
Summary of the invention
According to an aspect of the present invention, a kind of test kit of predicting the diabetes B susceptibility is provided, and described test kit comprises based on the special primer that is used for pcr amplification of the sequences Design of Figure 1B or Figure 1A and the contained conventional assembly of test kit that detects by nucleic acid amplification.Described primer designs at the SNP site shown in the figure, and length is 18bp-21bp.Preferably, described primer is selected from a group that SEQ ID NO:1-24 forms, and more preferably, described primer is for having SEQ ID NO:25, single-basic extension (SBE) primer of sequence shown in the SEQ ID NO:26.
According to a further aspect in the invention, the primer that is used to predict the diabetes B susceptibility is provided, described primer is that described primer designs at the SNP site shown in the figure based on the special primer that is used for pcr amplification of the sequences Design of Figure 1B or Figure 1A, and length is 18bp-21bp.Preferably, described primer is selected from one group that SEQ ID NO:1-24 forms.According to a preferred embodiment of the present invention, primer of the present invention is SEQ ID NO:25, the single-basic extension shown in the SEQID NO:26 (SBE) primer.
In accordance with a further aspect of the present invention, provide SAC gene (soluble adenylate cyclase) to be used for the application of the diagnostic reagent of diabetes diagnosis as the diabetes tumor susceptibility gene in preparation, the nucleotide sequence of SAC gene is shown in SEQ ID NO:27.
Description of drawings
Figure 1A illustrates the nucleotide sequence of the SAC gene region at place, SNP of the present invention site (R).
Figure 1B is the complementary sequence of Figure 1A sequence
The catalyst structure domain of two predictions that Fig. 2 A comprises for the SACN end parts.
Fig. 2 B is the exon that SNP was positioned at of this patent protection.
Embodiment
Definition:
Single nucleotide polymorphism (SNP): mainly be meant on the genomic level by the caused dna sequence polymorphism of the variation of single Nucleotide.It is modal a kind of in human heritable variation, accounts for more than 90% of all known polymorphisms.
Microsatellite locus: is length that the tandem repetitive sequence (VNTR) of 2-6 Nucleotide calls little satellite (Microsatellite), microsatellite locus has two advantages the most outstanding: the one, and its frequency of occurrences is very high, be dispersed throughout whole genome, and, because short sequence is not selected on evolving, thereby variable repeating unit number of variations is very big on same site, and a site has nearly tens kinds allelotrope, information content height; The 2nd, the specificity single-copy sequence stability of STR both sides is high, can be used as the PCR primer that detects its polymorphism.With the round pcr operation, can realize the automatization large-scale operation
Gene type and gene frequency distribute: in the same population biology, the sequence analysis of phase isoallele nucleotide sequence is represented determining of the moiety of identical SNP site in Different Individual at this, is gene type.Gene frequency is meant in the same kind allelotrope of being studied, and the allelic proportion that changes just appears in the ratio that the allelotrope of desired appearance accounts for.
Disease susceptibility (diabetes susceptibility): the crowd experiences degree easily to disease.
Case-contrast association analysis: be a kind of a priori retrospective study.It is earlier to determine the respondent by morbid state, is divided into case and control group, and the difference by the genetic marker frequency of occurrences studied between case group relatively and control group obtains information related between this sign and disease.
Single-basic extension (SBE) reaction: it is meant and is lacking four kinds of dNTP, only existing under the situation of four kinds of ddNTP, Sequenase can add a ddNTP at 3 ' end of primer, but,, promptly come to an end after base is extended one and end so can not continue to extend because can not form phosphodiester bond.Only needing to detect this base gets final product.Claim little sequencing (Minisequencing) again.
Parameter linkage analysis and Non-Parametric Linkage Analysis Methods: calculate two chromosome maps between the gene apart from being linkage analysis according to the recombination fraction of gene, analyze with classified variable (discrete variable), measurement index is sorted out by a certain standard, counting, analyze then and be the parameter analysis, the analysis of carrying out with the result after the actual measurement is a Non-Parametric Linkage Analysis Methods
One of SAC genes encoding and the different adenylate cyclase of the typical adenylate cyclase of Mammals are positioned chromosomal 1q24.In human genome, be arranged in pac clone Z97876.(
http：//www.ncbi.nlm.nih.gov/entrez/query.fcgi？cmd＝Retrieve&db＝nucleotide&list?uids＝2582745&dopt＝GenBank)。It is a kind of information or prompting of diabetes B tumor susceptibility gene that prior art does not disclose any relevant SAC gene.
CAMP is an almost ubiquitous second signal molecule, signal can be transmitted to intracellular cAMP dependent protein PKA, GEFs.For a long time, only know that the generation of cAMP in Mammals is relevant by hormone, stride the product of film adenylate cyclase tmACs.The feature of these cyclases is membrane spaning domains that 12 predictions are arranged, and to the regulatory factor forskolin sensitivity of heterotrimeric G albumen and non-physiologic.
Soluble adenylate cyclase (SAC) be in the Mammals class very important adenylate cyclase.On molecular structure, on the biological chemistry all with by the G protein regulation, the adenylate cyclase of striding film has significant difference.SAC does not have membrane spaning domain, and insensitive to the adjusting albumen-G albumen of striding film adenylate cyclase tmACs of classics.Therefore, SAC is the cAMP signal transducting system as a kind of independent regulation and control in Mammals.Can be directly activated the albumen of purifying in vivo and at external SAC by carbanion.SAC is the form of dominant adenylate cyclase in mammiferous sperm the inside.It is directly activated the process that has caused the capacitation in fertilization process by carbanion.Immunolocalization research shows that also sAC has very abundant expression in its hetero-organization, and this illustrates that it may be in vivo a ubiquitous susceptor to HCO2-/CO2.
Predict the albumen of a 187kDa from SAC cDNA, and show that from the sequence that the 48kDa albumen of purifying obtains this 48kDa albumen obtains by proteic cutting from a 187kDa precursor molecule.The SAC of N end parts comprises the catalyst structure domain (Fig. 2 A) of two predictions.
In Mammals, nine different expression patterns stride the film adenylate cyclase, by the different regulation and control model of G albumen and the mediation of other signaling molecules, reply producing such as hormone and neurotransmitter.The adenylate cyclase of a solubility has been determined the approach of an important generation cAMP, may show that the second messenger can produce near the position in its effect away from film.The adenylic acid (AMP) ring of solubility looks like the gene of a single copy.These discoveries show obtaining by optionally shearing with the SAC that shortens of total length.Wherein No. 11 karyomit(e)s are sheared by selectivity exactly.The SNP of this patent protection is located in (Fig. 2 B) on this exon that is sheared.
2003 people such as Sun that deliver discover that SAC has activation to cftr gene in endothelial cell.The changing function of cftr gene can cause comprising the several conditions of diabetes.
Working in advance of this seminar shows, 1, all has the tumor susceptibility gene site of Han nationality in China diabetes B on 12,18 and No. 20 karyomit(e), wherein there are 4 zones (1p36,1p31,1q22 and 1q42-43) to show and diabetes B linked (this group forefathers make, and do not need document) on No. 1 karyomit(e).Shown in following embodiment, further the fine scanning result that this zone is carried out shows wherein have 3 zones (1p36.33-36.23,1q24.3-25.1 and 1q42.12-42.13) still to exist chain.
Have a plurality of public databases to store millions of SNP information at present, people can be in several ways, as with gene name, registration number, karyomit(e) number, functional class etc., searches.But, the SNP in these databases most just " candidates ", but not real SNP through verifying.They utilize computer to excavate out when a plurality of cloned sequences are compared, and wherein certainly exist a part of false positive SNP.In addition, these SNP great majority are the SNP that utilize Caucasian and Black people to check order and seek, and some is not necessarily identical for the distribution in Chinese population, and we utilize the diabetic subject and the normal control of Han People of North China, and SNP is sought in order-checking again.And utilize the SNP of the high frequency that we find in the northern Han nationality of China diabetic population to carry out gene type.
For seeking the diabetes B tumor susceptibility gene, the inventor chooses 34 candidate genes of diabetes B that are positioned at 1p36.23-36.33,1q24.3-25.1 and 1q42.12-42.13 zone according to the information that announce at American National information biology (National Center for Biotechnology Information) center, exon to these genes, Promotor district 2kb, and check order SNP in the examination Han People of North China of the zone of the intron that closes on.And the SNP of part high frequency wherein carried out gene type, (comprise direct SBE reflection, Snapshot by the SBE reaction
TMTest kit, Snupe
TMTest kit), enzyme is cut, and methods such as sequencing are carried out somatotype and case-contrast association analysis to it in case group and control group.
Go through as following examples, in the SNP site of selected 124 high frequencies, choose 11 sites in the SAC gene and carried out gene type, find that this site is relevant with diabetes, lay respectively at a SNP site (Y at 15 places of ride on Bus No. 11 exon, be T/C), numbering among the NCBI is rs203849, the difference that its gene frequency is distributed in case group and the control group has statistical significance (P＜0.05), point out this SNP site relevant with diabetes B, further reach a conclusion, its place gene SAC gene is the tumor susceptibility gene of Chinese northerner's diabetes B.
Therefore, one aspect of the present invention relates to the application of diabetes tumor susceptibility gene SAC gene in the prediction diabetes susceptibility.Based on the SAC gene, can obtain various diagnostic reagents and test kit to be used to predict diabetes susceptibility.
SAC place genome sequence is shown in SEQ ID NO:27, total length is 104,424bp, disclosed SNP site (Y) is between the 33550-34349 position of this sequence, this regional nucleotide sequence is shown in Figure 1A, and Y is the SNP site among the figure, and it represents base T/C polymorphism, promptly this site can be T, also can be T.This regional complementary sequence is shown in Figure 1B, and R represents the complementary base in SNP of the present invention site among the figure, and it represents base A/G.
The invention still further relates to the primer that is used to predict diabetes susceptibility.Preferably, described primer designs based on the sequence of Figure 1B, and thus, the product order-checking behind the pcr amplification can directly record the SNP site.Certainly, primer of the present invention also can be based on the sequences Design of Figure 1A, and the order-checking of the product behind the pcr amplification obtains the complementary base of SNP like this.Preferably, primer of the present invention has the sequence shown in the SEQ ID NO:1-26, particularly preferably is the SBE primer shown in the SEQ ID NO:25SEQ ID NO:26.Following table 1 shows some combinations of primer of the present invention, the product size that the melting temperature(Tm) of primer (Tm) and these combinations obtain for example.It will be appreciated by those skilled in the art that primer of the present invention is not limited to these primer of listing and combinations thereof.
Table 1
| ??SEQ?ID ????NO： | Primer sequence and Tm | The product size |
| ????1 ????2 | Justice is arranged: ccaacgggtagagaaaatcc (60.23 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????249bp |
| ????1 ????3 | Justice is arranged: ccaacgggtagagaaaatcc (60.23 ℃) antisense: ttgcagaaagaaagctggag (60.18 ℃) | ????241bp |
| ????4 ????5 | Justice is arranged: cacaaatcttgtctcccctg (60.01 ℃) antisense: gggctcatgtctcactcatt (59.57 ℃) | ????204bp |
| ????6 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) | ????222bp |
| ????7 | Antisense: TCGTGTCTCACAGTGTGTCC (60.28 ℃) | |
| ????8 ????2 | Justice is arranged: aaaatcctttcccacccttt (60.45 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????236bp |
| ????6 ????2 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????277bp |
| ????6 ????3 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) antisense: ttgcagaaagaaagctggag (60.18 ℃) | ????269bp |
| ????6 ????9 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) antisense: tttgcagaaagaaagctgga (60.56 ℃) | ????270bp |
| ????8 ????5 | Justice is arranged: aaaatcctttcccacccttt (60.45 ℃) antisense: gggctcatgtctcactcatt (59.57 ℃) | ????290bp |
| ????10 ????11 | Justice is arranged: tgaggcataagtagggaggg (60.90 ℃) antisense: GGATACAGTTctggtgcagg (60.04 ℃) | ????266bp |
| ????6 ????5 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) antisense: gggctcatgtctcactcatt (59.57 ℃) | ????331bp |
| ????12 ????3 | Justice is arranged: gcagggaacaggaaagaaag (60.67 ℃) antisense: ttgcagaaagaaagctggag (59.6 ℃) | ????349bp |
| ????12 ????7 | Justice is arranged: gcagggaacaggaaagaaag (60.67 ℃) antisense: TCGTGTCTCACAGTGTGTCC (60.28 ℃) | ????302bp |
| ????6 ????13 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) antisense: ctcatttttgtgcttcctcc (59.19 ℃) | ????317bp |
| ????6 ????14 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) antisense: agggctcatgtctcactcat (59.15 ℃) | ????332bp |
| ????12 ????2 | Justice is arranged: gcagggaacaggaaagaaag (60.67 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????357bp |
| ????10 ????2 | Justice is arranged: tgaggcataagtagggaggg (60.90 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????380bp |
| ????10 ????3 | Justice is arranged: tgaggcataagtagggaggg (60.90 ℃) antisense: ttgcagaaagaaagctggag (60.18 ℃) | ????372bp |
| ????15 ????2 | Justice is arranged: tttgaggcataagtagggagg (60.01 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????382bp |
| ????16 ????2 | Justice is arranged: aggcataagtagggagggc (59.98 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????378bp |
| ????12 ????5 | Justice is arranged: gcagggaacaggaaagaaag (60.67 ℃) antisense: gggctcatgtctcactcatt (59.57 ℃) | ????411bp |
| ????6 ????17 | Justice is arranged: ggccatgtagaaatgccata (60.23 ℃) antisense: atgcacactctgcaagcat (59.93 ℃) | ????403bp |
| ????10 ????5 | Justice is arranged: tgaggcataagtagggaggg (60.90 ℃) antisense: gggctcatgtctcactcatt (59.57 ℃) | ????434bp |
| ????15 | Justice is arranged: tttgaggcataagtagggagg (60.01 ℃) | ????436bp |
| ????5 | Antisense: gggctcatgtctcactcatt (59.57 ℃) | |
| ????16 ????5 | Justice is arranged: aggcataagtagggagggc (59.98 ℃) antisense: gggctcatgtctcactcatt (59.57 ℃) | ????432bp |
| ????12 ????18 | Justice is arranged: gcagggaacaggaaagaaag (60.67 ℃) antisense: acactctgcaagcattgagg (60.94 ℃) | ????479bp |
| ????12 ????19 | Justice is arranged: gcagggaacaggaaagaaag (60.67 ℃) antisense: cactctgcaagcattgagg (60.05 ℃) | ????478bp |
| ????12 ????17 | Justice is arranged: gcagggaacaggaaagaaag (60.67 ℃) antisense: atgcacactctgcaagcat (59.93 ℃) | ????483bp |
| ????10 ????24 | Justice is arranged: tgaggcataagtagggaggg (60.90 ℃) antisense: taaagtttctgagggcaggg (61.05 ℃) | ????451bp |
| ????16 ????18 | Justice is arranged: aggcataagtagggagggc (59.98 ℃) antisense: acactctgcaagcattgagg (60.94 ℃) | ????500bp |
| ????10 ????18 | Justice is arranged: tgaggcataagtagggaggg (60.90 ℃) antisense: acactctgcaagcattgagg (60.94 ℃) | ????502bp |
| ????10 ????19 | Justice is arranged: tgaggcataagtagggaggg (60.67 ℃) antisense: cactctgcaagcattgagg (60.05 ℃) | ????501bp |
| ????15 ????18 | Justice is arranged: tttgaggcataagtagggagg (60.01 ℃) antisense: acactctgcaagcattgagg (60.94 ℃) | ????504bp |
| ????16 ????18 | Justice is arranged: aggcataagtagggagggc (59.98 ℃) antisense: acactctgcaagcattgagg (60.94 ℃) | ????500bp |
| ????10 ????17 | Justice is arranged: tgaggcataagtagggaggg (60.90 ℃) antisense: atgcacactctgcaagcat (59.93 ℃) | ????506bp |
| ????20 ????2 | Justice is arranged: gttgctgtctctctccctca (60.04 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????565bp |
| ????21 ????2 | Justice is arranged: agctgtggttgctgtctctc (60.11 ℃) antisense: tgctgtgtttgcagaaagaa (60.08 ℃) | ????572bp |
| ????20 ????3 | Justice is arranged: gttgctgtctctctccctca (60.04 ℃) antisense: ttgcagaaagaaagctggag (60.18 ℃) | ????557bp |
| ????21 ????3 | Justice is arranged: agctgtggttgctgtctctc (60.11 ℃) antisense: ttgcagaaagaaagctggag (60.18 ℃) | ????564bp |
| ????22 ????23 | Justice is arranged: ctgacccttttgaggcataa (59.60 ℃) antisense: atatagcctcccactgctcc (59.99 ℃) | ????580bp |
The invention further relates to the test kit that comprises one or more primer of the present invention, this test kit is used to detect the susceptibility of diabetes.Except primer of the present invention, described test kit also comprises the utilization pcr amplification and the conventional assembly of the test kit that detects, reagent, damping fluid etc., and those skilled in the art are familiar with these conventional assembly and detection methods.
Further describe the present invention hereinafter with reference to embodiment.
The Fine Mapping of embodiment 1 Han People of North China diabetes B tumor susceptibility gene
1, the collection of diabetes B family
Collect and satisfy the following diabetes B family that requires in the Han People of North China:
1) in continuous 2 generations or occur the diabetes B patient more than 2 generations in the family, in per generation, have a patient, a normal people at least.
2) diabetic subject should make a definite diagnosis in regular hospital, to insulin insensitivity person (except type 1 diabetes).Selected contrast Individual Age should be in (to get rid of as yet the not family member of morbidity as far as possible) more than 35 years old.
3) except that diabetes, other significant organic disease of nonjoinder is as hypertension, coronary heart disease (except complication that diabetes caused) etc.
Should guarantee that before gathering family all family members all understand the blood sampling purpose, promptly have right to know, blood sample to provide the people after having understood all situations,, go up signature, the investigation with other personal considerations of could implementing to draw blood at " Informed Consent Form " if agree.If disagree with, then respect its individual opinion.The data of collecting is holded in close confidence, externally do not announce all data such as name, age, disease of blood supply member.
To each member of selected family, except that the diabetes B patient who has clarified a diagnosis, (whether Oral Glucose Tolerance Test OGTT), can be used as normal control to confirm each member all should to carry out the oral glucose carbohydrate tolerance test.OGTT process of the test: extract the venous blood of venous blood and oral 75g glucose (finishing off in 5 minutes) on an empty stomach back 30 minutes, 60 minutes, 120 minutes and 180 minutes, observe the dynamic change situation of blood sugar concentration.In addition, write down each individual generalized case, comprise sex, date of birth, native place, age of onset, height, body weight, heart rate, breathing, blood pressure, medicining condition, have or not complication and blood fat, project such as blood electrolyte, go special examined in case of necessity, be associated with the family of diseases such as hypertension, heart trouble, atherosclerosis with eliminating.
The diagnosis of diabetes B is carried out in strict accordance with the standard that WHO issued in 1985.That is: fasting blood glucose concn 〉=7.8mmol/L or 2 hours after the meal blood sugar 〉=11.1mmol/L are diabetes.The judging criterion of OGTT is: back 2 hours blood glucose concentration＜7.8mmol/L of clothes sugar are for normal, and 〉=11.1mmol/L is diabetes, between 7.8-11.1mmol/L be impaired glucose tolerance (impaired glucose tolerance, IGT).
Collect 60 diabetes B familys that meet above condition altogether, the member amounts to 367 people.Diabetes B patient 180 examples wherein, normal people's 171 examples, IGT patient's 16 examples.These familys are respectively from the crowd of Han nationality on ground such as Beijing, Shandong, Hebei, the Inner Mongol, Henan.Draw the pedigree chart of all familys, and each family and family member are numbered, this numbers with DNA warehouse-in unanimity.In collected family, 15% (9/60) is three generations's family, 85% (51/60) be two generation family.The male sex is 83 people among the patient, and the women is 97 people; IGT person 16 people.Family member's mean age is 50.03 years old, and its distribution situation (dividing ill and normal) sees Table 2:
Table 2 diabetes B family member age composition
| Age bracket | The case group | Normal group | ???IGT | Amount to |
| ????＜30 | ????10 | ????17 | ????2 | ????29 |
| ????31-40 | ????26 | ????45 | ????2 | ????73 |
| ????41-50 | ????51 | ????56 | ????7 | ????115 |
| ????51-65 | ????42 | ????26 | ????3 | ????70 |
| ????＞65 | ????51 | ????27 | ????2 | ????80 |
| Amount to | ????180 | ????171 | ????16 | ????367 |
The peripheral blood sample of getting all each members of family is standby.
2, the little satellite fragment of pcr amplification, gene type
Ordinary method is extracted the genomic dna in the above-mentioned blood sample, and the DNA after the extraction all is dissolved in the TE damping fluid, indicates data such as the affiliated family of sample, numbering, and-20 ℃ of preservations are stand-by.
, distribution comparatively uniform microsatellite locus higher at full genome scanning hot spot (1p36,1p31,1p12,1q22,1q42-43 district, 20p12,20q13 district, 12p12 district and 18q23 district) selection heterozygosity in the past carries out second wheel scan.60 sites have been selected altogether, wherein: interior 34 of 5 positive regions of No. 1 karyomit(e), mean density 3.2cM; 4 of No. 12 karyomit(e)s, mean density 2.2cM; 4 of No. 18 karyomit(e)s, mean density 1.9cM; On No. 20 karyomit(e)s in 3 zones 18, mean density 2.6cM.The minimum heterozygosity of these microsatellite locus is 0.64, is up to 0.88, mean value 0.748.Gained (under " Human PhysicalMapping Project " hurdle) is searched from http://www-genome.wi.mit.edu in the genetics position of part microsatellite locus, and part obtains on the data at the human polymorphism center of French Genethon.In 60 used microsatellite locus, 16 existing primers in the Version2.0 of ABI company test kit, 46 need newly design synthetic primer.In the new a pair of primer of synthetic one with fluorescent substance FAM or HEX mark.The size and the possible reasonable grouping situation of all primers comprehensive consideration pcr amplified fragment length when synthetic are determined fluorescently-labeled color.React used primer sequence Microsatellite Markers Data Set referring to French Genethon genetic map.Each microsatellite locus expanding fragment length and primer information see Table 3.
The magnitude range and the mark fluorescent of 60 microsatellite locus of table 3
Site title clip size (bp) mark fluorescent site title clip size (bp) mark fluorescent
D1S243????142-170?????????HEX????D1S2709?????191-197?????????FAM
D1S468????173-191?????????HEX????D1S2800?????195-225?????????FAM
D1S2845???193-233?????????FAM????D1S235??????175-195?????????FAM
D1S214????122-152?????????NED????D1S2850?????145-153?????????FAM
D1S2663???183-205?????????FAM????D12S1625????264-280?????????FAM
D1S472????228-244?????????FAM????D12S77??????163-193?????????FAM
D1S2892???93-129??????????FAM????D12S336?????117-135?????????NED
D1S2722???195-223?????????FAM????D12S89??????254-288?????????HEX
D1S463????223-233?????????HEX????D18S465?????233-251?????????HEX
D1S211????170-198?????????HEX????D18S61??????213-243?????????NED
D1S2627???265-279?????????FAM????D18S1125????268-286?????????FAM
D1S2868???210-224?????????FAM????D18S488?????239-264?????????HEX
D1S497????250-278?????????FAM????D20S906?????229-247?????????FAM
D1S206????208-226?????????NED????D20S842?????156-180?????????HEX
D1S495????138-164?????????FAM????D20S889??????93-129?????????FAM
D1S2707????137-159?????FAM????????D20S849????214-236?????FAM
D1S2878????152-178?????NED????????D20S95?????82-100??????FAM
D1S196?????322-338?????HEX????????D20S892????205-223?????FAM
D1S2815????210-237?????FAM????????D20S115????238-250?????NED
D1S218?????266-286?????NED????????D20S851????128-150?????FAM
D1S466?????155-175?????FAM????????D20S901????260-268?????FAM
D1S2692????187-217?????HEX????????D20S186????121-143?????HEX
D1S245?????235-253?????FAM????????D20S852????152-176?????HEX
D1S205?????94-112??????FAM????????D20S112????217-241?????FAM
D1S425?????336-360?????NED????????D20S912????267-283?????FAM
D1S419?????162-194?????FAM????????D20S857????204-220?????FAM
D1S2860????168-184?????FAM????????D20S840????141-165?????FAM
D1S2880????113-135?????FAM????????D20S120????213-241?????FAM
D1S213?????107-133?????NED????????D20S100????213-239?????HEX
D1S2833????92-108??????FAM????????D20S102????169-177?????FAM
Behind the pcr amplification, on 377 electrophoresis apparatuses (ABI company), carry out electrophoresis, with 377 electrophoresis image collection software (ABI Prism
TM377-96 Collection or ABI Prism
TM377XL Collection) collect the result, GENEHUNTER2.0 software (Massachusetts Institute Technology's hereditary system is write, from
Http:// cmag.cit.nih.govOn can freely download) go up computing, calculate relevant site and chain P value, the Z value of phenotype.The result is presented in 10 zones being studied has 3 zones to continue to demonstrate and the diabetes Evidence for linkage, as shown in table 4:
Hereditary position, P value and the Z value in meaningful site in 3 positive regions of table 4
The site title is added up P primary system meter Z value apart from the p end-to-end distance from (cM) cytogenetic location
D1S243????0.0?????????????????1p36.33???????0.00834?????1.653
D1S468????6.2?????????????????1p36.33???????0.0015??????2.135
D1S2845???11.1????????????????1p36.32???????0.033???????1.292
D1S214????16.4????????????????1p36.31???????0.0025??????2.005
D1S2663???16.9????????????????1p36.23???????0.00205?????1.996
D1S2815???193.8???????????????1q24.3????????0.00126?????2.17
D1S218????196.5???????????????1q25.1????????0.043???????1.2
D1S2800???256.2?????1q42.12?????????0.0128????1.579
D15235????258.7?????1q42.13?????????0.0547????1.363
As can be seen from the above table, the positive site of 1p36.33-36.23 district meaningful (P＜0.05) is maximum, has 5, and minimum P value is 0.0015, and 2.135,5 sites of Z value are distributed in the zone that reaches 16.9cM.1q24.3-25.1 there are 2 sites in the district, 1q42.12-42.13 the district has 1 site to satisfy the standard of P＜0.05, therefore though the P value of D1S235 is a little more than 0.05 in addition, its Z value has reached statistics dividing value (Z＞1.36), can think that this site and diabetes still have linkage relationship.Fine Mapping has been distinguished to the narrow range of 2.7cM (D1S2815-D1S218) and 2.5cM (D1S2800-D1S235) in these two zones.Noticeable is in the 1p36.33-36.23 district, and continuous 5 sites the P value all occurred less than 0.05 situation, so next step selects this regional cloning tumor susceptibility gene.
The correlative study of SNP in the evaluation of embodiment 22 type diabetes tumor susceptibility gene SAC and this gene
1, the collection of Han People of North China diabetes B patient and normal control sample
Normal group and diabetes B group crowd peripheral blood sample all pick up from the outpatient service of Endocrinology Department of BJ Union Hospital.The sample source is the northern area of China, comprises ground such as Beijing, Shandong, Hebei, Inner Mongolia Autonomous Region, based on Beijing.Diabetes can be distributes, and also can be member's (but have only in each family this moment a patient selected usually, the member without any genetic connection in the same family can select more than) of diabetic pedigree; Normal control requires the three generations of its family with the interior diabetic subject of not having (comprising type i diabetes) from normal population, and control group and ill group of age and sex are complementary.
The diabetes B diagnosis is with embodiment 1.Each selected member record generalized case, comprise sex, date of birth, native place, age of onset, height, body weight, heart rate, breathing, blood pressure, medicining condition, have or not complication etc., each member is checked projects such as blood fat, blood electrolyte, capable in case of necessity special examined is associated with diseases such as hypertension, heart trouble, atherosclerosis with eliminating.Each selected member should go up signature at " Informed Consent Form ".
Collect 325 parts of samples altogether, wherein the case group is 173 parts, 152 parts of control groups.Two groups in sex, be complementary on the age, and diabetic subject's mean age is 51.99 years old, and the mean age during the normal control sampling is 48.8 years old.In all members, men and women's ratio is 169:156, the case group male sex 92 people, women 81 people; The control group male sex 77 people, women 75 people.Two group memberships' age structure situation is as follows:
Ill group of table 5 and control group member's age composition
| Age bracket | The case group | Control group |
| ????＜30 | ????2 | ????4 |
| ????30-39 | ????12 | ????18 |
| ????40-49 | ????30 | ????54 |
| ????50-65 | ????91 | ????62 |
| ????＞65 | ????38 | ????14 |
| Amount to | ????173 | ????152 |
2, be used for the selection in the SNP site of gene type in the definite and candidate gene of candidate gene
Based on the result of embodiment 1, promptly karyomit(e) 1p36.33-36.23 zone is linked with diabetes B, utilize bioinformatics method from the NCBI snp database (
Www.ncbi.nlm.nih.gov/SNP) in select and be positioned near the promotor district 2kb that this zone or it 37 and glucose metabolism genes involved are measured gene, exon and be close to include subarea and 3 ' non-translational region.And the snp of wherein 80 high frequencies carried out gene type, described 34 candidate genes are as follows:
(1) CASPASE-9 is positioned at chromosomal 1p36.3-p36.1, is caspase family member's halfcystine arginine proteolytic enzyme, and the proteic sequential activation of caspase plays important effect in the execute phase of apoptosis.Caspase albumen exists with the precursor protein form of non-activity, and by producing two subunits in conservative arginine residues place fracture, these two subunits are combined into activated proteolytic enzyme.
(2) CDC2L2 genes encoding p34Cdc2 protein kinase family member is positioned at 1p36.3.This kinases family member plays a part crucial to eukaryotic cell cycle regulating.
(3) glucose phosphate dehydrogenase (PGD) is second desaturase in the pentose phosphate alternative pathway, is positioned at the 1p36.3-p36.13 of human chromosome.
(4) PRKCZ is protein kinase C ζ member, is positioned at chromosomal 1p36.33-p36.2 position.Be Serine, the ζ member in the Serineprotein kinase family, it participates in several cellular process,
(5) one of SAC genes encoding and the typical different adenylate cyclase of Mammals are positioned at chromosomal 1q24.
(6) Urotensin II gene is positioned at karyomit(e) 1p36, and the sophisticated polypeptide of encoding has active ring 12 peptides, has very high conservative property from seven cheek eels to the mankind.
(7) the GNB1 gene is positioned at karyomit(e) 1p36.33, accepts to transmit signal between molecule and the effector molecule at signal, is made of this genes encoding beta subunit three different subunits.
(8) the GPR52 gene is positioned at karyomit(e) 1q24, the receptor family member of G protein coupling.
(9) amiloride susceptibility sodium-ion channel δ subunit (dNaCh, SCNN1D) gene: be arranged in 1p36.32 district NT 002209, coded product belongs to non-voltage-sensitive type channel protein, can be suppressed by the diuretic(s) amiloride, ionic electrodiffusion in the mediation chamber is present on the film with the tetrameric form of allos.
(10) acetyl-CoA thioester hydrolase (HBACH) gene: be arranged in 1p36.23 district NT 002530.Coded product belongs to one of acetylcoenzyme family member, the CoA thioesters of hydrolyzable palmitinic acid CoA and other longer chain fatty acid.
(11) Urotensin II: be arranged in 1p36.23 district NT 002530.At present its protein function is known little, but known its conservative property is very high.A g protein coupled receptor GPR14 can be used as its acceptor.
(12) DJ-1 (rna binding protein adjusting subunit): be arranged in 1p36.23 district NT 002163.
(13) 5,10-Methylene tetrahydrofolate reductase (MTHFR) genes: be arranged in 1p36.21 district AL354994 clone.5, the 10-Methylene tetrahydrofolate reductase participates in folic acid metabolism, is the key enzyme of the process that methylates again of homocysteine folic acid dependence, with homodimer form performance catalytic activity, regulated by the other structure of S-ademetionine.
(14) chloride channel B (CLCNKB) gene: be positioned at 1p36.13 district bA254I4.00143 (long 47068bp, belong to unfinished sequence) in, the valtage-gated type chloride channel protein Type B of encoding is mainly expressed in kidney, and it and A type have 94% homology.Chloride channel can participate in regulating cell volume, membrane potential stability, signal conduction and transepithelial transhipment etc.(15) TNFSF4 is positioned at chromosomal 1q25, the individuality of a tumor necrosis factor receptor super family of coding.
(16) TNFSF6 is positioned at chromosomal 1q23, the individuality of a tumor necrosis factor receptor super family of coding.
(17) SLC19A2 is positioned at chromosomal 1q23.3, and the translocator of coding VITAMIN b1 belongs to the member that folic acid is transported superfamily.
(18) CDC42BPA is called PK428 again, is positioned at karyomit(e) 1q42.11, and is similar with the protein kinase that myotonia atrophica is relevant, Serine, and Serineprotein kinase, similar with the protein kinase that cAMP relies on.
(20) KCNK1 is positioned at chromosomal 1q42-q43, the member of a potassium-channel proteins superfamily of this genes encoding, include 2 p structural domains that form porin, the product of this gene seems not to be a functional passage, and he needs other proteic participation just to have activity.
(21) ATP2B4 is positioned at chromosomal 1q25-q32, a plasma membrane calcium ion of this genes encoding pump.
(22) CACYBP is positioned at chromosomal 1q24-q25, a calcium binding protein of this genes encoding conjugated protein, and this proteic bonded effect is not clear.
(23) chloride channel A (CLCNKA) gene is positioned among the 1p36.13 district bA254I4.00143 (long 47068bp belongs to unfinished sequence), and the valtage-gated type chloride channel protein A type of encoding is mainly expressed in kidney.
(24) ENO1 is positioned at chromosomal 1p36.3-p36.2, in 3 Hydratase, phosphoenolpyruvate isomerases in this genes encoding Mammals one, its alpha Hydratase, phosphoenolpyruvate of encoding, a homodimer lyoenzyme.
(25) DFFA is positioned at chromosomal 1p36.3-p36.2, a dna fragmentation factor D of this genes encoding FF, and this is that an allodiploid albumen comprises DFFB and two subunits of DFFA.
(26) G albumen gamma 4 albumen (GNG4) are components in the heterotrimeric G protein complexes, trimer protein from the acceptor birth canal signal of G protein coupling to intracellular effector.
(27) ICMT isopentyl halfcystine carbonyl methyltransgerase is positioned at chromosomal 1p36.21, proteic transferring enzyme of posttranslational modification of this genes encoding.
(28) RE2 is the acceptor of G protein coupling, is positioned at chromosomal 1q23.2, and this gene is the G protein coupling receptor of rhodopsin family, assists regulation and control to attack and feed.
(29) PKLR is the carbohydrate-splitting enzyme of the L type of liver pyruvate kinase, is positioned at chromosomal 1q23.2, and phosphoenolpyruvic acid is transformed into pyruvic acid, and generates ATP.
(30) ALPL is a kind of non-tissue-specific alkaline phosphatase, is positioned at chromosomal 1p36.1-p34, and at liver, bone, kidney all have distribution.Physiological function is unknown now accurately.
(31) PLA2G2D is phosphoesterase A2, and the IID group is positioned at chromosomal 1p36.12, and perhaps the sn-2 ester bond of preferential hydration's phosphatide has important function in the process that infects.
(32) CA14 is in the carbonyl dehydratase family one, is positioned at chromosomal 1q21, and the reversibility aquation of catalysis carbonic acid gas participates in several different physiological processs.
(33) CA6 is in the carbonyl dehydratase family one, is positioned at chromosomal 1p36.2, and the reversibility aquation of catalysis carbonic acid gas is mainly found in sialisterium the inside.
(34) PANK4 is the member of pantothenate kinases family, is positioned at chromosomal 1p36.23, and the biology of catalysis coenzyme A contains to become in bacterium and Mammals.And be subjected to the feedback regulation of coenzyme A.
Selected 80 SNP sites that are used for gene type are as shown in table 6.
| The gene title | The segment name | The site | The position | The Snp type | The site function | ????P?value |
| Gene frequency | ||||||
| ????CDC2L2 | ??L11N1 | ????SNP1 | ??Intron11 | ????A/G | ????Intron | ????0.181 |
| ????SNP2 | ??Intron11 | ????T/C | ????Intron | ????0.942 | ||
| ????SNP3 | ??Intron12 | ????T/C | ????Intron | ????0.158 | ||
| ????SNP4 | ??Intron12 | ????T/C | ????Intron | ????0.746 | ||
| ??L13N1 | ????SNP1 | ??Intron17 | ????A/G | ????Intron | ????0.331 | |
| ????SNP2 | ??Exon18 | ????C/T | ????Intron | ????0.234 | ||
| ????SNP3 | ??Exon18 | ????C/T | ????Intron | ????0.217 | ||
| ????SNP4 | ??Exon18 | ????C/T | ????Intron | ????0.280 | ||
| ????SNP5 | ??Exon18 | ????A/G | ????Intron | ????0.670 | ||
| ??L5N1 | ????SNP1 | ??Exon4 | ????T/C | ????Tyr→Arg | ????0.493 | |
| ????SNP2 | ??Splicing ????site | ????A/G | ????Splicing ????site | ????0.421 | ||
| ??L6N1 | ?DELETION | ??Intron5 | ????A/ | ????Deletion | ????0.269 | |
| ??L9N1 | ????SNP1 | ??Splicing ????site | ????A/G | ????Splicing ????site | ????0.024 | |
| ????SNP2 | ??Intron9 | ????C/G | ????Intron | ????0.035 | ||
| ????SNP3 | ??Intron9 | ????A/T | ????Intron | ????0.112 | ||
| ????GNG4 | ??L3N1 | ????SNP1 | ??Intron1 | ????G/A | ????Intron | ????0.477 |
| ????SNP2 | ??Intron1 | ????C/A | ????Intron | ????0.865 | ||
| ????SNP3 | ??Intron1 | ????G/A | ????Intron | ????0.606 | ||
| ????SNP4 | ??Intron1 | ????G/C | ????Intron | ????1.000 | ||
| ????SNP5 | ??Exon2 | ????G/A | ????Ala→Ala | ????0.863 | ||
| ????PGD | ??L13N2 | ????SNP1 | ??Exon12 | ????G/A | ????Ser→Ser | ????0.073 |
| ????SNP2 | ??Intron10 | ????G/A | ????Splicing ????site | ????0.021 | ||
| ????SNP3 | ??Intron | ????G/C | ????Intron | ????0.539 | ||
| ??L1N2 | ????SNP1 | ??Promotor | ????A/T | ????Intron | ????0.496 | |
| ????SNP2 | ??Promotor | ????C/T | ????Intron | ????0.226 | ||
| ????SNP3 | ??Promotor | ????A/G | ????Intron | ????0.247 | ||
| ????SAC | ??L1N2 | ????SNP1 | ??Intron12 | ????A/C | ????Intron | ????0.017 |
| ????SNP2 | ??Intron12 | ????C/T | ????Intron | ????0.137 | ||
| ????SNP3 | ??Intron12 | ????G/C | ????Intron | ????0.011 | ||
| ????SNP4 | ??Intron12 | ????A/T | ????Intron | ????0.034 | ||
| ??L6N1 | ????SNP1 | ??Intron16 | ????A/G | ????Intron | ????0.126 | |
| ????SNP2 | ??Exon17 | ????C/T | ????Phe→Ser | ????0.832 | ||
| ????SNP3 | ??Exon17 | ????G/A | ????Val→Ile | ????0.739 |
| ??L10N2 | ????SNP1 | ??Exon11 | ????T/C | ???Gly→Gly | ????0.003 | |
| ??L26N1 | ????SNP1 | ??Intron28 | ????A/C | ???Intron | ????0.202 | |
| ??L17N1 | ????SNP1 | ??Intron18 | ????G/A | ???Intron | ????0.243 | |
| ????SNP2 | ??Intron18 | ????C/T | ???Intron | ????0.595 | ||
| ???ALPL | ??L8N1 | ????SNP1 | ??Exon7 | ????T/C | ???Tyr→His | ????0.685 |
| ??L9N1 | ????SNP1 | ??Intron8 | ????C/T | ???Intron | ????0.474 | |
| ????SNP2 | ??Intron8 | ????G/T | ???Intron | ????0.360 | ||
| ????SNP3 | ??Intron8 | ????G/A | ???Intron | ????0.254 | ||
| ????SNP4 | ??Intron8 | ????C/T | ???Intron | ????0.528 | ||
| ???CASP9 | ??L3N1 | ????SNP1 | ??Intron2 | ????A/T | ???Intron | ????0.878 |
| ????SNP2 | ??Intron2 | ????C/T | ???Intron | ????0.829 | ||
| ??L2N4 | ????SNP3 | ??Intron1 | ????G/T | ???Intron | ????0.358 | |
| ??L8N1 | ????SNP4 | ??Intron7 | ????G/A | ???Intron | ????0.386 | |
| ??L9N1 | ????SNP5 | ??Exon8 | ????T/C | ???Phe→Phe | ????0.256 | |
| ??L4N1 | ????SNP6 | ??Intron8 | ????A/G | ???Intron | ????0.795 | |
| ??L2N4 | ????SNP7 | ??Intron1 | ????A/C | ???Intron | ????0.014 | |
| ???SCNN1D | ??L1N1 | ????SNP1 | ??Exon13 | ????A/G | ???Arg→Gly | ????0.741 |
| ??L1N3 | ????SNP2 | ??Intron10 | ????C/T | ???Intron | ????0.157 | |
| ???INSRR | ??L7N4 | ????SNP1 | ??Intron13 | ????G/A | ???Intron | ????0.106 |
| ??L1N2 | ????SNP2 | ??Promotor | ????G/T | ???Intron | ????0.437 | |
| ???KCNJ9 | ??L4N4 | ????SNP1 | ??Exon3 | ????C/T | ???Intron | ????0.280 |
| ???ATP2B4 | ??L13N1 | ????SNP1 | ??Exon12 | ????C/T | ???Asn→Asn | ????0.513 |
| ????SNP2 | ??Intron11 | ????C/T | ???Intron | ????0.749 | ||
| ??L17N1 | ????SNP1 | ??Intron16 | ????C/T | ???Intron | ????0.387 | |
| ??L6N1 | ????SNP1 | ??Intron5 | ????C/T | ???Intron | ????0.979 | |
| ???PK428 | ??L4N1 | ????SNP1 | ??Intron4 | ????C/T | ???Intron | ????0.171 |
| ????SNP2 | ??Intron5 | ????C/T | ???Intron | ????0.065 | ||
| ???TNFSF6 | ??L3N1 | ????SNP1 | ??Promotor | ????C/T | ???Intron | ????0.104 |
| ???CACYBP | ??L6N2 | ????SNP1 | ??3’UTR | ????C/T | ???Intron | ????0.600 |
| ???SLC19A2 | ??L1N1 | ????SNP1 | ??Promotor | ????A/G | ???Intron | ????0.943 |
| ???MTHFR | ??L6N3 | ????SNP1 | ??Intron4 | ????A/C | ???Intron | ????0.399 |
| ????SNP1 | ??Exon6 | ????A/C | ???Glu→Ala | ????0.595 | ||
| ??L4N1 | ????SNP1 | ??Intron3 | ????A/G | ???Intron | ????0.979 | |
| ????SNP2 | ??Intron2 | ????C/T | ???Intron | ????0.570 | ||
| ???PANK4 | ??L4N2 | ????SNP1 | ??Intron3 | ????C/T | ???Intron | ????0.304 |
| ??L1N1 | ????SNP1 | ??Promotor | ????C/T | ???Intron | ????0.487 | |
| ??L9N1 | ????SNP1 | ??Exon13 | ????C/T | ???Val→Ala | ????0.063 | |
| ????SNP2 | ??Intron13 | ????A/G | ???Intron | ????0.537 | ||
| ??L8N2 | ????SNP1 | ??Intron12 | ????C/T | ???Intron | ????0.962 | |
| ??L11N3 | ????SNP1 | ??Exon18 | ????A/G | ???Gln→Arg | ????0.609 | |
| ???CA6 | ??L3N1 | ????SNP1 | ??Exon1 | ????C/T | ???Intron | ????0.656 |
| ??L3N1 | ????SNP2 | ??Exon2 | ????C/T | ???Thr→Met | ????0.971 | |
| ??L3N1 | ????SNP3 | ??Exon2 | ????A/C | ???Met→Leu | ????0.780 |
| ??L3N1 | ????SNP4 | ??Exon2 | ????G/C | ?Gly→Ala | ????0.957 | |
| ??L3N1 | ????SNP5 | ??Exon2 | ????G/C | ?Gly→Gly | ????0.641 | |
| ??L5N1 | ????SNP1 | ??Exon4 | ????A/G | ?Gly→Ser | ????0.501 | |
| ??L9N1 | ????SNP1 | ??Exon7 | ????C/T | ?Asn→Asn | ????0.641 |
3, SNP locus gene phenotypic analysis
The main somatotype that adopts 3 kinds of methods to carry out SNP: length multiplicity single-basic extension (LengthMultiplexed Single Base Extension, LM-SBE) reaction, the SnaPshot method, restriction fragment length polymorphism (Restrictive Fragment Length Polymorphism, RFLP-PCR) and sequencing and typing.
1) .LM-SBE reaction carrying out SNP somatotype
1.1) design of primers and synthetic: at 3 primers of each SNP site design in above-mentioned 23 SNP sites, wherein 2 is the PCR primer, is used to increase comprise one section sequence in SNP site, and other one is the SBE primer, is used for single base extension.The PCR primer is by the online design of Primer 3.0 programs, and expanding fragment length is 150～300bp.
SBE design of primers principle: primer will be positioned at 5 of SNP site ' end, and last base of its 3 ' end is the previous base that is close to SNP just.Primer length is between 18～46base, and the Tm value is between 55～80 ℃.Preparation several sites on the same group are dissimilar alternately appearance, and its length differs 4 (or its multiple) bases, and can not form hairpin structure between them, and long SBE primer can not form secondary structures such as inflection.Reference literature (Lindhlad-Toh K, Winchester E, Daly MJ, et al.Lange-scale discoveryand genotyping of single-nucleotide polymorphisms in the mouse.Nat.Genet..2000,24:381-386).
In addition, design is as the dna fragmentation of the FAM mark of molecular weight size criteria, and its size is respectively: 19bp, 23bp, 27bp, 31bp, 35bp, 39bp, 43bp, 47bp, all sequences are AT and repeat to form.
1.2) PCR reaction and product evaluation: a plurality of SNP site (being generally 3-5) of dissimilar and different SBE primer lengths is combined as one group, carries out the respective number dna fragmentation that the multiplex PCR amplification comprises the SNP site earlier.Reaction system 5 μ l, each component is as follows:
Title original liquid concentration application of sample amount (μ l) system final concentration
Mg
2+??????25mM????????0.6???????????3mM
Damping fluid 10 * 0.5 1 *
dNTP???????2mM?????????0.075?????????30nM
Each 0.1 μ M of primer 10 μ M 0.05 * n
AmpliGold??5U/μl??????0.05??????????0.05U/μl
Template 50ng/ μ l 1 5ng/ μ l
DdH
2O polishing to 5 μ l
Adopt Touch-down PCR, its program is as follows: after 94 ℃, 12 minutes, carried out 94 ℃ 30 seconds, 63 ℃ of 15 round-robin 30 seconds (each circulating temperature descends 0.5 ℃), 72 ℃ 50 seconds, 94 ℃ 30 seconds, 56 ℃ 30 seconds, 72 ℃ of 24 round-robin are 50 seconds subsequently, last 72 ℃ 10 minutes twice.Reaction finishes the back to be identified with 1% agarose electrophoresis, observes to have or not product under the UV lamp, and takes pictures writing time, site title, sample number etc. at ultraviolet gel imaging instrument.
1.3) remaining dNTP and the strand primer that participates in reaction can influence next step SBE reaction in the system of PCR product purification: PCR reaction back, need remove the two so be used as the PCR product of SBE reaction template.(Shrimp AlkalinePhosphatase SAP) can remove the phosphate group of dNTP 5 ' end shrimp alkaline phosphotase, makes it to form phosphodiester bond, thereby can not participate in the extension of DNA chain; (Exonuclease I ExoI) can influence next step SBE reaction thereby avoid PCR to react remaining primer from 3 of single stranded DNA ' hold 5 ' extreme direction Nucleotide of degrading one by one to exonuclease I.
In per 5 μ l PCR products, add 2 μ l enzyme mixed solutions, wherein contain SAP 0.5U/ μ l, ExoI 1U/ μ l, mixing is inserted 37 ℃ of water baths digestion 1 hour, and it is centrifugal to take out the back, and 85 ℃ of 15min deactivation SAP and Exo I are as the SBE reaction template.
1.4) the LM-SBE reaction: owing to have only fluorescently-labeled ddNTP (to be respectively JOE-ddATP in this experiment in the system, FAM-ddGTP, TAMRA-ddCTP ROX-ddUTP), use is reacted than higher hot Sequenase (ThermoSequenase) fluorescent mark ddNTP incorporation efficiency, can make each SBE primer only extend a base in reaction and only promptly come to an end.Although amplification is a linear growth, after 40 circulations, under the situation of ddNTP capacity, its total amount has also reached 40 times of template, is enough to detect.
Reaction system is 5 μ l, and each component is as follows:
Title original liquid concentration application of sample amount (μ l) system final concentration
Mg
2+??????????????25mM??????0.5???????????2.5mM
Damping fluid 10 * 0.5 1 *
JOE-ddATP??????????0.12μM???0.1???????????2.4nM
FAM-ddGTP??????????0.12μM???0.1???????????2.4nM
TAMRA-ddCTP????????0.12μM???0.1???????????2.4nM
ROX-ddUTP??????????0.60μM???0.1???????????12nM
SBE primer 2 μ M 0.05 * n 40nM
Theromo?Sequenase??10U/μl???0.025?????????0.05U/μl
Template 1
DdH
2O polishing to 5 μ l
Response procedures is: after 95 ℃, 3 minutes, carried out 95 ℃ 30 seconds, 50 ℃ 30 seconds, 60 ℃ of 40 round-robin 40 seconds, last 60 ℃ 2 minutes.
1.5) electrophoresis: SBE product 1 μ l mixes with the sample-loading buffer equal proportion, carries out electrophoresis on 377 sequenators.30 minutes 2 times application of samples in the time of can be respectively at electrophoresis during application of sample and behind the application of sample respectively add the size criteria in a hole respectively at the two ends of well.Electrophoresis finishes the back by observing SBE product electrophoresis position and comparing with size criteria, can judge it is which site.
1.6) genotype judgement and data preparation: judge the SNP genotype according to the band color, blueness is G/G, and green is A/A, and yellow is C/C, red T/T, indigo plant/green is A/G, Huang/redness is C/T.With each site somatotype result arrangement is that the Excel form is to carry out statistical treatment.
2) SnaPshot
TMCarry out gene type:
SnaPshot
TMBe the test kit of PE company based on the gene type of the principle exploitation of single-basic extension (SBE), the extension of multi-primers specificity is used for a plurality of SNP site and does gene type simultaneously, must be at ABI
Move on 3700 sequenators.
2.1) need the SNP site of somatotype, generally same system is put in 7～8 sites, primer 3 ' terminal must design in the upstream in SNP site or the contiguous site in downstream, regularly react with common PCR.The Tm value of each primer is best approaching, can not be lower than 50 ℃;
2.2) before primer, add and make the polyT of suitable length to differ 4bp between each site at least, and make two contiguous sites not have the base that overlaps as far as possible, (for example 3 sites are C/T successively, A/G, C/T);
2.3) contain the dna fragmentation in each SNP site respectively with ordinary method PCR, demarcate balanced mix after the concentration, purifying;
2.4) with the extension primer balanced mix in each SNP site and be diluted to and be respectively 0.5 μ M.With the 1 μ l mixing of the PCR product mixtures behind SNaPshot reaction mixture 2 μ l, primer mixture 2 μ l and the purifying, 96 ℃ of 10s, 50 ℃ of 5s, 60 ℃ of 30s, 30 circulations are carried out primer specificity and are extended.Add 70% ethanol of 9 times of volumes in the reaction product, left standstill under the normal temperature 20 minutes, 4 ℃ 4000 left the heart 45 minutes, abandoned supernatant, added 70% ethanol of 9 times of volumes again, left standstill 20 minutes, and similarity condition is centrifugal, abandons supernatant, and 1300 commentaries on classics are inverted centrifugal.Dried in the air 30 minutes, and added 6 μ l distilled waters.
2.5) last sample of SNaPshot and interpretation: every hole adds methane amide (Hi-Di Formamide) 9 μ l, length mark 0.2 μ l, SNaPshot reaction product 3 μ l, 95 ℃ of sex change 5 minutes, capillary electrophoresis is being carried out in the cooling back on ABI PRISM 3700 dna sequencing instrument, operation Genescan 3.7 carries out data analysis, and Genotyper3.7 exports the genotype of everybody point of each sample;
3) RFLP-PCR carries out the SNP somatotype: for the SNP that changes restriction enzyme site, can advanced performing PCR amplification, amplified production digests with corresponding restriction endonuclease, behind the electrophoresis according to band location determination genotype.Complete degestion or can not be digested be two kinds different homozygous, not exclusively enzyme is cut is heterozygous.
4) sequencing and typing: carry out sequencing and typing with above two kinds of method somatotypes or the unfavorable site of somatotype result for being not suitable for.
More than the somatotype in each SNP site all in the normal control individuality of 96 picked at random, carry out earlier.
In case group and control group, the SNP site of above-mentioned 80 somatotypes all meets the Hardy-Weinberg balance.Analyze through SPSS statistical software 10.0 editions (free download is in http://linkage.rockefeller.edu/soft/), there is 1 SNP site to be positioned at the 16th of o.11 exon of sAC gene, numbering in the snp database of NCBI is (rs203849), gene frequency is distributed in that difference has statistical significance (P＜0.05) in two groups, and is as shown in table 7.
Table 7 case group and control group SNP somatotype SPSS statistic analysis result
Allelotrope
SNP C T A G amounts to the P value
Case group 147 297 444 0.005
Rs203849 control group 69 225 294
Amount to 216 522 738
There is significant difference in the gene frequency of 1 SNP site rs203849 that is arranged in the L10N2 segment of SAC gene in case group and control group, therefore points out this site relevant with diabetes B.And then prompting SAC gene is a kind of new diabetes tumor susceptibility gene.
The genome sequence of SAC is shown in SEQ ID NO:17, total length is 104,424bp, the SNP site (Y) of being disclosed is positioned at 33 of this gene, 527-34, between 327, this regional nucleotide sequence is shown in Figure 1A, and Y is the SNP site among the figure, and it represents base T/C polymorphism, promptly this site can be T, also can be C.This regional complementary sequence is shown in Figure 1B, and R represents the complementary base in described SNP site among the figure, and it represents base A/G.
Based on this SNP site, can design the primer of suitable length, be used for predicting diabetes susceptibility through pcr amplification.
The prediction of embodiment 3 prediction diabetes susceptibility primer design and diabetes susceptibility
1.SBE primer
Primer will be positioned at the 5 ' end in SNP site, and last base of its 3 ' end is the previous base that is close to SNP just.This primer has one.Length is between 18-46 the base.Avoid containing too much G+C, the Tm value is between 50～65 ℃.Because conversion hysteria is more in the SNP site, therefore should avoid the identical sequence type of continuous several appearance (as continuous several C/T types), as when running into several sites of preparing to put into same group and all being the C/T type, wherein several can be designed from anti-chain, promptly become the A/G type, preferably C/T and A/G occur at interval.Formation such as hair fastener can not be arranged between preparation several sites on the same group in addition, and long SBE primer can not form secondary structures such as inflection.A primer according to above principle design is: 5 ' CCG ATG GAT ACA GTT CTG GTG CAG G 3 ' (SEQ ID NO:25), perhaps 5 ' GTT GCC AGT GGG ATT GTC TTC TGT G 3 ' (SEQ ID NO:26) its be the same preface primer of this chain, promptly combine with its complementary strand.Genes of individuals group DNA to be measured is carried out the sequence in SBE reaction detection SNP site with this SBE primer.
2, regular-PCR amplimer
According to the sequence (Figure 1A and 1B) at place, SNP site, the primer of design shown in SEQ ID NO:1-24.As shown in table 1ly carry out various combinations.With the described primer that is combined as, be that template is carried out pcr amplification with the genomic dna that derives from individual blood sample to be measured, amplified production is checked order detect the single nucleotide polymorphism in described SNP site.
SEQUENCE?LISTING
＜110〉Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences
Sinogenomax Co., Ltd.
Nanfang Research Centre, State Human Gene Group
The Chinese Academy of Medical Sciences Beijing Union Medical College Hospital
＜120〉be used to predict the test kit and the primer of diabetes B susceptibility
<130>I20030512CB
<160>27
<170>PatentIn?version?3.1
<210>1
<211>20
<212>DNA
＜213〉artificial sequence
<400>1
ccaacgggta?gagaaaatcc???????????????????????????????????20
<210>2
<211>20
<212>DNA
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<400>2
tgctgtgttt?gcagaaagaa???????????????????????????????????20
<210>3
<211>20
<212>DNA
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<400>3
ttgcagaaag?aaagctggag???????????????????????????????????20
<210>4
<211>20
<212>DNA
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<400>4
cacaaatctt?gtctcccctg???????????????????????????????????20
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gggctcatgt?ctcactcatt????????????????????????????????????20
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<211>20
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<400>6
ggccatgtag?aaatgccata????????????????????????????????????20
<210>7
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<400>7
tcgtgtctca?cagtgtgtcc????????????????????????????????????20
<210>8
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<212>DNA
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<400>8
aaaatccttt?cccacccttt????????????????????????????????????20
<210>9
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<212>DNA
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<400>9
tttgcagaaa?gaaagctgga????????????????????????????????????20
<210>10
<211>20
<212>DNA
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<400>10
tgaggcataa?gtagggaggg????????????????????????????????????20
<210>11
<211>20
<212>DNA
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<400>11
ggatacagtt?ctggtgcagg????????????????????????????????????20
<210>12
<211>20
<212>DNA
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<400>12
gcagggaaca?ggaaagaaag????????????????????????????????20
<210>13
<211>20
<212>DNA
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<400>13
ctcatttttg?tgcttcctcc????????????????????????????????20
<210>14
<211>20
<212>DNA
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<400>14
agggctcatg?tctcactcat????????????????????????????????20
<210>15
<211>21
<212>DNA
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<400>15
tttgaggcat?aagtagggagg???????????????????????????????21
<210>16
<211>19
<212>DNA
＜213〉artificial sequence
<400>16
aggcataagt?agggagggc??????????????????????????????????19
<210>17
<211>19
<212>DNA
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<400>17
atgcacactc?tgcaagcat??????????????????????????????????19
<210>18
<211>20
<212>DNA
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<400>18
acactctgca?agcattgagg??????????????????????????????????20
<210>19
<211>19
<212>DNA
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<400>19
cactctgcaa?gcattgagg???????????????????????????????????19
<210>20
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<212>DNA
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gttgctgtct?ctctccctca??????????????????????????????????20
<210>21
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agctgtggtt?gctgtctctc??????????????????????????????????20
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<211>20
<212>DNA
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ctgacccttt?tgaggcataa??????????????????????????????????20
<210>23
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<212>DNA
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atatagcctc?ccactgctcc??????????????????????????????????20
<210>24
<211>20
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taaagtttct?gagggcaggg??????????????????????????????????????20
<210>25
<211>25
<212>DNA
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ccgatggata?cagttctggt?gcagg????????????????????????????????25
<210>26
<211>25
<212>DNA
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<400>26
gttgccagtg?ggattgtctt?ctgtg????????????????????????????????25
<210>27
<211>104424
<212>DNA
<213>Homo?sapiens
<400>27
gacagacatg?gcgcttcagc?tgtcttcaga?ataatgtcac?ccggcctcct?ctcctgtctt?????60
ctgcagtctt?aaaagaccta?gtccctaact?gaggtctggc?ttttcctcag?ccctggatga????120
agtggaggta?tgtggaagta?agagtctcag?cagaaagatt?gattgcagag?ctgaagatga????180
gggcgaccgt?caggaaagaa?gacagctatt?gcagaggagt?gggaagcctg?gggctagaag????240
tcagggttca?agtttgtgta?tacctctgtg?tcagtccctt?acatgagctt?agaagcttga????300
aggcttaaat?attgcctcac?cttctcaacc?tggatgctct?gtctttctag?cttactttct????360
ttatttgcct?cttttctgca?gtttctcacg?tgatatcctc?ctttttatca?gtcaacaact????420
accaagtgcc?tacctcttga?agggggctct?ggcaaggtgc?tgtggagtaa?acaaagatat????480
gtagaagatg?gttccaaacg?gggagcttac?aattcagatg?aagacaaaat?agaagcaatt????540
caaaagataa?tcaaggatat?ttgtatggga?aataagccac?ttaagtgtag?acattaagag????600
ccacaatagc?tcagaagaaa?aattaccatg?gctagagtag?gcaagcaagc?tttcatgaca????660
ggtaacactg?tgcctttaag?ttcagagtat?ctccctcttt?ggactcgtga?aacctgactt????720
tacatgtagg?tgaaaagttg?aatataaaat?ctattaggaa?attctagagg?agagatttag????780
agaaactgat?gaatataatc?gaaccctaat?ttctcttttc?atttttgggt?actactgagt?????840
tttctttact?cacactccgc?attcaggaat?ccttcttggt?ttatctttcg?ggcctcattc?????900
gcctgcttgc?cttttgactc?aggtatcctc?atttctcatt?ccaaggtgct?tccgcgcttt?????960
gtcagtaccc?atgctgttca?tgctgtattc?ttgatgtgat?agaattggct?gaacagttga????1020
taagggtacc?atcaacatgc?attgaaagtg?ctcttaaatt?aaacctacat?cttttgtcta????1080
ggtcatatac?atccccaaag?tgctataaag?cgtatacaaa?tgggatatag?catgatatag????1140
tagaaacaac?agggactttc?aagtcccaca?gacctggata?ttccagcttt?ataacccaga????1200
gcaagttaat?acctctgtgc?ttcagttttc?atatctatag?aaatcaggtc?tacttcatag????1260
cgctgtttgg?atgattaaat?gaggcaacct?atgtagaatt?gatacggctc?cgatgagtgg????1320
aggaacacca?aggttcttag?tcctcatccc?ggtttagata?aaacgacaca?gacacatgtg????1380
gagtgatttt?aaggatcgga?gagtttaata?ggcaagaagg?aagaggaaag?agggaagaag????1440
ctcccccata?cagagacaga?gggagggggg?ctccaaagcc?gagagaggga?acccccagtg????1500
gggtggacgt?cagctaggta?tatattacag?acgctggagg?aggcagtgtc?tgatttgcat????1560
agggttcagg?ggattggttt?gaccaggcat?gtcattcaca?aagcccttga?aaaagctagc????1620
cctctcaccc?tagcctttta?atatgcaaat?gcagggtgcc?atgatgttct?acacacgtgg????1680
gagtatgtgg?aggtggccat?gttgccagga?acatgtgggg?caagggaaag?aaggcctccg????1740
gaatcgccat?gttgggtggg?ccctgtttct?aatggccttc?atttgcttat?caaaggttgc????1800
cggcctggct?ctaagagcca?aggctttaca?agaaattttc?tggagatgct?ttaaaaaatg????1860
aaaatttccc?aaggacccct?tttcctctct?atctgcctaa?aataatttct?taataactcc????1920
tacaatagaa?tgcttcacat?aaaaaggtca?taataaatta?taattacaat?gtggtatgtg????1980
cctgtagaaa?ggtaaataca?gctatcacta?atcattttgt?gatgttgcag?aacttaaagc????2040
agaaaactat?atcttcaaaa?atagaaaatt?tctattgtct?tttatgggtg?ttcataagaa????2100
actcccagat?atttatttta?gatctccctg?ccttttaaac?ctatcatttt?cttcttttag????2160
tttcacatct?acatatgcca?tcttaatctc?aaaatgcatg?tactttcctt?gtttggtcat????2220
cataaacaga?aaaatctgtc?caagttcatt?cacatcacct?taattaaaac?aatagaatct????2280
taacaatcat?ctaattcatc?tctacactga?ctaaaatcac?ctctgtttga?aacgcttgtt????2340
ctccaatgcc?ataaagaaat?agcacttgaa?cataaattta?tttagtaagg?gcatttttac????2400
ttcctgcaga?gagggtatac?tcgccagcag?ttttgccacg?agagtacact?gaacaaagga????2460
gacggggtca?tttataacct?gacacgttca?ccctactgcc?cattggccgg?aacaggacct????2520
cacattctgt?atttgtcccg?atcggctagc?aacttagaac?ttttaaaaga?ggcaaaggta????2580
gaggagaaca?aaagaaggag?gaagtaactt?gtggaatgct?gagaaaagta?aaaatacttt????2640
taaataagga?agaggaacag?gctatgacct?aatggttgct?tggaccagta?taagcatgcc????2700
agggcaaata?tttaggctac?attgtgggag?ccaagaacat?aaagtacatt?gatttcttta????2760
ttatggctag?cagatattta?agaatgttag?cacaggtctt?tgaataaatt?ttgcttttaa????2820
gataagttac?tatttattcc?taattagacg?gggaggaaag?tctttgaaga?ggaacctcta????2880
ctttactttt?tatacctcta?ccctcacagg?tagatagcta?ttcaacactt?cctaaaactg????2940
cccagtttga?acactcattc?ttacattgtt?tatatttgtc?cttcggtgat?tgccagtcat????3000
tgatcctagt?tgatcctgag?caacaaagaa?taaacctaac?ccactttcca?tccagtgtta????3060
acaactttag?caaaacagtc?tatactatgc?atgtgaggag?agtgtggtat?tgccaagatt????3120
gaaggggctg?atagtagggc?tgctagaaag?aatgcaatgt?ttggaatata?tttatactaa????3180
aaaattgttt?atttaaaatt?cagatttaac?tgagcatcct?ctgttttcat?tagctcagtc????3240
tttcaatctt?acaagcttgg?tagctaaaga?agtcaaagtt?gagccagtga?actgggggca????3300
ggagagggaa?gaatagagct?acgccctgct?cagttctgct?cagtcctatc?ttagttctct????3360
ggctactcag?cacatctgtg?gaagccactt?cagagcaccc?atgcctacgg?aacatactgt????3420
ttacagtcac?ttattctttg?ataactagct?ccctccactg?aagaaaaaca?caccaacttt????3480
cctttcccac?tgcatacttc?ccatgaactt?taatcttgct?aacccaaacc?aaatttctac????3540
ctcaaggaga?aggtagggaa?gttgttcttt?gattgcaggg?tcccacatta?caccttgcat????3600
acacacccat?gtcccccact?tagcccacgt?ccaccactta?ccccacaact?ttcacagttc????3660
agcccaaata?tttgaagaca?actacaattt?taaccaaaat?gtcataattt?tctgacttat????3720
ttccagtctc?tgccatcatt?cctcacattc?cagagtcaat?gaattttaaa?gaggtcaatg????3780
aacttcagtc?ctctggatta?gatttgaaca?cttttatgta?tcttaaaatt?gcattgcatc????3840
caaatagcta?gttaacatat?gaaaaggtgc?ttaatctcct?tagtaccaac?aaggaaacac????3900
aaaaccacag?ataccattgt?agcaggacga?gccacagaca?aaacccctta?gacacccggg????3960
ttaaagaagg?aagaggcttt?attcggctgg?gagcattggc?agacttgcat?ctcaagaact????4020
gaggtcccca?aagaaacagt?tcctggccct?tttaagggct?tagagctgtg?aggggttcca????4080
cgtgaaaggg?tcataataga?ttgagatctg?tagatagcac?atgtggttag?aatgggggtt????4140
aatcttttaa?cctcagacct?ggtcatcagt?ggcgccggct?ggtcttgcca?ctgacttcat???4200
tcctgtgttt?ttcagctttt?acttcctctt?tctcttcaga?gacaagagac?agtaagagaa???4260
atggcctgtc?tcctcaccac?cacttaccta?gcaagatgac?taaaagttga?aaagcctgac???4320
aaaataagtg?ttggctgaga?tatgtagcaa?ctgaactgtc?ataccttgcc?tgagggagtg???4380
taagttggta?ccatcacttt?ggaaagctgt?ttagcaagat?ctactcaagc?aggggtatcc???4440
aatctttcgg?cttccctggg?gcacaattgg?aagaggaaga?atcatcttgg?gccacacata???4500
aaataatact?aacaataatg?atagctgatg?agctaagaaa?aaaaaatcac?aaaaaaatct???4560
cataatgttt?taagaaagtt?tacaaatttg?tgttgggctg?cattcaaagc?catcctggac???4620
cgcatgtggc?ccacaggaca?tagcttggac?aagcctgtac?taaagtttaa?catgtgtata???4680
ccctatgacc?cagcaattcc?actcctgtgt?atatacccag?gagaaatgca?tacatctttt???4740
caccaaaaca?catgaataag?aatgttctta?gcaccattat?tcataatggt?ctaaaagtgg???4800
gaacaaccca?caggtcaata?gtatagtgga?taaatgtttt?gtggtatatt?ccatcaggtg???4860
atggaatact?atatagcatt?gaaaatgaac?aattattgat?atacaacaac?atggatgaat???4920
atcacaaaca?caaaatatgt?agtatgattt?catttatata?aagtttgaaa?actggcaaag???4980
gtgatctatg?ttgttagaaa?taagaaaggt?taccttcagg?gaaaagagaa?gggtagtgac???5040
ttgaaggtgg?catgagaaaa?acttctggaa?agctggtaat?gttttccttc?ttgctatgaa???5100
tgggtattac?acggatttgc?tcaccttaga?gtaattcaag?ctatacactt?atgatttgta???5160
cattttccta?catgtatgtt?atgcttcaat?aaaagttttt?taaaagatag?cactaatttg???5220
cagtaaatct?agttttttag?cacctcgtgc?ttatgcattt?gattttgtta?aaaactctaa???5280
acacagcact?ttgcacttat?tcttttgaaa?tttcattatt?ttggttgatt?aagatgtatt???5340
aaaatcctag?ctctgtcatc?agtgcattag?ttctctcact?atattttcaa?attttatttt???5400
ccctcagctt?tattaaggca?aaaatgacaa?aaagtgtaca?tatttatggt?gtacaatgtg???5460
atgttttaat?atatgtatac?attatgaaat?aattaaatca?aggtaattaa?cgtatcatct???5520
cacatactta?acatttttgt?gtggtgagaa?cagttaagat?ctactctctt?agccattttg???5580
aagtatataa?tactttatta?actgtattca?ccttgctcta?ggttagatct?ccaggacttt???5640
ttcattgggt?ctaattgaaa?ctttgtatcc?ttcagccacc?aacatctcat?tccacccacc???5700
caaccccagc?ctcaggcatc?accattctac?tctgcttcta?tgattttgac?ttttttagat???5760
tccatatata?agtgagatcg?ttcaatattt?ttgtctttct?gtggccggct?tatttcactt???5820
aacataaggc?cctccaggtt?catccacact?atcatacaag?aaagaatttc?cttctgtttt????5880
acggctgaat?agtactccat?tgtatacatt?atccaatgtt?ttctttatcc?attcatatgt????5940
tgatgaacaa?ttaggttggt?tccatatctt?ggctattgtg?aatagtgctg?aaataaacat????6000
gggagtgcag?ggatactgat?ttcaattcct?ttgggtatat?acccagatgt?gggattgtta????6060
gatcatatgg?tagttctatt?tttaattttt?taggaacctg?catattattt?tccataatgg????6120
ccgtactttc?aattatatct?ttatcaaagt?cttctatcgt?gcccatggag?gcttacctct????6180
gagttgacac?cagaatacta?atcaatttcc?attaggtgtg?attgctaacc?agccaattat????6240
attttcttta?ttcctataat?tttgtatatt?ttactcacaa?ggatatgaga?aatttggcca????6300
aatgccttaa?agtcaatata?tacattgtct?atagcagtct?cttgatttaa?aagtttaata????6360
actcttccaa?aataggaaat?aatgttggct?tgctcttggc?tctgaatcca?tttgactcct????6420
tttaatcacc?tcttgctaat?ctaaataacc?attgaggctg?ctcccaaata?ttccaactct????6480
ctttcctatt?gtgcacatgg?taggagtgca?cttccctgtc?tacttgaaac?taggcatggt????6540
catgtaattt?gctttggtca?atgccatgag?taaaagtgaa?atacgtcact?tctgggagta????6600
gaatgagtat?actccactac?atcctctttc?ccactacctt?gacaaccaga?atattccagt????6660
ttgggtccca?aagtgaaggc?aaaaacagag?gagaacccca?tacaacccac?aagggacatg????6720
tagtgtgagc?aagaaatgaa?caagaaataa?gcctttgtta?tttcaagcca?ttgagatttc????6780
aaagttattt?gataatgaaa?cataacctgt?attatctcaa?caaatacatt?atgtttactg????6840
gtctgtgttt?tctgggatcc?atgagtagcc?tcatcttttg?aaattcaaaa?gagaatgtgc????6900
ccatctatgg?tattccagcc?catctcttgt?tctccatggt?tttttgagat?tactgacatt????6960
acacctgtca?gttctttcag?tatctgtaga?tatatgttgt?ctgggactag?ctagaattta????7020
tttaaaatga?ctgtgtgctt?tagcactact?tatcttggat?ttcaattctt?tcttagcaat????7080
gcttgttata?cttttcaatc?ctccatggtg?gagaaggtag?aaacaaaaga?aaaggtgtat????7140
ggtacaccat?acttaagctt?catccttatt?cctcttttat?taattacctt?gttttcaaca????7200
aagcctttaa?aaatccctct?aggttttctt?aactttagca?ttttttgtaa?gtctttcatt????7260
ctcgacattc?aattttcttg?tacctttctt?tttattatca?ttattattat?tttagagatg????7320
gagtctcact?ctgtcaccta?ggatagagtg?cagtgacacg?atctcagctc?cttgcagcct????7380
tgacctcctg?ggctcaagcc?atcctcccac?ctcagcctcc?tgaatagctg?ggactacagg????7440
tgcatgccac?cacacccagc?aatttttttt?tttttttttt?gtagagatgg?gatttcacta????7500
tgttgcccaa?gctggtctcg?aactcgggct?caagcaatac?tcctgtgtag?gcctcccaaa????7560
gtgctgggat?tataggcaca?aaccactgca?tctagcatct?cacacccttc?ttaaaagttc????7620
atatagcacc?aaatttacta?tctgaagtta?tttatttgat?ttaattttat?ctattgactg????7680
ttcctggcac?atgctgtggt?cttttgctgc?atttttaatg?ctaccctttt?tttttttaaa????7740
ccttagttat?atgtttcttt?cttttgttca?cttcttaaca?tttgagtttg?ccaggacttt????7800
tccttttaaa?ggttatccaa?tatgtaacat?ttagcactca?ttttttagaa?tactaaatac????7860
atttttaaat?gtatactata?tacattttaa?agtttgtctg?ttaaatgtac?aaatattttt????7920
ccctgagtta?ttttttaaat?acttcccctt?aaatctaagg?gatataagcg?actgtctcaa????7980
ttttttcctc?taatactcta?atatatccca?atatgaccta?ctaacaagtt?cctctctgct????8040
ggtcagaatt?aaaccaaaaa?taacagttcc?ttttcttaaa?aaaacaaatc?ctcttatatt????8100
ttctgtataa?cctattccag?taacttggat?tgctctgaaa?aagtaaaggg?tgtttgcttt????8160
tactgttcag?gctggtagag?catgattttt?acaacattta?ggcatgagca?tttaatctgc????8220
cccagcagct?acaggaaggc?cttaggaaat?cctagttttc?tcagaactaa?ctgggcaaca????8280
aattgaaatt?tcagcatttc?cttccattta?cagcttaagg?tcttccatct?ttccagctgc????8340
cacacacaca?cacacacaca?cacatttctg?aactcttttc?ttccatttat?ttaacattat????8400
acctttatag?tcttaatctc?ttgcctatat?acaaaactct?aatactcact?tacatataaa????8460
tacactcaca?cacacgaatc?acatctacac?tttttttttt?tttaaagaga?gaaaaaagta????8520
aaagaccaag?gtagagagag?ggtaaaagga?aacatgagga?cagaagaaaa?agaagtctgg????8580
cctgagtgaa?tagagcttaa?cagcccacta?caactggact?tgccctgcga?gggcctaccc????8640
cttcctgcaa?atgagttgag?ccgttcagct?accctctttc?accccagcct?ctttgtaatg????8700
gagctcactt?atgcaacagc?tgttcagggt?gggagggttc?ttcctctgta?tagaaattgg????8760
cccttttgaa?gtgtggctca?acaactctgg?cattttcacc?actataagca?ggccgcaggt????8820
tagaacaaaa?caaatggaga?aagagcaata?ggaaaatgag?caaatgaata?tatcagattt????8880
cctctatttc?aattttcttt?ttagaagacc?tatttggaga?ctgcttcctg?tcaccataaa????8940
atcctgaaca?tttgtcttga?acatgaacac?tccaaaagaa?gaattccagg?actggcccat????9000
agtcagaata?gcagctcatt?taccagacct?cattgtctat?ggacatttct?ccccagagcg????9060
accctttatg?gattattttg?acggagtcct?gatgtttgtt?gatatttcag?gcaagtgcaa????9120
aagggatgtt?tgtttaatgt?ggatgagcaa?caggctcgcg?tgggaattca?catgcagagc????9180
ttgattgcag?agtagggagg?ccattctgga?gcccttgggc?tgtcacagca?gatgtgctcc?????9240
actgagaaca?caagagggag?gaaatagctt?gtggccctgg?ctctctctca?tcctccctta?????9300
ctcaggactg?ccagtcatag?gcatatcttt?aacatgctca?agtcccattc?tttgctccag?????9360
tatctctgcc?ccaacttcac?tgactcatcc?tctccagccc?caagccccat?acacatccca?????9420
gtcaaaattg?acctcaggaa?atgatctccc?tagatgatgt?ttacatctta?ctaataaact?????9480
tgccacctct?tcagaagtgt?ttgaaatgtg?tgtgtttttg?ttaccacgga?atgaaaattt?????9540
tattcccagt?taaagaagtt?gcagttatca?ctgtacagtt?gagaatttgg?aagaaagaaa?????9600
tatctggagc?cttttcctga?cccctaaaat?aatagctaga?ggaggctgca?tgtctgacac?????9660
ttgaccagcc?acaaagatcc?ttaagaagaa?actctgcctg?tttttaaaag?ctgaggccac?????9720
cgggttcggt?ggctcacgcc?tgcaatccca?acacttttgg?aggccgagga?gggcggatca?????9780
caaggtcagg?agttcgagac?catcctggct?aacatggtga?aaccccatct?gtactaaaaa?????9840
tacaaaaacg?agcctggcat?ggtggcgcac?gcttatagtc?ccagctgctc?ggaaggctga?????9900
ggcaggagaa?ttgcttgaac?ccgggaggcg?gaggttgcag?tgagctgaga?tcacaccatt?????9960
gccctccagc?ctgggctaca?aagcaagact?ctgtctcaaa?aaaaaaaaaa?aaaaaaaaaa????10020
gctgaggccc?gctgccttcc?agggtagtcc?tcttctggct?ctgtttgatt?cccccaagca????10080
gccaaggaaa?ccagctgcac?atttattcca?ggttttactg?caatgactga?gaagttcagc????10140
agtgccatgt?acatggacag?aggggctgag?cagttggtgg?agatcctcaa?ctaccacata????10200
agtgcaatag?tggagagtaa?gtgttcccat?aggtttctgg?cttgagaata?tttcaattca????10260
ttgttttttc?cgtagttgtc?aattataacc?tgatagagta?caattgctta?gcactcctcc????10320
tcttccccat?gaaatgtgta?taaaaccagt?cttttttgaa?atatgatata?gtataactga????10380
agaaataaat?ataatcaaac?ctcactaata?cagactattt?gagggaaggg?atgttttgtg????10440
ttagagggct?gaattataca?ctgcttttaa?aagaactgta?gtagtaatac?ttttagttat????10500
atatccaagt?atttatattt?atttttattt?atttatttag?agacagagtc?ttgctctgtc????10560
gcccaggctg?gagtgcagtg?gcacaatctt?ggctcactgc?aaccttcgcc?tcctgggttc????10620
aagcaattct?catgtctcag?cctcccgagt?agctaggatt?acaggcgccc?gcccccacac????10680
ctgtctaatt?gttgtatttt?tagtagagat?ggggtctcac?catgttggcc?aggctggtct????10740
caaactcctg?acctcaagtg?atccacctgc?ctcagccccc?caaagtgctg?ggattacagg????10800
tgagagccag?ggtgcccggc?tatttttatt?tattaatttt?tttttttgag?tcagagtctc????10860
actctgtctc?ccaggctgga?gtgcagtggc?acgatctcag?ctcactgcag?cctctgcctc??10920
ccaggttcaa?gcgattctcc?tgcctcagcc?acacacgtag?ctggggttac?aggcgtgcgc??10980
caccatgccc?agcaattttg?tatttttttc?agtagagata?gggttttacc?atgttggcca??11040
ggctggtctc?taactcctga?cctcaggtga?tcctcccacc?tcagcctccc?aaagtgctgg??11100
gattataggc?gtaagccacc?atgcctggcc?tatccaagta?tttttaaaag?ccagcatcta??11160
taaaacccaa?agatagtcat?taagagattg?ttgtatgagt?agataaatga?tttataatta??11220
gcttctcaat?aatttgtctc?ctaatgatgg?atgctgaagc?acttagagtg?aactgaaaac??11280
tttagtcccc?ttgtcaacct?ctgcctgcca?tcttgtttgc?attgttaatt?caaactattc??11340
atgaagacaa?cggtttactc?tgttatggtg?aactcctggc?ctagtgtttt?atcagactct??11400
gagttcctta?gtaatatctt?gatgttaccc?actagacaaa?atttaatgct?tcataaaagc??11460
aggaactatg?gttgattcct?ttctgcatct?gacttggcac?aacaggtgct?taaccaatcc??11520
atgatgatgc?gtaactaaaa?gagagaatgg?ccatttatgc?cataccgtct?aaataaacaa??11580
aatacaaagt?tggtaataac?caaaaatgca?agtgactatg?gttgtgattt?tcccattccc??11640
tgactcctag?tttttgtgga?gtcctgtcat?tcatccaccc?acccatgctt?acacaagccc??11700
cagcctataa?catatattga?tcaataaatt?aattaaaagc?attccattat?cgtgggagga??11760
gggcagctgt?cttcatacct?catcagaaac?cctagctgcc?tttctcctgt?ctttccccat??11820
tcacagaaat?ggagcataga?tgtaaactgg?ttccacgtac?tcattctcca?cttgaggaaa??11880
cagactcaaa?tgggttaagt?ggcttgtctg?ggatgagatc?tttagtataa?gcctattctc??11940
tgaatcactg?ttcttttgac?ctagtttcta?ttccactaag?aaagaatgat?gtttttttac??12000
tacctttaag?gaatcagggt?ttgatttaat?tttttttttt?tttctcagaa?gtgttgattt??12060
ttggaggaga?catcctgaaa?tttgcaggta?tgggggctta?ctaagataga?aggggtaaga??12120
aaggagtgct?gaggtgcctg?tgcttctgtg?ttggggacaa?aggaggcatc?ctagagaagg??12180
gagtggccag?gagataggct?gaggaatgct?tgatgagtaa?gtttctatac?agatctcata??12240
caaaatagat?tgatccccag?ggcaggtcaa?aagcccgcgg?catgtctctc?tctgaaggtg??12300
atgcactgct?agccctgtgg?agggtggagc?gaaagcagct?gaaaaacatt?atcacagtgg??12360
taattaaatg?tagcctggag?atccatggat?tgtttgagac?ccaggagtgg?gaagaaggcc??12420
tagacatccg?agtcaagata?ggtaagcatt?tgagaaggaa?taaatcctac?ggcagctggg??12480
atagggtctt?gactcctggg?gcatctctct?ctcccaaaga?gaagtagtag?aacatggtgg??12540
ctcagcccca?tgatgccctg?aactttggca?tcaggacaat?cagaatgtga?attttggctt??12600
cctcacatac?cagttgagag?aatttgggtt?aatcataata?tctacctaat?aagctattac??12660
aaaaagtaaa?ttagttggta?tggtagttaa?tgcataggaa?ccacccaata?aaatagtctt??12720
tatgactgct?actgctgtta?ttattattcc?atcttgctgc?ttgtcaaggt?tgtgcagtat??12780
aaaacaaaat?agagactagc?ttgccattac?atagtttcag?caacgacatg?agactggtca??12840
ccccctacct?cataagaatg?aggtgtagga?aaagcttaac?aggtcagcct?gcaacacagc??12900
tccagcttta?cacaaggctt?cttaaagtta?tacatataat?atagtaatag?tcacacatat??12960
ttccttatta?cattgcagac?attacacact?atgcacgtgc?aaacattacg?cacactatat??13020
gacagtcctg?agatacaggc?atcattgtat?ccatttcata?gatgaaaaat?gagattctga??13080
gaggtataag?taatgagtaa?cagagttatg?gttggtgctg?ttggtgttag?cttccgccta??13140
actaaacttt?gcaaaactta?gaattctcac?atgtcatacc?tgataggatc?atcagcagtt??13200
atacaattaa?ctgtttctca?gccttcttta?acctaggccc?gcttttgatg?ttgttaaaaa??13260
tttccaaata?aggccaggtg?cagtggctca?cacctgtaat?cccagcactt?tgggaggcca??13320
aggtgggtgg?atcacctgag?gtcaggagtt?tgagaccagc?ctgaccaaca?tggtgaaacc??13380
ccgtctctac?taaaatacaa?aaattagcca?ggcgtgatgg?cgggtgcctg?taatctcagc??13440
tacttgggag?gctgaggcag?gagaattgct?tgaacccagg?aggcggaggt?tgcagtgagc??13500
cgagatggcg?ccattgcact?ccagcctggg?caacaagcgt?gaaactccat?ctcaaaaaaa??13560
aaagcccaaa?taagttaaat?attttgttga?aaaaaaaatc?aaagttatta?taatactgaa??13620
tattttttct?aagttagtac?ccaaggagtc?tgatgtgtta?tccttcttga?gaatgatggg??13680
aacccagccc?cctcttgcat?gctgattggc?tgttagtgag?gtgggtccca?gcaccttttt??13740
ttagagtaag?tccaaacatc?agtgtgtttc?agatagaaaa?caaactgtat?gtagaatcag??13800
gggggagtca?gccctgacaa?atcagtatag?cagagagcga?agataaaaaa?taaacattga??13860
ttgtattaca?gtcatttgaa?agaaatgtgt?gtcacttaca?gttcatttat?acatatattt??13920
tgtgtacatg?tcatattata?caatatcttc?ttctgtcact?taggttccaa?aactttcatt??13980
taccaactta?aaagcaatga?gagaaatggt?tgttgggatg?ggatgtgtaa?ctgtcaaatg??14040
catacttcct?ttcccccacc?ctttgttgtc?taaaattcaa?ccctaaggga?ttatttttag??14100
ttacagcttc?aatctctgct?aaaatgcaaa?ttctcccaaa?ataagaatta?ttaaaggtat??14160
tccctgttgc?ccttaagtat?acataattga?agaaaaggta?aaaataactt?tggggactgg??14220
taggaccatg?tagtgagata?atgttacaga?caggcaaaat?ttagtggtag?aactttctag??14280
ctttggaaga?aggggagctt?tggaaggccc?gagcccaaaa?gaggtatgcc?ataattccta??14340
tgtaaagttt?tagaagtgag?attttgctct?gagatagtat?agtcccacca?agattatggt??14400
ttttccaaaa?acctgtgctg?ctgggaaata?atccagaact?tcttgtgcaa?acctattcct??14460
tgccttcttg?ccaggactgg?ctgctggcca?catcagcatg?ttggtctttg?gagatgaaac??14520
acacagccac?tttctggtga?ttggtcaggc?agtggacgat?gtgcgccttg?cccagaacat??14580
ggctcagatg?aatgatgtta?ttctgtcacc?aaactgctgg?cagctctgtg?accggagcat??14640
gattgaaatt?gagagtgttc?cagatcagag?agcagttaag?gtgggtgtga?tgctgctact??14700
tacagaaagt?tctgccagcc?tgtaacagag?gccccctgcc?agaagagtca?ctgggcacgc??14760
tggtttcata?aagctcctgg?gctggagatt?gggatggggt?cagtctgggt?taggctacag??14820
aggctttagt?ccagggcagc?tcctctggga?ggagcccagg?ctggtgagct?tgaggaggaa??14880
atgattaggc?ttctttatgg?gtaactgagg?atatggaatt?tggggattga?ggccttttga??14940
ggggctagcg?accttgctta?aggaaccaga?agggtctgcc?ggttcatcca?ggagcagagg??15000
ggaatagttt?taaaggctgt?cattgaccct?cactttcttt?acccaacacc?ctcctaaccc??15060
aggatgaggg?atcactgaag?gtaaaggttg?gagttgagca?agtgcggcga?agttcagtga??15120
tagaagagag?acttctcttc?ctgtggctct?gcctagtaga?aaacattgtg?gttaagttgc??15180
agattgacta?taagcagaac?tgtccctggg?atatggacaa?ttaaaaaagc?tgtgctttga??15240
gggtatgaaa?gtggaagaaa?ggtgtgctgc?tagatgagcc?aaaggaatgg?gactacgcgg??15300
cagaaagaaa?gaaaagacag?agaatccgtg?cagatgctgg?tcaagatagg?aggcactccc??15360
acactcatgc?atcagcctac?aaccctcacc?accaccaccc?actcctcact?cttccagcaa??15420
gacatatcca?gcctgcatgg?cctagctggc?ttatagcaat?agcccattcc?catgctcttc??15480
aatcattctt?tttttaaaaa?aaaaaaaacg?gagtctcgct?ctgttgacca?ggctagagtg??15540
caatggcgtg?atctcggctc?actgcaacct?ccgcctcccg?ggttcaagca?attccctgcc??15600
tcaaccttcc?gagtcgctgg?aattacaggt?gcccgctacc?acgcccagct?aattttttgt??15660
atttttagta?gagacggggt?ttcaccatct?tggccaggct?ggtcttgaac?tcctgacttc??15720
gtgatccacc?cacctcagcc?tcccaaagtg?ctgggattat?aggtgtaagc?caccacgccc??15780
agcctctctt?caatcattct?tgataccttt?aaaaattgtt?ttaactttga?attcatgtta??15840
gacttacaga?aaagttgaaa?aaataataca?gagtttccat?atatccctca?cctaccttcc??15900
cctaatgtta?acatctttca?taacaagact?gcaatagtca?aaaccaggaa?attaacattg??15960
gtacaatact?atgcactagt?taaagacctt?atttgaatgt?caccagtttt?cccactgtgg??16020
tccacttagt?ggaatgttcc?aggactgtat?gcatgatctc?acattgcatt?ttgttgattt??16080
tttttttttt?tttttttttt?tttttgagac?agagtctctc?tctgtcgccc?caggcttgga??16140
gtgcagtggc?gcgatctcgg?ctcactgcaa?gctccgcctc?ccgggtttac?gccattcccc??16200
tgcctcagcc?tcccaagtag?ctgggactac?aggcgcccgc?cagtacgccc?ggctaatttt??16260
ttgtattttt?agtagagacg?gggtttcacc?gttttagccg?ggatggtctc?gatctcctgt??16320
cctcctgatc?cgcccgcctc?ggcctcccaa?agtgctggga?ttacaggcgt?gagcccctgg??16380
cgcccggcct?tgttgatatt?tttgatgtag?tctcctgcag?tctgcaacag?cacttcagtg??16440
gttccgttgt?cttgcagtga?ccgtgacaca?agagagttgc?cagccgatgt?tgtcacacac??16500
atctctggtt?agcactgcct?gatgctttct?ctcatctctt?ctgcatctcc?aacaacatat??16560
ctctctctct?ctctatatat?atatacatat?atatatattt?ttttttgaga?tggaatctta??16620
ctctgtcacc?cagtggggag?tgaggtggca?tgatctcagc?tcacttcaac?ctctaactcc??16680
cagtctcaag?cgattctccc?accacagcct?cctgagtaac?tgggaccaca?gacatgtgcc??16740
actacacctg?gctaattttt?tttttttttt?gtatttttgg?tagagacagg?atttcaccat??16800
tgttacccag?gctggtctcg?aactcctgag?ctcaagcaat?ctgcccacct?cagcctccca??16860
aagtgctagg?attacaggcc?tgatgttttc?tctttattgg?accaagttta?tgcttttttt??16920
tttttttaac?caagaatacc?acaaaaatga?gatcgtgcca?tcctcagtgt?gtcatcacat??16980
gtgtctcatg?atcttgatgt?cttatgactg?gtgatgctcc?taattccttt?ttggccatca??17040
gcccccgtcc?tttaacactt?ataaggaaga?aatggtgtgc?agtttaacca?ggttttattt??17100
gaattaaaat?gttatgaagg?aaaaaaagca?ggaaaaagtt?ctaagggcag?aaaagtataa??17160
gattagtccc?ccttggaatg?accctctctg?tacatatacc?aaacattgag?atgtgagtga??17220
acactgtaat?tggaaagatt?ttttagattt?tcaatttaaa?atttcaattt?tacaaatcaa??17280
atagtcttgg?tgtttaagtg?tgccaatcac?tgttcagtca?aaagcatact?ctctttctgc??17340
taagaaatta?cacttcaaag?gattaaacag?ttctcagaat?aactgaaaac?ttctcatttg??17400
cttttattta?ggttaacttc?ttaaaaccac?cccccaattt?taattttgat?gaatttttca??17460
caaagtgtac?gaccttcatg?cattattatc?cttctggtga?gcacaaaagt?aagtacccac??17520
catggaaaaa?tgcctttgcc?tctaccagtg?gtcagtaggg?tcttatatca?atgccgacag??17580
cttcattact?ggtgggtggg?ctcctcaaca?cagctcctgg?tccttaccag?cacacaaagg??17640
ggacctactt?cccattctcc?gggacagcaa?ttctaagtat?gacactcccc?acaccatcca??17700
cctctcccta?ggcactgact?cctttccctc?atccatcaaa?cattaataag?tatcccctag??17760
gataaaagaa?aaagtaaagc?ttctttccgt?gctgctttcc?cctcctaacc?ttcaccaata??17820
aacttctagg?aaaagtaatc?tgtaaatgta?tttatacctg?ctctcatgtc?cccttattta??17880
tttattcatc?caataaatat?tgattgcaag?caccttgatg?tctgtgctca?cctgctcttc??17940
agtcttgcac?cgctgacacc?tagcttctac?gctagtcccc?tgctgtctac?tgagactgtt??18000
tatgtcaagg?ccaccaagga?ccattaattt?gccaaaccag?gtgacctctt?ctcaggcctc??18060
atcctagatg?gttgaccata?gcttatgctc?ttttcttgga?cactaccttc?tcctttttcc??18120
ttgagttcaa?aagtattatt?cttttctagt?tttgccttta?cgtctcaaat?cacctatttt??18180
cagtcctctt?tgcttagttt?cctttccatg?tcttaaatgt?tggtgacttc?aggtatctgt??18240
ctttgacctt?ctagtcttct?ctactcactt?cttagtgaac?catttattcg?tgcttaactt??18300
ccatatgagt?aagatgaggc?aagtgagaag?actgtatcac?aaaacttaag?cagacactca??18360
ctctcaaggt?cctgcaagtt?gcttacatca?cccgagtctc?agacctaaca?gccagaattc??18420
gcttcagtct?tttgtcctga?attctaggac?agatttttgt?cctgaattca?taaaaaacaa??18480
acaaaatacc?ctacctatgg?gcgacttcca?ctggatgtca?aataggcatc?taatattaac??18540
gtatctgaac?tttagctact?tacccttccc?tgaaaactcc?atccaagtga?gaaacatcag??18600
aaacatcttt?gaatcattct?ttctcatcat?ttatgtacag?gtctggagta?ttttagatgt??18660
tacaaataga?agactgtact?tttacaaagc?cacaataggc?agtggggtgg?ggagtgggga??18720
gactgtacaa?acattgatca?ggaaaggcca?agaacctcag?aagctccaga?gatgaaggag??18780
aaagcctcat?gacattaccc?actccttgag?ctttactaat?gccatctcct?gggtcttaat??18840
ggtaccttct?ataaagggtt?tcttcaggcc?ttactttgag?caccataata?ctgcaatgca??18900
attccttttt?tttttttttt?ttgagatgga?gtctcactct?gccaccaggt?tggagtgcac??18960
tggcgcgata?tgggctcact?gcaacctctg?cctcccgggt?tcaagcgatt?ctcctgcctc??19020
agcctcctga?gtagctggga?atacagaggc?gtgccaccac?acccagctaa?tttttgtatt??19080
tttagtagag?acagggtttc?ccatgttggc?caggatggtc?tccatctctt?gacctcatga??19140
tccgcctgcc?ttggcctccc?aaagtgctgg?gattacaggt?gtgagccacc?gtgctcggcc??19200
tgcagtgcaa?ttctgatgtt?ataaccacct?ggagttagtg?caggatttca?ttggttgaat??19260
cctctacaaa?cttcagacac?tagctgcaag?ctctgggatc?cccagaccac?cggcacttct??19320
gaccaactac?ctacaaatct?ggggatctcc?ttaatgccct?caggttcagt?aattcactga??19380
aatgactcac?agaactcagc?aaagtgctac?acttacagtt?atggttttat?tataaaggct??19440
acaaatcagg?accagccaaa?ttaaacacac?acacacacac?acattttttt?tcacattatc??19500
attttcttcc?ctgctgaaaa?ccctttgcca?tttctgtctc?ccttattttt?tgactccctc??19560
aaactcattc?ctaccatctc?ttatcagtct?atcctagagc?ataaaactat?caatctttat??19620
agtgaaggga?accacagaga?tcatgaagct?caactactct?tttcccaggt?gaggaaatag??19680
gaggcaacca?gggcagcaaa?gtgacttctc?cagggtcaca?cagtgaagcg?gtatcaagcc??19740
tgagatcaga?aaccagtctt?cttaatgtta?ttcctgctgc?cctttcaact?ctaccatccc??19800
cttcattctg?tcaccatgct?cctctcttgt?cattccctca?tttgtttgtt?cccatctcct??19860
gtggcaatag?ttctaaacca?agttcagaag?tgaaaatctc?cctaagtccc?aaagcgtcat??19920
gtcagtttga?acaaggtttt?gagctacatg?tgactgaatt?ttgggaaacc?tttaacctct??19980
aagagctcct?ctttggattt?cccctggccc?tttcagcccc?taggtgtccc?agagtctcct??20040
gacaactgta?aggacaagaa?ggcccactgc?ccaagagaat?agggactggg?agcctcctct??20100
cactagcact?gcagagccaa?acttccctct?ctgagcctgc?accctccttc?tgccttctta??20160
gacctcctga?ggcttgcatg?cacgctgaag?cctgatcctg?aactggagat?gtccctacaa??20220
aagtatgtga?tggaaagcat?tttgaagcag?gtattttcaa?aattgaattt?actggctttg??20280
gggatgtcag?ggatctggac?agctggaatt?ttaagattta?agaaaaaaaa?aacagcagct??20340
actagtaaat?agtaaaatgt?tccattaaaa?taaaaagact?tccttttttt?tttttttttt??20400
tttttttgag?acagagtctc?actctgtcac?ccaggctgaa?gtgcagcagc?atgatcttgg??20460
ctcactgcaa?cctccgcctc?ccgggttcaa?gcaattctcc?tgcctcagcc?tcccacatgc??20520
gccaccacac?ccagctaact?ttttgtattt?ttagtagaga?tggagcttca?ccatgttggc??20580
ctgactgatc?tcaaattcct?gacctcaaga?aatctgcccg?cctcaccctc?ccacagtgct??20640
gggattatgg?gcatgagcca?ccacactgag?cctaaaaaga?cattctctat?atgtaggtga??20700
ctgtgaaatt?cattgttcaa?atctcaatac?tttcaaagag?atcattattc?ataattataa??20760
tatgacaaca?ggcataaaat?aggactgcgt?tgccttatat?aattgcgcaa?atgggagctg??20820
ttgcaagcat?ataagaacat?gcgggcaccc?tttctatatg?ccacatagca?gaaagacttc??20880
aagtggatga?acattggtac?actatttctc?caagtcattt?gcattagctc?ttaagttttg??20940
agatttaaca?atgcaggtaa?ttagaatact?ctgagctacc?tccaccctcc?aatattttct??21000
ctttttattc?tcttaatctt?ggttctctca?aatttattat?tccatgtgaa?ttataactat??21060
ctcttatcac?tcaccatatg?ccagtcactc?tgctagttca?tgtatttatt?ctttacagtc??21120
cttggtagat?atttttatcc?tcattttata?tgcatgagaa?aactgagacc?cagagaacac??21180
tacagccttt?cctgaggttg?tcaagtaaaa?gatatagcta?ggatttggac?cctggtctat??21240
ctgacttcta?caatttttgc?acaggctatc?caccctccta?atatatgcct?gctttaatac??21300
ttagtcccat?caaaatgctg?ttgtgtcctg?gaggaaatct?ttgtaacaaa?ggcctgtcca??21360
gtgggtagct?gccttcatag?agtgaattgg?agaggtatca?gaatgcaccc?tgccaccttc??21420
agcccattgt?aaaaacatta?cccctagtgc?ctgcattgct?tgactcttca?tggcttttga??21480
agcttaaaaa?agtcacccca?ttctcccgca?gccattctca?agagatataa?tacattatgc??21540
ttctttaatt?gcaaccagtt?gaaaacaagg?tctttagcaa?tggaatataa?gatggactct??21600
gtgagtcact?gggaaaattc?caggtaggaa?aaatgtttac?ctggtgaaga?ggtacagcta??21660
agagggttga?aaataagacc?aaagacaacc?ttttacaact?ttaccaaaac?cagaccctga??21720
acccaaagaa?gagaagtcct?taaagatacc?gtagtcctct?tttccaagcc?aaaactcaga??21780
atacatagtc?tgacagaagt?tttttattta?tttgtgaatg?attttatttg?aaaaatcaag??21840
gccaggctca?tgcctgtaat?cccagcactt?tgggaagccc?agacaggtgg?atcacttgag??21900
cccaggagtt?caagaccagc?ctggacaaca?tggcaaaacc?tcatctccac?aaaaatacaa??21960
aaattagttg?ggtgtggtgg?cacgtgcctg?tagccccagc?tactagggag?gctgaggtga??22020
gaggatcact?tgagcaagga?gacggagctt?gcagtgagcc?gagattgctc?cactgcactc??22080
cagccttggg?gacagagcaa?gaccctgtct?ctaaaaaaaa?aaaaaagaaa?agaaaaaaat??22140
tagcacattg?gttaattaga?aattattaaa?tctcttttat?aaaaagaata?aaattacatg??22200
aaaccaggac?cttctaggca?attaggaagc?atggctgcat?tattccctat?accaattcct??22260
tctttaatct?agaaaatgtg?tttcacattg?tcgttgaaga?atctgacact?tctgtgctat??22320
ttcggggaga?aagtgcagtg?attttccccc?attgatttgc?tatgtattta?attaacaaaa??22380
ttcagggatg?atgattggca?gggataattt?gggaacactc?tcctttcttt?cttttttttt??22440
tttttttgag?acagagtctc?attctgtcgc?ccaggctgga?gtgcagtggc?gcaatcttgg??22500
ctcactgcaa?gctccgcctc?ccgggttcat?gccattctcc?tgcctcagcc?tcctgagtag??22560
ctgggactac?aggcgcccgc?caccacgccc?ggctacgttt?ttgtattttt?agtagagaca??22620
gggtttcacc?gtgttagcca?ggatggtctc?gatctcctga?cctcgtgatc?ttcccgcctc???22680
agcctcccaa?agtgctggga?ttacagatgt?gagccactgc?gcccgaccca?acactctcct???22740
ttattttccc?tgtgcctgtt?gtgttggaga?gaagagggga?actaaatgaa?atataccacc???22800
accccagaga?ggcaggagag?tgtggcagat?taaatgttag?atgagccaag?cgtgatggct???22860
cacgcctgta?atcccagcac?tttgggaggc?cgaggtgggt?ggatcaccag?gtcaggagtt???22920
caagaccagc?ctgaccaaca?tggtgaaacc?ttgtctctac?taaaaataca?aaaattagcc???22980
aggcgcggtg?gcacacacct?gtaatcccag?ctactcagga?ggctgagaca?ggagaatcgc???23040
ttgaacccag?gaggcggagg?ttgcagtgag?ccgagattgc?gccactgcac?tccagcctgg???23100
gtgacagagc?gagactctgt?ctcaaaaaat?aactaactaa?ctaaataaat?aaataaatgt???23160
tggatgagga?gtctggagat?ttggattcta?gtttattgtg?tccttatgtg?accttgggaa???23220
agctgtgtta?cttctccata?catcagttat?ctaatcggta?aaatggggat?aataatactg???23280
atttcatttt?gtttgaacgt?agagtaggac?agaatgtgaa?aacattccag?aagataccta???23340
atgaaaatgg?aagtttgaat?tacatagcat?gctattctta?tccctaacta?taaaaataag???23400
agagccaaac?tcccagatgg?catctgtgga?cctgcctggg?gcctggagga?actcatcacc???23460
ctgaagggaa?agacacaaac?ctggctggct?ttgcacctgc?tgattgtaga?gtgctagagc???23520
cttgaacaaa?aataggtggt?agcctggtag?tagtcacagt?gggccttggg?caatatccag???23580
tgctgtgcta?gcttcaggtc?tgacccagtg?cagtctcagt?gatggtagcc?acaagggtgc???23640
ttgtgtgacc?ccacccccag?ctccaagcag?ctcagcacag?agaaatagag?actccatttg???23700
tttgggagaa?agtaagggaa?gagaacaaaa?gtctctgctt?ggtaatccag?agaattcttc???23760
tggatcttat?ttaagaccac?aaaggtggta?cctctataag?tctgcaagaa?ccatagcatt???23820
actgcacttg?cggtgctctg?taatatagat?atggcttaga?tcacaacacc?caagtttttt???23880
tgaatatatg?gaaagccttc?ccaaggaggg?caggtacaaa?cagtcctaaa?tgtcaaagac???23940
tacaataaat?acctaactct?tcaatgtcca?gacactgacg?aacttccaca?agtatcaaga???24000
ccatccagga?aaacatgacc?tcaccaaagg?aactaaataa?ggcaccaggg?tggagagaca???24060
gagatatgtg?acctttcaga?caggtaattc?aaaaaagctg?tttgaggaaa?ctcaaagaaa???24120
ttcaagataa?cacagagaaa?gaatttagaa?actttcagcc?atgttaacta?agaacagaag???24180
agaaaagacc?caaataaata?aaatcagaaa?tgaaagagga?gacattacaa?ctgataatac???24240
agaaattcaa?aggatcattg?gtggctacta?tgagcaatta?tatgccaata?aattggaaaa???24300
tctagaagaa?atgtataaac?tcctatacac?atacatccta?ccaatattgg?accctgaaga???24360
aatctaaaac?ctgaacagat?aaataacaag?taacaagatc?tgggacccga?agtattcact???24420
gctgaattct?accaaagact?tgaagaacta?ataccaaccg?tactcaaact?actctgaaac???24480
atagaagagg?agggaatact?tccaaactca?ttctacaagg?ccagtattac?cctgatacca???24540
aaaccagaca?aaagtacatc?aaaaaaagaa?agctacaggc?cagtatctct?gatgaatatt???24600
gatgtaaaaa?tcctcagcaa?aatactagca?aactgggttc?aacaacatat?taaaaagatc???24660
atccatcatg?atcaagtggg?atttatccca?gggatgcaag?ggtggttgga?catatgcaaa???24720
tcaaacactg?tgatatgtct?tatctacaga?atgaaggaca?aaaaccatat?tatcatttca???24780
gttgatgctg?aaaaagcagt?tgataaaatt?caacatccct?tcatgataaa?aattcccaaa???24840
aaactgtgta?tagaaggaac?atacctcaac?ataagaaaag?ccatatagaa?tagaccgacc???24900
actagtatca?taatgaatag?ggagaaacta?aaagcccttc?ctctaagatc?tagaacacaa???24960
ggatgcccac?tttaccactg?tttttcaaca?taatactgga?agtcctatgt?aatcagacaa???25020
gagaaagaaa?gaaatggcat?acaaattgga?aaggaagaag?tcaaattatc?cttgttttca???25080
gatgatctta?ttatatttgg?aaaaacctaa?agactccacc?aaaaaaccat?tagaactgat???25140
acacaaattc?aacaaggtca?cagtatacaa?aatcatcata?caaaaatcag?catttctttt???25200
tctttctttt?tctttttttt?tttttttgag?acggagtctc?cctctttcgc?ccaggctgga???25260
ctgcagttgc?gctgtctcgg?ctcactgcac?gctccgcctc?ccgggttcac?tctattctcc???25320
tgcctcagcc?tcctgagtag?ctgggaccac?aggcgcccgc?caccacgccc?cgctaatttt???25380
ttgtgttttt?aatagagacg?aggtttcacc?gtgttagcca?ggatggtctc?gatctcctga???25440
cctcgtgatc?cgcccgcctc?ggcctcccaa?agtgctggga?ttacaggcgt?gagccaccgc???25500
gcccggccca?aaaatcagca?tttctatatg?ctaacaggga?acaatctgaa?aaagaaatca???25560
agaaagtaat?cctgttaaca?atagctaaaa?ataaaataaa?gtacctagta?attaaccaaa???25620
gaagtgaaag?atctctaccg?tgaaaactat?aaaatgttga?cacaagaagt?tgaagaggcc???25680
acaaaaaaaa?aatgaaagat?attccatgct?tatagattgg?aagaatgttc?atactaccca???25740
aagcaatcta?cagattcaat?gcaataccta?acaaaatacc?aatgacattc?ttcacagaaa???25800
tagaaaaaaa?aaattctaaa?atttacatgg?aaccacaaaa?gacccagagt?agccaaagct???25860
atctgaagca?aaaagaataa?atcaggagga?atcatattat?ctgacttcaa?attataccac???25920
agctatagca?acccaaatag?catagtactg?gcatgaaaac?agacacatag?accagtggaa???25980
cagaatagag?aaacaagaaa?taaactcata?catctacagt?gaactaattt?ttgacaaaag??26040
agccaagaat?ataaaggaaa?agacaatccc?ttcaataaat?tgtgctggga?aaactggata??26100
tccatatgca?gatgaatgaa?actagactcc?tatctcttgc?tatatacaaa?aatcaagtca??26160
aaatggactt?tgagacatca?aaccatgaaa?ctactacaag?aaaacattgg?ggagactctc??26220
aaggacattg?gagtgggcaa?agatttcttg?agtaataccc?cacaagcaca?ggcaaccaaa??26280
gcaaaaatgg?acagatggga?taacatcaag?tgtttttttt?ttttagaatt?attttatcag??26340
ataaaaaatt?agtttcattg?atgagttttt?ttaatctttt?atttttatat?ttatttattt??26400
atttttatta?tacttttaag?ttctagggta?catgtgcaca?atgtgcaggt?ttgttacgtt??26460
atgtatacat?gtcccatgtt?ggtatgctgc?acccattaac?tcatctttta?cattaggtat??26520
atctcctaat?gctatccctc?ccccttcccc?ccagcccacg?acaggccctg?gtgtgtgatg??26580
ttccccaccc?tgtgtctaag?tgttctcatt?gttcaattcc?cacctatgag?tgagaacatg??26640
tggtgtttgg?ttttctatcc?ttgtgatagt?ttgctcagaa?tgatggtttc?caacttcatc??26700
catgtcccta?caaaggacgt?gaactcatcc?tttttatggg?tgcataatat?tccactgtgt??26760
atacatgcca?cattttctta?atccagtcta?ccactgatgg?acatttgggt?tggttccagg??26820
tctttgctat?tgtgaatagt?gccacaataa?acatacatgt?gcatgtgtct?ttatagcagc??26880
atgatttata?atcctttggg?tacataccca?gtaatgggat?ggctgggtca?aatgatattt??26940
ctagttctag?atccttgagg?aatcgccaca?ctgtcttcca?caatggttga?actagtttac??27000
agtcccacca?acagtgtaaa?agtgttccta?tttctccaca?tcctctccag?cacctgttgt??27060
ttcctgactt?tttaatgatt?gccattctaa?ctggtgtgag?atggtatctc?attgtggttt??27120
tgatttgcat?gtctctgatg?gccagtgatg?atgaacattt?tttcatctgt?ctgttggctg??27180
cataaatgtc?ttcttttgag?aagtgtctgt?tcatatcctt?tgcccacttt?ttgatggggt??27240
tgtttgattt?ttttcttgca?aatttgttta?agttctttgt?agattctgga?tattagccct??27300
ttgtcagatg?ggtagattgt?aaaaattttc?tcccattctg?taggatgcct?gttcactctg??27360
atgatttctt?ttgctgttca?gaagctcttt?agtttaattg?gatcctgttt?gtcaattttg??27420
gtttttgttg?ccattgcttt?tggtgtttca?gtcatgaagt?ccttgcccat?gcctatgtac??27480
tgaatggtat?tgcctaggtt?tcttctaggg?tttttatggt?tttaggtcta?acatttaagt??27540
ctttaatcca?tcttgaatta?atttttgtat?aaggtggaag?gaagggatcc?agtttcagct??27600
ttctacatat?ggctagccag?ttttcccagc?accatttatt?aaatagggaa?tcctttccct??27660
atttcttgtc?tttttcaggt?ttgtcaaaga?tcagatggtt?gtagatgtgt?ggtattattt??27720
ctgagggatc?tgttccattc?cattggtcta?tatttctgtt?ttggtaccag?taccatgctg??27780
ttttggttac?tgtagccttg?tagtatagtt?tgaagtcagg?tagcatgatg?cctccagctt??27840
tgttcttttt?gcttaggatt?atcttgacaa?tgcaggctct?tttttggttc?catatgaact??27900
ttaaagtaga?tttttccaat?tctgtgaaga?aagtcattgg?tagcttgatg?gggatggcat??27960
ggaatctata?aattaccttg?agcagtatgg?ccattttcat?gatattgatt?tttcctatcc??28020
atgagcatgg?aatgttcttc?catttgtttg?tgtcctcttt?tacttcgttg?agcagtggtt??28080
tgtagttctc?cttgaagagg?tccttcacat?ccctatataa?gaagctgtaa?cagctctata??28140
gaaaaaaatc?taataatctg?attaaaaaat?gggtaaaagg?tctgaataag?gccaggcgca??28200
gtggctcaca?gctgtaatcc?cagcactttg?ggaggccgag?gtgggcaagt?cacgagatca??28260
ggagttcaag?accagcctgg?ccaacatggt?gaaaccccgt?ctctactaaa?aatacaaaaa??28320
attagctggg?cgtagtggtg?ggcgcctgta?atcccagcta?ctcaggggct?gaggcaacag??28380
aatcacttga?acccaggagg?cggaggttgc?agtgagatga?gatgtgccac?tgcactccag??28440
cccaggtgac?agagtgagac?tccgtctcaa?aaaaaaaaga?tcgaaataga?catttctcaa??28500
aggaagacat?acaaatggca?aacaagtatg?tgaaaaatat?gtgaaaaggt?gcacaacatc??28560
accaatcatc?agataaatga?aaatcaaaac?tacaataaga?ttatcatctt?accccagtta??28620
aaatgacttt?tatccaaaag?acaggcaata?acaaacgctg?gacaggatgt?ggaaaaaagg??28680
gaatccttgt?acactgttaa?tgagaaagta?aattagcaca?gccaccttgg?agaacagttt??28740
gaaagttcct?caaaaagcta?aaaatagagc?taccatacaa?tctagaaatt?ctactcctag??28800
atacatactc?aaaagaaaag?aaatcaatat?attgaagaga?tacctacact?cccatgttta??28860
ctgcagtgct?attcacagta?gtcaagactt?ggaagcagct?taagtgtcca?tcaacagaga??28920
aatggataaa?gaaaatgtgg?tacatataca?caacgaagta?ctattcagcc?ataaaaaaaa??28980
tgagatctgt?catttgcaac?aacgtggatg?gaagtggagg?tcattatatt?aagtgaaata??29040
aaccaggtat?agaaagagaa?accacatgtt?ctcacttatt?tgtgggagct?aaaaattaaa??29100
actattgggc?tgggcatggt?ggctcatgcc?tgtaatccca?gcactttggg?aggccaaggc??29160
aggcagatca?tgaggtcagg?agttcgagac?cagtctgact?aacacagtga?aaccccgtct??29220
ctactaaaaa?tacaaaaatt?agccaggcat?ggtggtgcat?gcctgcaatc?ccagctactc??29280
tggaagctga?ggcaggagaa?tcgcttgaac?ccaggaggca?gaggttgcag?tgagccgaga??29340
tcgcgccact?gcactccagc?ctgagcaaca?gagcgagact?ccgtctcaaa?aaaaaaaaaa??29400
aaaaaaaatt?aaaatgattg?aactcatggg?ggtagagaat?ataaggatgg?ttaccaaagg??29460
ctgggaaggg?tagtggggga?tgaggaggaa?ttgggggtgg?tcaatgagta?caaaaaaaga??29520
gaaagaatga?gaaagaccta?gtatttgcta?gtacaacagg?gtaactatag?taaaaaataa??29580
tttaatcatt?gatatggttt?ggatttgtat?cccctcccaa?atctcatgtt?gaattataat??29640
ccccaatgtt?ggtggagggg?actggtagga?ggtgattgga?tcataggggt?ggattatacc??29700
cttgctgttc?tcgtgatagt?gaatgagttc?tcatgggatc?tgattgttta?aaagtgtgta??29760
gcactccccc?tgctctcctc?tggccatata?agaagtgcct?gcttctcctt?cgtcttctgc??29820
catattataa?gtttgagtcc?tccccagcca?tgcttcctgt?acagcccatg?gaactgtgag??29880
tcaattaaac?ctcttttcct?tgtaaattac?ccagtatcag?gtagttcttt?ataacagtgg??29940
gagaacggac?taatacaacc?atacatttta?aaaataacta?aaagagtata?attggattgt??30000
ttgtaacaca?aaggataaat?gcttgagggg?atgaataatc?catttaccct?gatgtgatta??30060
ttacgcattg?catgcctgta?tcaaaatatc?tcatgtaaca?caaaaatata?tacatctact??30120
atagacctac?aaaaattaaa?aaattttaaa?tttttttaaa?aataggagag?ccaaaaagaa??30180
cagtagttat?ttcccttatt?gcaatggctc?atattggcat?gaggaagcca?gcagttgggg??30240
taatggagtg?gttgctggcc?aaaaattagc?acatgcataa?gtccccactg?gaagagaggg??30300
attttgatta?tatttccatc?tgctccactt?caggcatgct?ggctctgtca?tgttgtacct??30360
cacccattct?gaggtagaca?ttccctagat?gatttcgggt?atgaggtggg?ggcggtgttg??30420
ggggagggat?ccactgccaa?ggacacctac?agaaagctgc?tctctacttt?gcagattgat??30480
aacaaacagc?ttcagggcta?tttatctgag?cttcgcccag?tgacgattgt?gtttgtgaac??30540
ctgatgtttg?aagaccaaga?caaagcagaa?gagataggcc?cagccatcca?ggatgcctat??30600
atgcacatca?cttctgtcct?gaagatcttc?caaggccaaa?tcaataaagt?cttcatgttt??30660
gacaaggtaa?gtgtgaacta?tgggatggga?acctaccaat?agttttaggt?tagcattcat??30720
ggacaagcac?attggtgaga?atagacacag?gaaatttaac?ctagaggctg?ggcgtggtgg??30780
ctcacgcctg?taatcccagc?tctttgggag?gcagaggtgg?gcggatcact?tgaggtcagg??30840
agttcaagac?cagactggcc?aacatagtga?aaccctgtct?ctactaaaaa?tgcaaaaatt??30900
agctgggtgc?ggtggcacgt?gcctgtaatc?tcagctactc?aggaggctga?ggcaggacaa??30960
tggcttgaac?ctgagaggcg?gaggttgcag?tgagccgaga?tcgcaccact?gcgctccagc??31020
ctgggctata?gcgtgagact?ccgtctcaac?taaacaaaaa?aagaaattta?acctagaagg??31080
ccagtctttg?tttataatta?taacttctat?ggtggatatg?gcacttacta?tgtgccaggc??31140
actgttctca?ggacctgatc?tctattgact?catttcatcc?tcatgaccac?tctgagcagt??31200
aggttgctct?tgtcattatc?ctcattatat?agatgaggat?gctgaaacac?agattaggat??31260
accaggacaa?ggcgagatta?cgttttgctt?atgatcatca?agctagtaag?ggggaggctg??31320
ggattcaaac?ccaggcagtc?tgccatcccc?gtctgagctc?actatgctgg?gctacctctc??31380
actacgctgg?gctacctctc?actacacata?agtctccagc?tcagtgcatg?atgtattacc??31440
caggggtttc?aggtcaggag?tctttagtaa?ccatcttacc?ccagaagctt?gtttccaaga??31500
aagcccactt?gccatgtcaa?cacctccagt?tcccctttta?ttttcatcca?tggcagggag??31560
gggactgcct?ctggctccca?ggtgttttcg?ctctgttctt?tttttttttt?ttttttttga??31620
gacggaatct?tgctctattg?cccaggctgg?aatgcagtgg?catgatctcg?gctcactgaa??31680
acctccgcct?cccgggttca?agcgattctc?ttgactcagc?ctcctgagta?gctgggatta??31740
caggcatgcg?ccaccacacc?tggctaattt?ttgtattttt?agtagagatg?aggtttcgcc??31800
atgttggcca?ggtgggtctc?gaattcctga?cctcaagtga?tccacctgcc?tcggcctccc??31860
aaagtgctgg?gattacaggc?atgagccact?gcacctggtc?ttcactctgt?tcttaatcaa??31920
ttcagagaaa?agtgatgtga?tgaacaaatg?accacagatg?catatgtgag?aattgatttc??31980
ccatctcaat?tccttttgtg?tattaaaagc?agagcactta?attactgccc?cacatccact??32040
cactcactaa?ttcaacaagc?atttactgag?catttcatag?aagacgaaaa?gctagggctg??32100
ggcagcagag?atgagtaaca?catatattga?cacaaccagg?caggaagcat?gcattctata??32160
tgagacgaac?taactctgtg?ctatgggagt?tctggaaagg?gattacttcc?agcctggtgt??32220
ctccagtacc?ttcttcaata?ctgacccatg?ggtatcataa?gaaaagagtg?tagaatctaa??32280
gagaacagtc?tttcgtgtct?tgcagacatg?gctccaaaga?ttcccagctg?tgagacttag??32340
caagtcattg?aacttctctg?agccttggtt?tattcctctt?tgaatgggga?tagtatttgt??32400
ctcaaatgat?tgtggaaagt?tttaaataat?gtaatatgtg?tgaggcactt?ggtgtaatgc??32460
ctatcttaga?gtcagtgtgc?aataaatgag?agctgtcatt?ccattgctag?ggggaatcaa??32520
aagctcttgc?caggccgcta?cataaatttg?caggcaaaag?ctccctgctt?cccccaaagg??32580
ggttgccctc?tttgcacgta?cctagaagca?gtgtttcccc?cttcatgtca?aggcagatcc??32640
cagtcctttt?taagatctaa?cagttgatca?aattcttttg?gagagggttg?aagaaattga??32700
ggtattttag?tgttctttgc?attttatcag?gatgtaacat?gtcaaaaact?caaaatttca??32760
acccatcacc?ctttattcac?aatgcccttt?tcttacagac?aacagcacct?gactgaggtc??32820
attttttaag?tgactaatac?tacaaatgcc?aagttttaga?gttgaatcat?tgcatggaac??32880
agttagcttt?atgataagaa?aacctactta?cagcctaagc?ctttatccct?aagaataaca??32940
gtatctgcaa?agtactttat?agtttaggat?gactttttga?atatatataa?cacattaatt??33000
cttttagtag?ccaaaaacat?ctcagcaggt?ctacagtata?tccattttca?gagagataaa??33060
cggaagttcc?tagattgtaa?tagacttatc?taagtttcca?cacttgagaa?gtggcttgag??33120
gacagagact?ttctgattcc?agagctggtg?ccttttccac?tgctctgtgc?tgctgcttca??33180
tagacttaaa?ctgagcactt?tgcagcatgg?accttggcca?caggagagag?taggccgaag??33240
catgcacaca?gatagctcag?ccctattcac?tatatctgga?gcaaaacaag?cccttctcaa??33300
ggctcaagcc?ctcctgttga?tgatgcagta?gaagtgtttg?aagtgtacta?aaaataaaat??33360
actgtgagag?aaatcatgat?aaaatctgat?tcagaagcca?aaaattgccg?ccggctctct??33420
gttgagcctt?ctggccagtc?cagtttaaag?cacactgtcc?atcagctgtg?gttgctgtct??33480
ctctccctca?cagggctgct?ctttcctctg?tgtctttggc?ttccctgggg?aaaaggtacc??33540
tgacgagctc?actcatgctc?tggaatgtgc?tatggatata?tttgacttct?gctctcaagt??33600
ccacaaaatc?cagtgagtat?tgaccctggt?cccacccagc?ggtccctgac?ccttttgagg??33660
cataagtagg?gagggcatgc?agggaacagg?aaagaaagaa?gaattaatta?agaacttagt??33720
cctgtgtctc?aaactgttgt?tcctccttcg?catctccggg?ccatgtagaa?atgccataaa??33780
ctaattccaa?cgggtagaga?aaatcctttc?ccaccctttc?ccaacccaga?cattatttcc??33840
cacccttccc?actttctcta?cgctcattat?ctttatttct?ttccccacaa?atcttgtctc??33900
ccctgcacca?gaactgtatc?catcggtgtt?gccagtggga?ttgtcttctg?tgggatcgtt??33960
ggacacactg?tgagacacga?gtacacaggt?gtgctgggtc?agctcatctc?cagctttctt??34020
tctgcaaaca?cagcaccttg?ccactgggct?ttgcgggagg?aagcacaaaa?atgagtgaga??34080
catgagccct?gccctcagaa?actttagagt?cttccagatg?gagccaagcc?atggagccct??34140
caatgcttgc?agagtgtgca?tttctggggc?tatgtatgag?tagagaaata?tgtagtcatg??34200
agaggggagc?agtgggaggc?tatatgttga?tggaatgagg?ggctcctgta?atactttcct??34260
gttaacatta?aatagttact?tctcttaatt?cctggaataa?gctagaactc?cttaaaaatt??34320
atgaatgttg?atattactga?aaaataatga?cactctcaaa?agagagtagt?aataagtaaa??34380
tcttatctcc?agatttcaca?actctattac?ttcccttttc?catcctatca?gggtttaaga??34440
ttttcagcaa?taatgcatct?aaaatactga?atatatgtaa?aataccacga?tagttatgtc??34500
tgaaatgata?caatgtctga?gatgttcttc?aaaagtacac?agggtgggga?gtgtatgggg??34560
gtgaggatgg?ggcaggatta?gccatgggct?aatggcttgt?tgggatgggg?tgatgggtat??34620
atggaaattc?attatatttt?attttatggt?caaatttctc?cacaataaat?agttttcaaa??34680
aagagtacct?tgttcagaag?tattcaagtt?tatgttaaag?tgacacattt?gctacctcat??34740
ttgtagtaat?attaattgaa?ggcttacaag?cagccagctg?ctgttgaaag?tgataaacgt??34800
gtattaacta?attaatcttc?ataaaccacc?ctctcagaga?gttactatta?tcatccctat??34860
tttataggtt?agagaatgga?ggcatgagga?gttatttaaa?gtaattgtcc?caagtagttt??34920
gcacatagtt?aggggtagag?ctggtgttca?accctgcaca?gtctgccttc?agagcctgtg??34980
cttcaatcct?ccatgcacgc?ctcttctagc?ccatttacta?aatcgagaaa?tcgccaaatg??35040
aaggtttatt?cataggagca?tgcagacaca?attttatgtc?tcatatggag?atcagtaccc??35100
caggcccaag?catgtgcttg?tccaccttgt?ggcagaagac?caactgacac?cttctctgag??35160
agccttcagt?gctgtggcca?tcccacttac?agagcctgct?ccatactcaa?gccccttcca??35220
tccctgagca?ggtcattctc?ttgacctccc?aagtgaggca?gaaactttgc?taatggctaa??35280
ctaactccct?gcacattttg?tgaatagcca?ttggctgaat?atgggtcttg?agactaggct??35340
tctgtgtcac?tcatgaacag?caaagggagt?aaagggtaaa?aatgctattt?ggggacaatg??35400
tttcagatta?cattcagttc?aatgcctgtt?atttccctga?tctttgactt?tctctttctt??35460
gctatagtca?ttggtcaaaa?agtcaactta?gctgccagga?tgatgatgta?ctacccagga??35520
attgtgacct?gcgactctgt?cacctacaat?gggagcaacc?taccagcgta?cttttttaaa??35580
gagcttccaa?agaaagttat?gaaaggtgtt?gcagattctg?gaccattgta?tcagtattgg??35640
ggccgtactg?agaaagtgtg?agtgtggagc?attaattttg?aagtatattt?tagtaaagaa??35700
gcgggagaat?tatgatagca?aagcagtcac?ccatttaaga?tttggagcca?gttcaaaaag??35760
ttgaaatcta?tgctttcccc?agaccaaggc?ccagacttca?aaatccttaa?tctttcctcc??35820
atctgactga?cactatggca?tggtggaaaa?tcccattctc?tcctcagatc?tgagaatatg??35880
agggtaattc?ttcaaaggtt?gtacaaacca?aacaaaaaat?cctctcattt?gagtatctat??35940
ttgcacccaa?atgggcccaa?tcaccaacca?tttaatatta?tttactaatt?atgtcaactg??36000
tatgccgagg?cattgttagg?gttaaaagag?tataagatat?tatttctcct?ctaagtcttt??36060
agtgaaatac?attccccaaa?agctcagcat?agatttatgg?gtgtcacttt?gaagcttaaa??36120
atccttcaat?ggctttcagt?cattttcatg?gtgatgttca?aaatctttgc?agtgacatac??36180
aaggtaccac?ctgcctttcc?aacctcatct?cctcctgttc?cccctcctct?gggttgttta??36240
agtagattgt?cctcatcagc?acccacctaa?tcctggtcta?ttgggaaaac?cgcagtcaat??36300
ttttgaaacc?cagctcgagg?gattcataga?cattcctcta?tgaattcccc?atcccagcta??36360
gacagttaag?ctctttcccc?ctttgtcttc?cttcttcctc?ttcctttttt?cctcctatag??36420
catatgcttc?tattagaaca?ctccttgccc?tatatcacaa?ttattcactt?cctacagttt??36480
tcacttgtta?cactgtgaac?tctttgaaga?tactaattat?ttctttattc?ttatatcccc??36540
agtgcttggt?atacagtagg?tcctcaataa?tgatgaataa?atgaatggca?cagagagcag??36600
aaagttgtta?ttcattagat?tagcaagctg?gaatcgaggt?cttcaagagt?cagataacag??36660
aaccagggct?gcagttgggt?caaggtgtct?ttattattcc?cttcagtatt?cctgaggctt??36720
agcactgtgc?ttggcataca?taggccatca?ataaagtgca?gtttgaatac?atgaatgaat??36780
aataattttt?agtgagtact?tattaaacat?caggtacttt?acctcaaaat?atataatcca??36840
gtcttaatat?tgaccatacg?agatagaaac?tattataatt?tccattttat?aaattcaaaa??36900
actgaggctc?agagatgtta?aatgacttgt?ctatggccat?atctatagtg?agcaatggag??36960
tcaagattca?gtcacaataa?tgtgacctta?cgggcaatca?caaaacttca?gtggtgtgca??37020
aaaataaaca?tttatttttc?tcacaaatgt?ggggttcaat?tgatcttggc?tggatttggt??37080
tgatcttgtc?ttggcttatt?cacgtgcctg?gggttcaaca?gactgttggc?caacctggcg??37140
gcctcagttg?ggataactag?ggcaatctgg?ctctatgtgt?ctcatcttcc?atccagcatg??37200
tttgtcctgg?caatactgga?ggagcaagag?agcaggccca?atgcaaaagc?atttttcaag??37260
cctcttccta?tgtcttatgt?ttgcagatag?tccattgaca?aaagcattca?caaggctgag??37320
tccagaatga?gaggactctg?ccaagttaca?cagcaaaggg?cacagataca?ggtactgggg??37380
ccattaatgc?aatcagttta?ctatgcaaac?ccaggactat?ctgatcccaa?agcctgtact??37440
cttcatgatt?tttctgtacc?acctctgcag?ataaaagtgg?agaaatacac?acacagtatg??37500
aacagggcct?agttcctgcc?cagaaaactc?acaatcaagt?ggggaagacc?aacatacaca??37560
aacttagctg?tatgttacat?gggaaccttt?gatatatgct?ataagagagg?cataacaaag??37620
tagtattgta?gttcagagaa?gggcataatc?cattttgact?aaaaggcttc?ttcaagagat??37680
agtgttatgg?agtgagcaaa?catatgcacc?ctggcctatg?tttggatact?gtcagtatcc??37740
tgtgttacca?cctgctatgg?ggtcttgggc?aattaaactc?tttgtgcctg?aatttcctca??37800
ctggcaaaat?gaacataaga?gtagtacttt?tttttttttt?tttttgagat?ggagctttgc??37860
ttttgttgcc?caggatggaa?tgcaatggcg?tgatcttggc?tcactgcaac?ctctgtctct??37920
tgggttcaag?cgattctcct?gcctcagcct?ccagagtagc?tgggatggca?ggcgcaagcc??37980
accacgccca?gctaattttt?gtatttttag?tagagacagg?ttttcaccat?gttggtcagg??38040
ctggtctcaa?actcctgacc?tcagatgatc?cacctgcctc?ggcctcccaa?aatgctggga??38100
ttacaagcat?gagccaccgt?gcctggccag?tagtcctttt?ttttcttttt?gagatggagt??38160
ctggctctgc?tgcccacgct?ggagtgcagt?ggtgcgatct?cggctcactg?caagctcccc??38220
ctcccgggtt?cacaccattc?tcctgcctca?gccccctgag?tagctgggac?tacaggcaac??38280
cgccaccatg?cctggctaat?ttctttttgt?atttttggta?gagacggggt?ttcaccgtgt??38340
tagccaggat?ggtctcgatc?tcctgacctc?gtgatctgcc?cacctcggcc?tcccaaaggg??38400
ctgggattac?aggcgtgagt?cactgcgccc?agccaagtag?tacttcttaa?cagtgttttt??38460
gtcaggatta?aagaaaatga?tgcatgtaaa?gcacttggaa?ctgcgccaga?cacatagcat??38520
gtgctccaat?aaaaggcgcg?ctattattgt?ttgagcaatt?ggtggaatct?ttgcaggatg??38580
tgtgactctg?caccacattg?aaatctactg?ggtcgtatat?caggtgtctg?atctccccag??38640
aaaggggttt?ctctaccagt?gcagactcaa?cagcatttat?tgaacaatgt?gccagatgct??38700
atggaaacag?atgctacctg?agttctttgg?attctccact?accaagtcag?accttctcgt??38760
ttctccttct?tttggcgttt?gcgacccgtg?agtcagggga?tagactcttg?ttagcaattg??38820
agaaggaaac?tttctgggaa?ctaagaacta?atcactcttg?ctctcaatat?gtccctgttt??38880
tgaatctagc?atctgttctt?ttgttcttct?cttcagcatg?tttggtatgg?cgtgcctcat??38940
ctgcaacaga?aaggaggatt?accctttgct?gggtaggtag?taggccttga?ttttaaactt??39000
ctttattgaa?ctaaaacaaa?acatgcagaa?aagtacatca?atgataactg?tgcagcttaa??39060
tgaattatca?caaaatgaaa?atataatcat?catccaggtt?aagaaataga?aaaatagcaa??39120
tacaccagga?ttactctttc?cttcttcctt?tccccaaagt?cttctaacac?cctcgattac??39180
ttatgcctgt?ttaaaaaatt?gatacagatg?gaatcataca?ttgtataatt?atatacggct??39240
tatatatact?ttctcttact?caatggtatg?ttatataatt?catccatatt?gttgggtgta??39300
gctgtaattt?attctatgtc?attactatgt?agtattccat?ttttataaat?atacaacaat??39360
ttacccattc?tgttgctgtg?caacatttgg?gttatttcca?gtttttggtt?cttatgaata??39420
atattgccat?aaacattctt?acacaagtct?tttggtgaat?gcatgtatgc?atttctgttg??39480
agtacaaggt?aggagtaaaa?cgtaggactg?aaattgttgg?gacaaagggt?gccaaatagt??39540
tttccaaaat?ggttgtattt?atttatattc?tgactgagaa?tgttaagaga?gttccagttg??39600
ttcttcatct?ttggcaacaa?cttagtttta?tcaatcttta?tcctttcaat?aattctgttg??39660
ggtgtatagt?ggtatcttat?tatggtttcc?atttgtattt?ccctgatgtg?gttgagctcc??39720
ttcttcataa?gtttattggc?catttggatt?tatttattta?tttatttatt?ttgagacaga??39780
gtctcactct?gttgcccagg?ctggagtaca?aaggagcaat?cttggctcac?tacaacctct??39840
acctcctggg?ttcaagtgat?tctcaggact?cagcctcctg?agtagctggg?attacaggtg??39900
tccgccacca?tgcccagcta?atttttatat?tttagtggag?gcagggtttc?accatgttgg??39960
ccagactggt?cttgatctcc?taacttcaag?tgatccactt?gccccagcct?cccaaagtgc??40020
tgggattaca?ggcgtgagcc?actgtgccca?gcccagacat?ttttttaaag?tacctgtaca??40080
atttttcacc?tatttttcaa?ctgggttata?ttttgattat?cttttggaat?tatttacaca??40140
ttctagagat?gggtcctttg?tcatttgttt?ctactgtata?tcacttttcc?cactctgtgt??40200
ttgccttttt?actctcaatt?atgcatttaa?taaacagaat?tcttaacttt?aatgtaatca??40260
aatttacctg?tcttttatag?ttagtgcttc?tgtatactat?ttgagatacc?tttccttacc??40320
caaaaatcat?ggagatattt?ttctagcatt?tttttcagaa?attttgtttt?taccttttat??40380
atttaagtct?acaatccatt?tggaattgat?atttttgtga?ttcctggtga?tagggacctt??40440
attgtaagaa?agataactcg?agattagaca?ggggagtaga?cctaaaatga?ggaagggata??40500
tacctataag?agaagagacc?caaagaagat?tgacctgtgg?attctgaagg?cagccacttc??40560
tagtagcact?tgtaatttcc?ttctgtcaga?cacgaacatc?cccaaaagtc?ttatcataag??40620
ttaaatcttg?gtcctaactg?tgtcaaggca?attaagagga?ggctctgtct?cacactttgg??40680
agaaatattg?ggccacaatc?ttggtgtcag?cagagcctga?aggagggcaa?cagttccaga??40740
actgcaaaaa?aacacttggg?ccagcagaaa?tgcctcactt?tcactgcttt?caggtagttt??40800
tcagggtctt?caagccaatc?acttcattta?agtccagatt?ccaaaactcc?tgaagctaga??40860
gagaaggaat?acccactctc?accctcctca?gaggccttac?ttttcatcct?aggatatact??40920
tattttacta?actgacagca?acagaatcct?aaccttcttt?ctacaagatt?gcagacccaa??40980
catgacagtc?acattagaac?acattatgtg?gatatttctt?ttttttttct?tttgagacag??41040
agtctcactc?tgtcgcccag?gctggagtgc?agtggcgcga?tctcagctca?ctacaacctc??41100
tgcgtcccgg?gttcaagcga?ttcttctgcc?tcagcttccc?aagtagctgg?gattacaggt??41160
gcacaccacc?acacccagct?aatttttgta?tttttagtag?agacggggtt?tcaccatatt??41220
ggccaggctg?gtcttgaact?cctgatctcg?tgatctgccc?gccttggcct?cccaaagtgc??41280
tgggattaca?gacgtgagcc?actgcgtgca?gcctatgtgt?atatttctca?gtctgatcta??41340
gttgcccttt?tgcactgatt?ccaccagtat?gacataaaga?tcaggtccac?atacctttcc??41400
ttcaagctat?aaccaaacac?agattgtcag?aggctagcag?catgggaaat?gcccttcttt??41460
tacaagggct?gctataaatg?aaattgcaac?agcatggttg?acaacaaaac?tataataaat??41520
aaatagtggc?tttttagggt?aaaaactgca?tacaacagtc?cccgatattg?aggctttgct??41580
tagatagaaa?caaggtgcat?gcatttcaag?ttaaggagac?aatctcattt?tagaatccag??41640
ctaaagatac?tccataaggt?tctaccagta?ggtgttctgt?atgaatagaa?cacagggagc??41700
tggaagagtc?agctatgcag?gctttttttt?tttttaagct?tccttaggaa?actttatttt??41760
ttttgagatg?gagttttgct?cttgttgccc?aggctggagt?gcaatggcgc?catctcggct??41820
tactgtaacc?tccgcctccc?aggttcaagc?aattctcctg?cctcagcctc?ctgagtagct??41880
gggattacag?gcatgcacca?ccacgcccgg?ctaattttgt?atttttaata?gagacggggt??41940
ttctccatgt?tgaggctggt?ctcgaactcc?tgacctcagg?ggatccaccc?gcctcggcct??42000
cccaaagtgc?tgggattaca?ggcgtgagcc?accgctccca?gcctggaaac?tttattattt??42060
tttatttatt?tattttttat?tattatactt?taagttctag?ggtacacaat?gcacaacgtg??42120
caggtttgtt?acatatgtat?acatgtgcca?tgttggtgtg?cagctatgca?gcctttgaag??42180
cctcatcttc?taagttccta?tgtgagcttc?attcaggcca?aagaaaaaca?caaaacatct??42240
cacgaaattg?aggttcaaat?gcattttcag?aaagggaata?tttcacccaa?aagaagcaat??42300
acagtctgct?aagtagttct?cactaagcca?tactcagaaa?tgtatattac?caagcaaagc??42360
acttagcttc?tttttattaa?atgtctacac?ttgaattaat?ggtccttcaa?caaagacatt??42420
agataatacc?tggatattta?tttgttctat?cagtgaataa?caaaatgggc?ctccacattc??42480
atctgcccag?cacagaagga?atagttagct?ctcaatgagt?ctccaacttt?tttgacagaa??42540
attgctcact?gcttagaaat?tacaattctt?acagctcctt?acagcagggt?ttcagatttc??42600
acccagggct?gttacagtat?ttaaaaacac?acaagaaaaa?taagggttgt?aacccaaggt??42660
gatttttatt?tttttctttt?ccaagttttc?catattttct?acagcaagca?tatgttagtt??42720
ttataatcag?aaaaaaccta?taatctattt?tcactaagaa?tttaagttgc?tcttatgata??42780
gaaataatct?gtacatgatt?tctgaaggca?aattgaattt?tatccctggt?aatgcttttt??42840
gtagccctga?attaagtata?atcttcattt?acagagggca?aatttccttt?atcacagaat??42900
cagaaataaa?aatattttat?ccataattgt?ttaatgtagg?aaaactaact?ttaataaatt??42960
tatttcctaa?tgtaatagtc?tacatattac?ttctagtgtg?ttgaataaaa?acaaaaaaca??43020
aaaaacaaaa?aaaaacaagc?tttagggtta?gatagccttg?gcttaattcc?tggttgtgta??43080
atctaagcaa?atctcagttt?tctacactat?aattaaacat?tataatgagg?attataagaa??43140
tactttctct?cacagcttct?aatcaaatga?aactgcaaaa?ccacatggtt?agctaaaaag??43200
ctcccaggaa?gatttaaaca?attttgaaag?tgcataaggc?ttgaagaaag?tctgtgaaca??43260
atgccatgga?aattccaagt?tttttttttt?ttttttagat?ggagttttgc?ttgtcgccca??43320
ggctggagtg?caatggcagg?atcccggctc?gctgcaacct?ccgcctcctg?ggttcaagca??43380
attctcttac?ctcagcctcc?tgagtagctg?ggactacagg?cacccgccac?caagtctggc??43440
taattttttt?tttttttttt?ttttgtattt?tcagtagagg?cagggtttca?tcatgttggc??43500
caggctggtc?acgaactcct?gacctcagca?gatccgccca?cctcggcctc?ccaaagtgct??43560
gggattacag?gagtgagcca?cagcgcctgg?cccaaggata?tttttagaag?gagggtttct??43620
atgtgacttt?ttatatctct?agactatttt?acgttgattg?agtttgctct?tttttaaaac??43680
taaaaataac?aggacgtaat?aaagagatca?actacttcat?gtatactatg?aagaaatttt??43740
tgatatctaa?cagcagccaa?gtcttaatgt?atgagggatt?accaggatat?ggaaaaagcc??43800
agatacttat?gaaaattgag?tacctggccc?aaggtaagaa?tcacaggtga?gtgtcttgga??43860
atgattgttc?tgtgtgaacc?catagaatcc?tgatttattt?tgatgctcct?ctccttccta??43920
taacttgcct?tatgtaaatt?atctataacc?tacaattatt?ggatgccatg?acccttgtgc??43980
taaatagata?actaacaata?aacacataga?gctaagaaaa?agagaaactg?ggctgaccca??44040
tggatatcct?gatttaatgc?caggaagggc?ttggttattt?aaagtttcct?aagtaatccc??44100
aatattcaga?cagatcgaga?acaattggca?tagatgttga?gatcaaggct?agatttggtc??44160
tgcagaacaa?acacttaagt?ttatccagct?agctgacagt?gtagcaggac?cagctgcaga??44220
caaaacccct?cagacaccga?gatagtgaag?ggagtggctt?taatcagctg?ggagaatcgg??44280
caggctagcg?tctcaaaatc?cgagctcgtc?aaggtgctca?acttctgccc?ttttaagggc??44340
tcacaactct?aagggggtct?gcatgagagg?gtcgtgatcg?attgagtaag?ccagggggta??44400
cgtgacaggg?gctgtgagca?ctggtggtca?cagtgaaaca?gaacagaacg?agagatttca??44460
caatgtcctt?ccatacaatg?tgtggaatct?atagataaca?acagttgcta?ggtcaggggt??44520
cgaattttaa?ctaccaggct?taggtcaggc?aggcccaggc?ctggtttcgg?gtctggttct??44580
taggcgccgg?gctacctgcc?tttagtttcg?cttctctgtc?cttttctgag?tataaaacaa??44640
tataaaacaa?tatgagaggg?tctctctctt?ccctcatttc?ccccgtttga?gactctcact??44700
ttttattagt?gggagttctc?actcttattt?ttgccactta?tgccttcttg?tgcaatagat??44760
tgatagtgat?tcatatagta?cacttgtgtt?gaggcatttt?ggtgaactaa?ggtagcaatg??44820
aagcttttta?tcatttgaag?aagtacaggc?agcaagcaag?ggagcagtaa?gcaggtttct??44880
attactatta?taactcctat?ataagagttt?taaatcctcc?tagtgctggg?aaccaccttc??44940
taaacatggc?ttcagggtcg?aatccgtgct?acactcgtac?gggcatatgt?gccagttttg??45000
tcatgttttt?aactatgtct?ttaactacgt?ctttaactac?ttgcctttga?ttatctatgt??45060
gtagacagta?attagtaagg?ttaaattttt?atagacctct?ctttcagctg?ctagaagtag??45120
tcgagagcca?atctattttg?atagatagca?tttcttatct?gagtttcttg?ccgggccaga??45180
atagtcaagg?cttgactggt?tttattagtg?atgatttcta?aaacagcttg?caaccgtatg??45240
attcagttga?gcatgtaaat?gggggtctgg?tatacccatg?agccatcttg?tgtctaagtg??45300
gcaggcctat?agtattgtat?aattttttag?gtggtcattc?atcatctttt?taattatcta??45360
tggctatgtt?tcgcttttcg?cggaaagcat?agacagggaa?gcccaggagt?tcgcctattt??45420
gtatgggcag?taggaagaaa?gatggtttaa?tagtgccaat?aacacaacta?cctgtccact??45480
ggtcaggcag?cttagcgtag?gttctatgtc?cacgtatcca?gtatagccta?gtggggggct??45540
gtctagtccc?ggtggaattc?tgggtgggct?taaacggtct?gcaactttgg?aaatttactg??45600
aatggatttt?tatctgtgtg?gtttgaactc?caccatgtaa?ctgtttttgt?ggtaccatta??45660
tacagttttt?gtcctaggca?actaagtcat?cctacaggat?gagtgaattc?tttccttttt??45720
tcagctatgc?aatattgtct?aataattgag?acttttagaa?cctagaaatg?atcagggtga??45780
ttcttttggg?ccgggaattc?atcaggaact?gggtctgtag?gcactaattc?tcgggcttct??45840
tatgccattg?atctcttatt?acagtttctc?cacaaacgta?acatgaggtg?acatttagag??45900
actgggctac?atgctcggct?aattgcaaaa?acaaatttct?ggtttttcct?ggagtctctg??45960
gtactggcac?atttagttaa?tcatagaaag?tctgaaatac?tggttccgga?gagagtttac??46020
gaacctcctc?ttttactaag?gtatttactc?taggatctag?tcctttttta?tcgacgccca??46080
gagatacgtg?tacttctttt?tttctacctt?gggtttaagg?gatttgtaat?tactaatttc??46140
aaggggttgc?agcttccact?cgtacaggag?gggctgcctt?ctcctttttg?gagctaaaca?46200
gggtcttttt?catccttttt?ctaagtagcc?tagatgacac?aagaccagta?attacacaca?46260
tttgcacatg?agcttaattc?gtggcagata?tacttatttc?ctgctgtgta?actttttttt?46320
ttttcagttt?aaagaaccgc?atcttattct?atgccgattg?ctattgatag?tggcacaagc?46380
attaaatttt?agtgttacat?gcttggggat?ccctctttct?tctgtcttag?ctattacttt?46440
acttgtgtca?cctagaaaag?gaccagtcct?taatttattt?taaaaaactg?tgatcattgg?46500
aggcttaaaa?tgggtcataa?cacacatcag?gttggttatt?tcctaggcta?cataccttgg?46560
atagaatagc?attatacaaa?caagtttctt?ttagagtcct?cgtacactta?taataaccat?46620
gaaataatag?gactgtagca?atcttttgtc?ctacctcagt?gacttgatgt?atatactggg?46680
aacagttctc?agtctgagga?aggtcagttg?aagtccttac?tgtacaagtc?caaattttaa?46740
ggaaaatgag?tcccgtgatg?agttttctca?tgcttcggcc?gtgcgtggac?cagtcagctt?46800
ccgggtgtga?ctggagcagg?gctttttctg?agtcactttg?cagaggttgg?tgaagctgct?46860
cccatccacg?tacagctccc?agtttactga?tgtttaagga?tggttttgga?ggttgggccc?46920
actagaataa?actgagtcca?acacttctac?acagttatgt?ttaactgggc?tctctgatac?46980
caggagcaag?gtggcggggt?ttagggtgtt?gcaaacttca?atggttatgt?ggggattttc?47040
acagagcaag?ctttggtatc?tagttagtct?agcattcatt?agctaatgat?gtcctttggt?47100
actgattaaa?gtcaccacag?catggggggg?actttatgtt?taggttttgc?ctaagagtta?47160
gcttatctgc?ttcttgtgct?aacagggccg?ttgctgccag?ggcccttaga?tatgggggcc?47220
agcctttgga?aaccccatct?agttgttttg?agagataggc?cactggcctt?ggccagagcc?47280
ctacagtctg?ggttaaaact?ccaactgcca?tttttttttt?ttgaagataa?ccattctttt?47340
tttttttttt?ttaagtgaac?tttctttata?tctgtggact?agactgtcta?aggccacaag?47400
attagaagtt?actataatac?atgttacact?gttaactttt?agcaaacttt?acttttgttg?47460
aaaaccttgt?aagtttggga?tttcaattat?cctttgctat?gagtaagacc?ttgtttagtc?47520
taaattaact?tagaattggt?atagatggcc?cttttttttt?tttttttttt?ttggcacata?47580
gagtgtgcac?tttcgtcagg?tcaggtagcc?ccagggctgg?ggccgacctg?agtttttctt?47640
tcaactcatg?aaaagcttgt?tgctgttgtt?tgtaatagat?ataatttatc?taatttacat?47700
ttttattaac?atcactcact?aaaatattga?cttaaatttt?gtagctattt?gatttcaagc?47760
tttaaattga?tctggtattc?ctcgtgggac?tccaattgcg?tctaaatgga?cgtgagagtc?47820
gaaagaccta?taagggggct?tctctcgctt?tacgatgtct?tatttttcct?ccctcttgtt???47880
gatgaaatgc?cagggtgaaa?gggatagcca?actggactaa?agtataagtg?ccactccagt???47940
tattcggcag?agtgcccagt?aaaggtccac?cacaatacca?ccacacatcc?gcttggggat???48000
gaacaagggc?tgactgattg?ataagctctt?gaaaattctt?aagctcattg?catcacttca???48060
ggtctccaag?gaatcctaag?tttcctctct?gtggtgagag?acatgaagtg?aacttagtgt???48120
tgggagacgg?aggctggatg?gccctcgggg?gctgacccac?agggatagca?gagagagttt???48180
ggcatgactt?attactccag?gctgtagaat?cctggaaaag?agctaccatg?cagcccacgc???48240
ctggtggact?ggaggaccac?tttagtggaa?gggggacaat?gagggcctct?ggcctgccat???48300
gtgcacaagc?ataacaactg?cttttgttta?atgtgcagat?ggaatatttg?atccatttca???48360
accaggcatt?tgcatcttgg?tatgctgtct?taattgccaa?agtttgtttt?aagtctttaa???48420
cttctatgat?cctctagtaa?aatgaatgtt?tcctttagga?cctattttta?ttagttttta???48480
gaccaaagaa?agctaaacac?cattttatat?ttaataatac?ttcttgtatg?atttttatac???48540
cagataagct?aaattttacc?tttatattag?tgtgttatta?atgttaaact?taattttaat???48600
aaaacctcat?agacatattt?atccaatttt?tcatgtttga?ccataaggta?agtttttaca???48660
gactcttttt?aaccttttat?aatttttgtt?aaagagcagg?ttggtgcttc?aagaaaaacc???48720
tgttgcattt?ttactttaat?gtccagttca?cagaaaaact?ggatgatacc?tttttatctt???48780
tagctaatta?gtttacacac?agaatttttt?tttacaatta?acattttaaa?acttgcttaa???48840
actttcaaaa?caataatttt?tttaaccttt?taatgtaggt?aaaaatccac?attcttatgc???48900
ctccttctaa?tctttttacc?aaaagtatat?tttacttttc?ttatgcacct?tgcacataaa???48960
ctgtttcttc?aatagtactc?aggaggcctt?attactttca?aattatacaa?tattttttgc???49020
ataaattttt?tataacatcg?ttttctatga?ctttcgcaga?taattctttg?acatgtctca???49080
actttctgac?ttattacaaa?tatttctttc?tttaaacaac?agttaattta?tttcaagaca???49140
agaatttacc?atataacact?ctttttacat?aaattttgcc?ttcccacagc?tctttttttt???49200
tttttttcct?gttagcaaag?cagctgctgc?tacagattga?atgcatctgg?gccatccgtg???49260
ggttactggg?ttaaggattt?ttgataggaa?ggcctcagtg?ctttcgggat?acgcccttgt???49320
ttacactaac?aacaaagtgg?tattagagtg?ttacagggtt?acggagaata?cctttaatta???49380
tcaattttag?gttttaaatt?taccttggct?tttaaaggga?atagggtaca?ctattttttt???49440
cttaactact?tggatatttc?tctctatttt?tctttctctc?tttgactttc?tgtctctctc???49500
tctccctctc?tctctctttg?actttccttt?tgcctctgtt?tcttcctctc?tttctgcctc???49560
tcttaactac?tgtgggggcg?aagggggtct?aaaaccagct?gtaattgtct?acgtacagaa???49620
actggtctgt?gtgccttggc?ttacaggtta?ccttgtgcca?tacatttgaa?acaagggacc???49680
tgtctaggct?tccttctgat?ggccaaccca?cctctaatgt?tggccagtct?attttacaca???49740
aagttctaag?tttttctagt?gtcatagtaa?caccgtaatc?tcccttaaat?cctttcttga???49800
aatttttcaa?catagtttct?agtagggtgg?gcttatttgt?gcctgaccca?tgtttcttcg???49860
agacaaaaca?ccactctcac?accacatgca?caccacaaaa?caaagaacgg?gtaaaaaggg???49920
cacgcacaca?cttttgcagt?ttacactaaa?ccaaaatcaa?aaccaaaatc?agagtattca???49980
gaaatccaag?ccaggtcaaa?accaaaacca?aagtatcaag?caatctaagt?caagtcaaaa???50040
acaaaaacca?aagtgccgga?acaggcacac?cgtgggtgat?cagatcaggc?catgcttcca???50100
ctcaaatgga?gtgggaatgg?agtgggcaag?ttcccaagac?cagtcctgtc?aagtaattca???50160
aaccaagtca?aaaccaaaac?caagtgctga?taaaggcacg?ccgtgggtga?tcaggccatg???50220
cttccactca?aatggagtgg?gcaagttcca?aagactagtc?ttaccaagtt?ttagttgtcc???50280
ggactccaag?tgccaattcc?ttcccggtgt?tcagccactc?tgttgatcct?ccacgggggc???50340
ctgccacaca?ctgctctggc?gaggtgtccc?accggggcaa?atgcctaccc?aggagagctc???50400
tcaggatccg?cgtcactctg?gctggttgga?gtccccagca?gggatgttcc?acagggcagg???50460
ctaaagccgc?ctaaggagct?gcctcgacca?tctgttaatc?accttgcttc?ccggtcaggg???50520
aaccaagaaa?tgtagcagga?tgagccgcag?acaaaacccc?tcagacaccg?agatagtgaa???50580
gggagtggct?ttaatcagct?gggagaatcg?gcaggctagc?gtctcaaaat?ccgagctcgt???50640
ctgatgctca?acttctgtcc?cttttaaggg?ctcacaactc?taagggggtc?cgcatgagag???50700
ggtcgtgatc?gattgagtaa?gccagggggt?acgtgacagg?ggctgtgagc?accggtggtc???50760
acagtgaaac?agaacagaac?gagagatttc?acaatgtcct?tccatacaat?gcccttccat???50820
acaatgtctg?gaatctatag?ataacaacag?ttgctaggtc?aggggtcgaa?ttttaactac???50880
cgagcttagg?tcaggcaggc?ccaggcctgg?tttcgggtct?ggttcctagg?cgccgggcta???50940
tctgccttta?atttcacttt?tctttccttt?tctgagtata?aaacaatatg?agagggtctg???51000
tctcttccct?caacagggaa?tcactagttc?aaaccattta?gtcctaagac?tggagataga???51060
gaataagagg?tctttggatt?tttccctgga?agacagatct?aatatacttg?tctcatgttg???51120
tttatttatt?ttcatataag?gaatattatg?agggctatct?ttgggacaat?ccattctact???51180
tcctcatgga?agtagatagt?atggtattca?ataacagtgg?tgatgaccag?gacaataatg??51240
atggtgactc?atatcccttc?cccacctaac?ctaaacagtg?tgaggggaaa?atgcttgtta??51300
atcttataat?attcttagct?gtatctctat?cccacattaa?agttaggcct?gagaaaggcc??51360
agttttaaaa?tatctttatc?attgctgaag?ggataattca?caacagtcag?aagacatttg??51420
tttattcatg?tattcaatca?ttaattgaat?tcctactatg?ttcaggaact?actaagtgct??51480
gtattcacta?gccggggcct?ctgtaaaaaa?gtactacaaa?tggatggctt?acaacagaaa??51540
tttgtctcat?agttctcagg?ggtaggagtc?tgagatcaag?gcatcttttc?ttctctggac??51600
catgaggaag?aatctgtttc?atgcccacct?gctagcttct?ggtggttgct?ggccatcttt??51660
ggtgttccaa?agatggcttg?tagaagcgtc?accctaatct?ctgccttcat?gtcacatggc??51720
attctccctg?tgtgttgttt?gtgtccaaat?ttctcctttt?tataagggca?tcagttttat??51780
tggattagag?gcctacccta?ctctagcatg?atctcatctt?aactaattgt?atctgcaacg??51840
actctctttt?caaataaggt?cacactttga?ggccctagag?gctaagaatt?taacatatga??51900
attgtgggga?catgtgtcaa?caagtgccaa?agccctgaat?atcaataaag?tctgctctct??51960
gccctcaagg?agctctcaca?gaagaggagg?agagagataa?tgtgttagtc?gttttcacgc??52020
tgctataaag?aactacctga?gactgggtaa?tttataaaga?aaagaggttt?cattgactca??52080
cagttccaca?tggctaggga?ggcctcagga?aaattataat?catgacagaa?ggcaaagggg??52140
aagcaaggca?tgtcttacat?ggtggcagga?gagagcgagc?aagggaggaa?gtgccaaact??52200
tttaaaccat?caaatctcat?gagaactccc?tcactatcat?gagaacagca?tggggggaac??52260
cgccctcatg?atccaatcac?ttcccaacag?gtctctcccc?tgacactcgg?gggttgcaat??52320
acgggatgag?atttgggtga?ggacacagag?ccaaaccata?tcagatagca?ttaaaagttg??52380
aatatagtga?gggcaacgat?agagtcatgc?aatagagaat?tgtggaagtt?cagagaagaa??52440
agggtatgta?gtcaacctta?ggacattgat?gacagtttcc?aggaggctac?acctgagctg??52500
agacttgaga?tgaacctcaa?atgaggggca?atgagaagcc?atagcactct?gggctgagga??52560
gacagcataa?gcaaaggcat?ggagaggaga?aatagctctg?ggtgtgcagg?gaactctcac??52620
ctgcttgctg?ttggtgaagg?gtagattgct?aggcagagag?tggcaagaaa?ggatagaatg??52680
aggctttgga?aagtcttgtg?tgtcacataa?aggaggcctg?ggttcatgcc?gttaggcaat??52740
gggagctccc?agtcagaggg?tcatgacctg?gatgggggta?gtggcttgct?attgtggtag??52800
tatagggtgg?cagtaggact?agaaaggaga?gaattagcta?ggttaaatta?atcagggctt??52860
aggaacagga?gaagagggag?tatatcagaa?gcagcaataa?agaaccattg?cgagatagct??52920
tggaaaatct?ccatcattat?agctgaatat?gagaagacag?agctttcctt?caacctctat??52980
tattttcaaa?aatatatatt?taaaaactct?cttctgtttc?ttgattttct?cacaaacagg??53040
attattgcca?tttcattgaa?taagatcagc?ttccatcaaa?ctttctatac?catccagatg??53100
ttcatggcca?atgtcctagg?cctagacact?tgtaaacatt?ataaagaacg?acagaccaac??53160
cttcgaaata?aagtcatgac?actgttggat?gaaaagttct?actgtcttct?taatgacatt??53220
ttccatgttc?aggtaactag?ctagtattat?acttctgcac?aaatagccat?gggcaggcac??53280
agcaactcct?ctctggtgca?ttgtgactta?gcatctcttt?ggtctgtata?tctgcagtat??53340
ccagatggtg?agtaaatggc?tcccaatcct?ctctggatgt?gcatcaacat?tcttgacata??53400
ttagaggtat?cttgaaatat?catactcaag?aaaatccaaa?tggccatctg?ctgactaatt??53460
tttttcttac?ctttctatca?tagctatact?agctactctg?ggacacaaag?tcactctgtt??53520
cctacaagtg?atgccagtgc?agactgtgcc?ctgtcttttc?ctgaattatc?taacacaggg??53580
gtcctcaacc?cctggtacta?gttcatggcc?tgttagaaac?cagaccacac?agcaggaggc??53640
aaccagtggg?tgagcaagtg?aagcttcatc?tctatttata?gccactcccc?attgctcaca??53700
ttaccaccta?agctcctcct?cttgtcagat?cagcagcagc?attagattct?cataggagcc??53760
tgaaccctat?tgtgaactgt?gcatgcaagg?gacctaggtt?gcatgctcct?tatgagaatc??53820
taatgcctga?tgatctgtca?ctggcttcca?tcaccctcag?atgggaccat?ctagttgcaa??53880
ggaaacaagc?tcagggctcc?cactgattct?atctacatta?tggtgagttg?tataattatt??53940
tcattatata?ttacaatgta?ataatagaag?caaagtgcac?aataaatgta?atgcacctga??54000
atcatcctaa?aatcatcccc?tctgccgcag?ttcatgaaaa?aattgttttc?cacaaaacta??54060
gtccctggtg?ccaaaaaggt?tgggaccact?tatctaacac?atgaggattt?taagacacag??54120
aatagttaag?tgttttgccc?aaagttgcat?agccagtagt?tccctttgct?attttcccat??54180
actcaatatt?ctcataattc?tttgtacagt?tccctatttc?tcgggagatt?tccaggatga??54240
gcaccttgaa?aaagcaaaaa?caattggaaa?tattgtttat?gaagatcttg?aagctggtaa??54300
gagcatctgt?gggtcaagaa?gtagggggaa?gaaaactggg?caaatcacca?caaagccagg??54360
tggtttgagg?agttcagacc?acattggcaa?gaggcttttg?aaggatgtga?aggctttgtc??54420
ctaaagtgct?tcattctcct?ccatccttcc?aaacctcaag?caaaaggtct?gtttagaatt??54480
tagatgcctt?gaaaagagtc?ccttaacatt?actcctagga?gtctggcctc?tctcagcact??54540
cattttttca?tcctttgttg?agatataatg?taccaaagtg?gttacatatg?caggctctgt??54600
cgtcagacca?ctgaggtttg?aacccccagg?cctatcactt?gctacctgag?caacctcaag??54660
cagtgactta?ccctctctat?gtttctgctt?tatcatctat?caaatggagg?aaaataatag??54720
tacgtagctc?actgggatgt?aagtttaaat?gactagatta?tatgtagaaa?cacttagaac??54780
agtgtctctt?tcataagaaa?cactcaacaa?gtgttagctc?tctcccagta?atatcacgac??54840
tgtctgctat?atattgatca?ccaaatttat?atttcagtcc?ccacctctct?tataaacacc??54900
aaaaccatat?tcctaagagc?cttgtatata?ttccacttgg?atgtagtgac?tcacgctgag??54960
ttgagtgtct?aatgccaaat?tcattttttt?actatagtgc?cctttcttcc?tcatcctgat??55020
cctgatcctt?gatttcatta?gtagcaaatt?atgccattct?gtatcattta?aagttatcct??55080
tgccttcttt?tttgcccaca?ttcccgcatt?tactcactgc?caagtcctac?tatttttacc??55140
tcagtctctg?gaatctcctt?gtcctccctt?cctattgcca?tagttcaggc?tcttatcatt??55200
ttttcctgga?ctatttccat?agctttccaa?aaaactctgt?gcttcacacc?tctctgcttc??55260
aattcatcct?tcatataatt?ctcagagtat?atgcaaatca?caccaaccca?tactttatac??55320
tctcgaaata?agtcccagtg?gtaataagat?aaaagccaaa?agattttttt?taacctagag??55380
aaatggtgct?catctttcaa?tgtcacctct?ttggtgagaa?cttccccaga?tcactagaca??55440
tgactaattc?ttcttccacc?aggcttctgt?aaggctgtga?acacatttct?agttatacta??55500
tacactctat?actattatgg?catattgcca?ttcattactt?atatatctgt?ttctctctcc??55560
ctcaggaaat?cgtgagcctc?tttttttttt?tttttttttt?tttttgagac?agagtctcgc??55620
tctgtcgccc?aggctggagt?gcaatggtgc?ggtctcggct?cactgagacc?tccacctccc??55680
aggttcaagc?gattctcctg?cctcagcctc?ccgactagct?gggactacag?gcacgcacca??55740
ccacacctag?ctaatttttg?tatttttagt?agaaatgggg?tttcagtatg?ttggccaggc??55800
tgttctcaaa?ctcctgacct?tgtgatccgc?ccatctcagc?ctcccaaagt?gctgggatta??55860
caggtgtgag?ccaccacacc?tggcctgtga?gcttcttaag?aacagagagt?ctcttaacat??55920
ttccatatca?ctattgatga?gaaatgtgcc?tcataattgt?acataataaa?tgatcgatat??55980
aagttggtgg?cattgtatta?tatttataat?acagctttct?tcttttgtac?ttcaggtcat??56040
aggcaagaca?atatcagtag?tttctaagtg?tcagggctta?gactgtttgc?atcacaagta??56100
tttacaagaa?gctcctttaa?aaatatggat?ttgtgagttc?taactctaaa?gattaaaaaa??56160
gtaggatgtg?gattgggcct?aggaacctgt?ttagttgttt?gcttttgttt?taaaactttt??56220
cagttggtgc?tgaagcagaa?tcttgtttgg?aaactgctac?caaagctgtg?tttgattatg??56280
tactgacaag?tctttggacc?attaactatc?tgtgtgaccc?tgggcaagtt?acttaacttc??56340
tctgtgccca?aattttctca?gcaaatagat?tcaatagtac?cactttatat?ggatgttgtg??56400
aggattaagt?gagttaatta?tgtaaagagc?atcccgcagt?acttggaaca?tagtaagtat??56460
aatgtaagtg?ttggcttttt?ttcactttaa?aaagaaccca?atcctcattt?tagattagaa??56520
gaaaccaggc?caatgtttta?ttattgaatt?catgattttt?tgttcctgct?ttattctctt??56580
caatttatga?ataattcatt?aacaaggcta?tcccaagatt?aaaacttaaa?tttctatctg??56640
ccccatcttt?ttaaagatac?cagtcaaact?caaaacaatg?tagtgcttac?ctcctcatta??56700
attaaactgt?tctcagggct?agtcaaaggg?ctaagtattt?ggtgacagaa?cggggctgca??56760
ggagtagact?taggtatgtg?tgaacaaggc?aggttataac?actttataat?gactgtcaag??56820
cacaaagaga?aagaatgggt?taactcaatc?tcttctcaga?gggaaacaaa?aagcagccat??56880
tagcagtctg?gagcagtgag?aactggggag?ccggttttct?gcattgtgac?accttacaca??56940
gtggtaaggc?agagcctgct?acgtaagtgg?ttgacgctaa?aatgtaggct?ccgtattttg??57000
tttgagactg?tattcccagt?acctagaaca?gcacctgacc?ctgatagatg?cacaataaat??57060
gcttaatgag?tgaataaata?attcagacta?cttaggggag?ggtagtctat?atgagaaaag??57120
ggacctgtga?tctgtttttt?aagtgcaaca?cataccacat?ttcaagctag?aatagcatcg??57180
gctgccagca?gggcgaggac?tagttttgtt?cagcacctag?cccagggggt?gctcagtaag??57240
catgtgctga?atatatgctg?gttgaataaa?tgtcaagtag?atttccccag?gacaactgta??57300
ttgttcaata?gattaaaatg?actcataatt?aacaaaccag?ttatttttat?gtaatgggca??57360
cttcagttag?cttttgtggg?tacccctaaa?actccatcta?ttctccaaat?ttgcactatc??57420
tttacacaaa?gctttgacca?agtaagagtc?cattccagcc?agctctgtcc?aaatagccac??57480
aaattctaag?ttaatggaat?ataaatgaat?gcaaagttac?tggaaagaaa?agattgaact??57540
tagttctttc?gctgcatcat?aagcaaacca?ggaagctcaa?tggatacata?tgcataccca??57600
tacatgtgta?aaaaaacctg?acgtcctatg?gtgtttctct?ttctctttct?gcatcttgtc??57660
cagatagtga?aagaggaaag?gattattttt?atcattgatg?aggcccagtt?tgtggattcg??57720
acctcctgga?gatttatgga?gaagcttatc?cggactcttc?ctatcttcat?cattatgtcc??57780
ctgtgtccct?tcgttaacat?tccctgtgca?gctgccaggg?ccgtaataaa?gaacaggaac??57840
accacctaca?ttgtcattgg?tgcagtacag?cctaacgaca?tctccaacaa?gatctgtctt??57900
gacctcaatg?tgagctgcat?ctccaaagaa?ctggactcgt?aagtaacctc?tttctattct??57960
gaactctcga?catctgcata?cattccctcg?gtctagactt?catcagattt?cttagtatgt??58020
gtcttgatgt?gcctatttca?gtatctttcc?tggccccacc?ttttaaaaaa?tttttctttt??58080
ctttttttct?gttttctttt?gagacagggt?cttactctgt?cacccaggct?gaagtgtagt??58140
ggtgccatca?tggctcactg?cagccttgac?ctcctgggct?caagccatcc?tcctgcctca??58200
gctttctgag?taccagaact?acaggtgtgc?acctccggta?aattttttat?ttctgtagag??58260
atggggtctc?acagtgttgc?ccaggctgat?catgaactcc?tgggctcaag?caatcctccc??58320
atctcagcct?cccaaaatgc?tgggattaca?ggtgtgagcc?accatgcttg?gtctggtcca??58380
ccttttgaag?gagccattca?taatgcttgg?taggatggat?gttgctcacc?ttttccatgt??58440
tgcctccctg?ttacgccttc?ttaaactttg?cttagtgaaa?agctctattt?ccctttcatc??58500
atggggggta?tgggtatact?cactttaacc?tgcagtgact?aagagcattg?ttatgggcaa??58560
gtgacaggaa?aggcaaactg?gtaagcgtta?aagaccatga?cctgccacta?agcaaggtct??58620
tacctggctg?gcaatggtgt?ggtctggtat?tggtgttctc?tgtctatggc?agatgtggaa??58680
agctgactca?ctggtgagtg?ctctctgagc?ttttcagtga?ttcctctcct?ggggttttct??58740
ttgttttttg?tttgtttgtt?tgtttgtttg?ttttttgttt?tttagaccta?gtttcgctct??58800
cattgcccag?gctggagtgc?aatggcacga?tctcggctca?ccgcaacctc?cacctcccgg??58860
gttcaagcga?ttcttctgcc?tcagcctccc?gagtagctgg?gattgcaggc?atgccccact??58920
acgcccagct?aattttgtat?ttttagtaga?gatgaggttt?ctccatattg?gtcaggctgg??58980
tcttgaaatc?ctgagctcag?atgctccgcc?ctcctcggcc?tcccaaagtg?ctgggattac??59040
aggcgtgagc?caccgagcct?ggctctcctg?gcgtcctgac?agcagtcacc?ttaacaacat??59100
agagaatgtt?ttttctttag?ctggctgttt?acagcccatc?ttagtatctg?caatgaggtt??59160
gccctgcttc?tggaaggaag?atgtcttgaa?caaaggctca?tttaagataa?ctccaggcac??59220
caatttggca?ctcattcttt?ctgtcggtct?ctctctctct?ctccccctct?ctctgtttaa??59280
attatataga?acatgtatat?ctttccaaag?ccaaaaaggt?acatccttag?tcttgcttcc??59340
ctcccttatc?ctataggtaa?ccattttgat?tagtttttgg?cttatccttc?caatgtctgt??59400
tttaaaaact?ataaatcaag?tgtgtgcaca?cttattgtgt?acacacatga?gtgaaataaa??59460
aagaaaacaa?agcaatgcct?caaaactgaa?aacaaacaga?aacaaatgaa?gaatgacaag??59520
aaattatttt?caagtgattg?agaagactta?catatttttc?cttcctaaaa?gatgtatctt??59580
caatgtaaac?agattgcctt?gttttcacta?caggtacctg?ggggagggaa?gctgtgggat??59640
tccattttac?tgtgaagaat?tgcttaaaaa?cctggaacat?catgaggtac?tcgttttcca??59700
acaaacggag?tctgaggaaa?agacaaatag?gacctggaat?aacctgttca?gtaagtcctg??59760
cggtgatggt?tctttcttac?tctgttctgc?ctaacttaag?tcttcattca?gagaaggtag??59820
caaaaatgag?ctattccaca?ggctgcttcc?tgtagagtca?gaaggttctg?gggagccagg??59880
aattattgga?tccgatattc?cagattgtaa?gcgaacttaa?cattgcctgg?gactcactgg??59940
actcggctaa?agattgtcta?actatggccg?ggcgcggtgg?ctcacgccta?aatctcagca??60000
ctttcggagc?ccgaggcagg?cagatcactt?gaggtcagga?gttcaagacc?agcctggcca??60060
acatggtgaa?accccatctg?tactaaaaat?acaaaaatta?gccaggtgtg?gtggtgggtg??60120
cttgtaatcc?cagctactcg?ggaggctgag?gcaggagtat?ctcttgagcc?tgggaggtgg??60180
aggttgaagt?gagctgagat?tgcaccactg?cactccagcc?tgggcaacag?agtgagactc??60240
tgtctcaaaa?aaaaaaaaaa?aaaaaaaaaa?aagtaactat?agtagaaatg?aaagaacatt??60300
gacaaatctt?aaggcccaga?actgaagggc?cgctttgatg?ttatcttcaa?aaagcctttc??60360
cttttttgcc?agaggtaaaa?ttgctagtac?gaagtgagtt?atcaacaaag?atcccgtgct??60420
acacagatat?atacagggat?gaaatctgaa?gtgatggcat?gaaggaggcc?agttggaatt??60480
tttaggaaaa?taattttatt?gcagggaaaa?gggtgggggc?cagagattac?aagttggaaa??60540
gcagagaatt?aaggctagat?agagcaggct?ttaattggga?ctttttttgt?ttccactccc??60600
ttggtgtttc?tgagttgcta?gattcttaag?ctctaagtct?tgaacatgtg?aggcaaaaag??60660
aaagccctgc?catgggaccc?actgccacgt?ttttccttgg?gtcctaaggt?ccctagctgg??60720
tctgacttct?ttccaccttc?aatgtcatct?tctgtttgtt?ttacacataa?cgtctagggg??60780
ttttaactat?atttagcagg?aggaataggg?aaaaacatac?caactctctc?ttcctggaat??60840
tggaagcctc?ttcatttttt?tgtgactcaa?attaagtaat?acgatgattt?aacagctata??60900
agcacgacgt?gtattaatat?tactaaacct?agagggtcaa?aacgtattcc?tctgcgacta??60960
aatttaaaga?caagaatata?ggtgtgagat?cagtgtcatg?atgaggtgaa?tacggtgcaa??61020
taaaggactt?atggtgctgc?tgtctctatg?tagcaggata?gaaaatcacc?acctaaaggt??61080
gacaatgagg?gaaatttcat?aaaaaagatt?cctcttgctt?cctaaaaacc?cctgcctcct??61140
gggtgaatga?atgatgctca?gatgtcccta?tccatgtttc?agtctgtgct?gcatctgttg??61200
cctctcactt?cttgttcaat?agcatgacta?caggaccatg?tggcccccaa?gggcacatct??61260
gtaggagaaa?tgagacagat?ggttgtctga?gagaacaggg?caaagctcta?cctttttttt??61320
ttttaaggaa?caagaaacat?tagcttgctt?tttaaggaaa?gatcaatttt?ttttttcttt??61380
ctggatgatt?gtgatgaaaa?aatggagaag?actttctctg?gccaaattag?ttttaaagat??61440
gatagtggat?cattaaatag?ataatgactg?ctatgattat?tatttttaga?ctaaataatt??61500
ccattataat?aatattaaga?tgccaatgga?ttaaaggaaa?gcgatatgta?aatataaata??61560
ctgcagagta?aatactattt?ctaaatttta?tacatttgtt?tactttgttt?acttgttcaa??61620
taaatgttta?tgtagtatcc?gttatgagct?tttttttttg?agacagagtc?tcactctgtc??61680
gcccaggctg?gggtgcagtg?gaacgatctc?ggctcactgc?aatctccgtc?tcctgcgctc??61740
aagcagttct?cctgcctcag?cctcccatgt?agcaaggatt?acaggcatgc?accactaccg??61800
cccagctaat?tttcatattt?ttagtagaga?cagggttttg?ccatgttggc?caggctggtc??61860
ttgaactcct?gacctcaagt?gatctgcccg?cctcgggctc?ccaaaatgct?gggtttacag??61920
gtgtgagcca?ctgcacctgg?ccctgttatg?agctttttaa?aacacaatca?ggtgtcttct??61980
ctatttaaaa?cccttcagtg?tcttttgtgt?cttaatttta?aaaaactgaa?attaaggaga??62040
gattctggtt?acataatatt?gtgaatgcac?tacaggccgc?tgaattgtat?actttaaaat??62100
aattaattgc?atgttaggtg?aatttcactt?caattaaaaa?aataaatatg?atacataatc??62160
ctggactgga?tcctatactg?gaagaaaaga?gaatgttaaa?ggatattatt?tgatcaattc??62220
acaaaattgg?gatatggaca?gtagactaaa?gtattgtatc?aatgttaaat?ttcttttttt??62280
ttttttttga?gacactctgt?cgcccaggct?ggagtgcagt?ggcacgatct?tggctcactg??62340
cagcctccgc?ctcctgggtt?caagcaattc?tctgcctcag?cctcccgagt?atctgggatt??62400
acaggcaact?gccaccatgc?ctgactaatt?ttttttgcat?ttttagtaga?gacggggttt??62460
caccaccttg?gccaggctgg?tcttgaactc?ctgaacttgt?gatccaccca?cctcggcctc??62520
ccaaaatgct?gggattacag?gcgtgagcca?ctgtgcccga?ccaatgttaa?gtttcttgaa??62580
ggtgataact?atattctagt?tatatgagag?agtgttggcc?aggtgcagtg?gcccacacct??62640
ataatcccag?tactttggga?gtctgaggcg?ggcggattgc?ttgagcccag?gagtttgaga??62700
ccttcctggg?caacatgaca?aaaccccatc?tctactaaaa?atacaaaaat?tagccgggtg??62760
tggtgtcgca?cgcctgtagt?cccagctacc?tgggaggctg?aggtgggagg?attgcttgag??62820
ccagggaggt?tgaggctgca?gcaagctatg?atcacaactc?tccactccag?cctgggcaac??62880
aggagtgaga?ccctgtctca?aaaaaacaaa?acaaacaaac?aaacaaaaga?gtgtcaatat??62940
ttttagaaaa?tacagagtaa?agtatttggg?agtatagggt?gtgatgtatg?tgacttatat??63000
tcaaatgctt?cagaaaaata?tgtacacata?gaaggaacct?aggatatagt?aaatagggca??63060
aaggctgaca?acaggcgaac?ctgagtaggg?agtacattct?gtctatcacc?cttttatttc??63120
tttcacataa?ttgaattacg?agattatcct?tttaatgtat?ttatctattg?tttaatgttt??63180
gtttcccact?agaatgtgag?cttcatgagg?catggagttt?tgtgctctcc?tgaatcccca??63240
atcctaggaa?aattcctagc?acctagaggc?aatcagttaa?tactggttga?gtgatggaaa??63300
gaatggttgt?ctcaatgcta?ggtcctggaa?ggggaaataa?gcataaaata?gcatggacca??63360
cgtcatatcc?ttgagcccca?ctctcctact?cccaacacac?acacacacac?acacacacac??63420
acacacacac?acacacacgg?cccccttttt?ggtatgctat?cctcccttgg?ctttcctgac??63480
cccacactcc?tcctgttccc?ctctctgacc?agtcctcaga?taatccttgg?ctctctacct??63540
gggtctactc?ctcctgggac?attcttcaag?ttctatcctt?aaccctttcc?tcttgctagc??63600
ttgccagaat?tggaaacaac?tctctcccca?gttgttttca?tttactcatc?tatttctcag??63660
ccttcgtgtg?tgtcgaaccc?taacctcacc?cttaattcca?cacccatatt?tccaattgcc??63720
cattgaacta?ttccacagat?tcccttaaac?ttaataaatc?taaaacttca?tgcattatcc??63780
tcccgctcaa?ccacccctcc?ttctgtactt?cgtgtctctg?tcacttctat?cactgtcttg??63840
cttaggcccc?atttcctcca?tatctttagt?atttgctttc?tccttgctga?accacttgcc??63900
tggttctatc?catcctcact?tcttgacatt?ccattgttat?agctccttac?atagtcttcc??63960
ctgtcctagt?ctctcgcctt?ttccatatgc?tgcttccagt?ggtaccttcc?taaatacgac??64020
tagttggatt?actactatct?cctcttcaga?aatctgtgac?ctttccctct?tgtctataaa??64080
gtccagtctt?catattatgg?tgtttaatgc?cctccatgct?ctgctcccaa?actagctctc??64140
caaacacgtc?tcccacatag?cacctgagca?ctccaggccc?tgcactttag?tcacgctggg??64200
ccgctccatt?cccctaactc?gctaagtact?ctgaggttcc?tgtgccttcg?cgttggcctc??64260
tcctccactt?gccgcttaga?atatctcttc?atccttcaag?gatcaaagta?cttcctcccc??64320
tatcaagcct?ttctgaatcc?accaagtctg?atttaattgt?tattttctgt?tcccacaaca??64380
tgttactctt?tgctctttag?ctcttaagtc?acccatcctg?atgttataat?tagttactta??64440
tgtatctgtc?tccacagatt?tttaagcctc?ttgagggctg?gaagcatgtg?ttattcacat??64500
tgatagcctt?cactggatat?gatgcacaga?aagtccttaa?taaatatgtc?ctgtattgat??64560
gtgaactctg?gtgcttactg?tatgtgccca?atcacatggc?actcatctac?tgcctggcag??64620
tccagctctt?agtgtacatg?acttagagct?ccaggaaata?aggaacttgg?ttttattcac??64680
cttcctattt?ccacctcacc?tagcacagtc?ttgccgctac?caaggactac?atgaatggct??64740
gaagggatag?aaaaataatg?cattttggag?tactaggaaa?ccaaattact?aggcacattt??64800
actattcaaa?cttcaccatt?taaaatatct?ctgatagtag?ctatgtccta?attagagtac??64860
agtgcctcac?agaatgtgtt?tgtaactgag?tgtgggtatg?taaatgtata?catacaaata??64920
tatgtttatg?tatatatata?ataatacatt?ctgatataca?ttatgtatat?acataataca??64980
tatataatac?attctgataa?tctgactgtg?aatcaaacgt?ttgtaaagcc?ttatatccta??65040
tggaagacat?caatagtgcc?aattcttttg?gttgggcagg?gttggcagag?ggagacaaaa??65100
catttttgag?tacatctaga?ttttcatgaa?tcagttttac?ttagaataag?gtttccagcg??65160
gcctggtgca?gtgtggctca?tacctgtaat?cccagcactt?tgggaggccg?aggcaggcag??65220
atcacttgag?gtcaggagtt?tgagaacagc?ctggccaaca?tggtgaaacc?tcatctctac??65280
agaaattagc?caggcatggt?agtgggcggc?tgtaatccca?gctacttggg?aggctgaggc??65340
aggaatcgct?tgaacctggg?aggcggaggt?tgcagtgagc?aaagatcacg?ccactgcact??65400
ccagcctggg?cgacagtgag?agactccacc?tcaaaaaaac?aaaaaacaaa?acaaaacaaa??65460
acaaaaaaaa?ggtttccaga?atatttggtg?agccaatata?catctctgcc?cagtcttcct??65520
catatgagat?ccatctcaaa?gttcattgga?aaatcagacc?ttataagaca?ggataatgac??65580
tcaacttttc?ttccctttta?tacccctgta?gagtattcca?ttaagctaac?agagaagtta??65640
aacatggtta?ctctccatag?tgataaggaa?agtgaagaag?tctgtcacct?cacaagtggt??65700
gtcagactga?aaaacctgtc?acctccaacg?tcattaaaag?gtaagaaaat?ctggccgggc??65760
gcagtggctc?acgcctgtaa?tcccagcact?ttgggaggcc?gaggcgggcg?gatcacaagg??65820
tcaggagttt?gagaccagcc?tggccaatat?ggtgaaaccc?cgtatctact?aaaaatacaa??65880
aaaaattagc?caggcacaca?cctgtaatcc?cagctactcg?ggaagctgag?gcaggagaat??65940
tgcttgaacc?tgggaggcgg?aggttgcagt?gagccactgc?actccagcct?gggtgacaga??66000
gtgagactcc?atctcaaaaa?aaaaaagaaa?agaaaatctg?acctggtatt?tattttctag??66060
tccctaaact?ccactttggc?tttctctagg?atgtctgttt?ttaaaaggaa?aaagaaaaac??66120
agcaacattg?gttgtttgtc?tgtttgctct?gtactgcctg?aagcagtgag?aaggctcagg??66180
gtaggcttgg?ctttgctcct?aagagccatc?tttccccctg?tgtatattct?gggatctgca??66240
taaaagaatg?aaatattgta?cattttcaat?taaacagaaa?ccaaataatg?agggagaaaa??66300
tctaatactg?agatacttcc?tgtcatccac?ttttatgaga?aagaaatgac?aaacgagttt??66360
atatgaaaga?catattattg?gccaggcaca?gtggcttact?cctgtaatcc?cagcattttg??66420
ggaggccaag?tcgggtggat?cacttgaggt?cagaagttct?agagaccagc?ctgaccaaca??66480
tggagaaacc?ccgtctctac?taaaaataca?aaaaaaaatt?agccgggcat?ggtggcgcat??66540
gcatgtaatc?ccagctactg?aggagactga?ggcaggagaa?ttgcttgaac?ccaggaggcg??66600
gaggttgcag?tgagccgaga?tcacgccatt?gcactccagc?ctgggcaaca?agagaaaaac??66660
tctgtctcaa?aaaagaaaga?aagaaagaaa?gaaagatgta?ttattattct?tttaaagaaa??66720
aatgactttc?aaggaatgtt?ttagtatgaa?ctcagctcca?attcatgcca?tccataagca??66780
actttcaatg?tttagaaagg?tggcctaggg?acatctcaag?gtcctcagtc?ttcaaaagag??66840
tgccatttat?gtttcgttag?ctgtgtctac?taatgtgaga?aggcagtagc?tcacacctgt??66900
aatcccagca?ctttgggagg?ccgaggcagg?tggatcacct?gaggtcagga?gttcgagacc??66960
agcctggtca?acatggtgaa?atcccatctc?tcctacaaac?acaaaaaatt?agccgggcat??67020
ggtggtgggt?gcctataatc?ccagctactc?aagaggctga?ggcaggagaa?tctcttgaac??67080
ccaggaggcg?gaggttgcag?tgagccgaga?tcagccattg?cactccagct?tgggcaacaa??67140
gagtgagact?ccatctcaaa?aaaaaaaaaa?gaggatggac?tagcttagtt?tctactgtgt??67200
tttttgggca?agttgagaaa?ttctaatttt?gtccctaaca?gaaggacatc?ctggtcaaaa??67260
tgtccagaaa?gtcacatgag?ctaccgatat?tcaagcttag?atgaaaagtt?gggataggag??67320
ctgtgaactc?tctgacactt?ggtcatgaca?cagagatgat?aatgtatgtc?atgagaatac??67380
ataaatttct?agggcagata?gagagaaacc?aggagtttct?aggagaaagg?ggaggcagag??67440
aagaagatac?aaaaggacca?gctgaggaag?tcaacaaagc?acaggaatgg?cagggcctgc??67500
tccttctgac?aatagtgatt?acaatgtcct?ctcctctcct?cacacacact?tgtcacactt??67560
tagcacaaaa?tcagaacacc?atgaaataga?tcttaatttt?gtcaggtcat?tgtgctgtgt??67620
gtctttctag?gccataagcc?tgcatcttta?gtactcccag?cacaagtgct?atccacaaat??67680
taggtactaa?acaaatactt?cttttgactt?agcttggctg?agtttcttgc?aacaagaact??67740
gtagagcagg?atggttgtcc?acctgctcta?tattaaatac?agcatattag?ataaagataa??67800
ataactagtt?ttctactgtg?tggccttcta?cctgcagaaa?tctctctgat?ccagctggat??67860
agcatgagac?tttcccacca?aatgctggtg?agatgtgctg?ccatcattgg?cctgaccttc??67920
accactgagt?tgttgtttga?gattctcccc?tgttggaata?tgaagatgat?gatcaagacc??67980
ctggcaaccc?tagtggaatc?taacattttt?tattgtttcc?ggaatggcaa?ggagcttcaa??68040
aaggccctga?aacagaatga?tccctcattt?gaggtgcact?atcgttcctt?gtctctgaag??68100
cccagtgaag?ggatgggtga?gtagcacctg?gagtgaccca?atttcctctt?aaggacccat??68160
ctagatcaaa?gaattgacct?atgttaggta?gaaggggctg?atctgttgcc?cactgcctgg??68220
ctgaaaaacc?ctttttgctc?tctccagatc?acggtgaaga?ggaacagctt?cgtgaactgg??68280
agaatgaggt?gatcgagtgc?cacaggattc?gattctgtaa?ccctatgatg?cagaaaacag??68340
cctacgagct?gtggctcaag?gaccagagaa?aagccatgca?cttgaaatgt?gcccgctttt??68400
tagaagaaga?tgcccacaga?tgtgaccact?gccgaggcag?ggacttcatt?ccctatcatc??68460
acttcacagt?gaatattcgg?ctcaacgctt?tagacatgga?tgccattaaa?aagatggcta??68520
tgtctcatgg?atttaaaagt?aacctacttc?attttaaaat?tatcctaact?gttcttggga??68580
aatctagaga?ctaagatcta?gaaggagtgg?gtgtggatct?tgagggcttc?aagtctcata??68640
agcggcttgg?gcacaaagaa?tgatgagact?tcagcagcct?aggccaatgg?ggaagagaaa??68700
agtaagggaa?tgtacctgta?ttgagtctag?cgaaccaatc?tcactataac?tgtcagggag??68760
ggtttgggga?taggggctct?ggcaaaatgg?gatgtgacca?gaactcaaac?taaaatatcc??68820
cacttaattc?acaccaaagg?atggaatcca?aaggggggta?caatctgaca?tgatgacatg??68880
gtgtttcttg?gcagataaga?atattattgc?tttgttggtc?tagtttgaaa?caggttccag??68940
tgggtaaaga?acatgactga?gagagaatta?gccagggcta?agcaggtcag?ggctccagaa??69000
aacagggctt?ggtttcaggg?caagaattca?agaccatcgg?agaagcaaaa?gttaaaaagt??69060
tacaagccaa?taataccaac?cagccatgtg?atctgagaaa?acatagcaga?ggattcaggg??69120
ggtgtaagga?cccaaagact?cagtcactat?gggcatgatg?ggtgtcagac?acagagcaac??69180
accaccaatt?ctagccccca?ttcatggtgg?ccagggagct?cctaatgggc?tgcctactct??69240
agtcagagga?ccttggtgat?tatggctaaa?tctggttggg?aaatcagagg?ctacaagtag??69300
aggactccta?tattataagg?atattaaaaa?tcaggaagaa?atgtatctaa?actgcctagt??69360
acatagcagg?tgcaaaataa?actttttttt?ctcattcgtt?ctccatttca?tgtgccttct??69420
cagtggatcc?tcatattaac?cctttaaggt?tgatgagggt?tgttttcatt?gtatagattt??69480
tttaaattgt?ggttctggaa?gcttaagtaa?cttacccaat?accacagaat?gagtgacagg??69540
ctttattcaa?tctgccatca?gtctaattcc?taagttcatc?ctctgctcat?tatacctgag??69600
ctcccccaaa?tgtggggttg?gattttaggt?aatacttgcc?agaagatagg?aagttcgtag??69660
acacagcatg?aagtagaaat?caagagaatg?agaaagttgc?agctttgcac?agtgggacga??69720
gcatgttgtt?gaaactgcac?taacactagt?ccatctccct?ttttggaaaa?caggaatcag??69780
gctgtaggtt?cagagcctta?ggatctggac?catgaagatt?tttagtcctc?tgagagcttg??69840
agtacaaaga?ggataagact?tcagcaatag?tctcatctgc?actgggcagg?gaagatgtca??69900
ggggaatgta?cacctacctg?agtctagttc?tattactagc?atttattaaa?ttctctcttg??69960
tttgttatat?ttttacaaaa?ttggtaatat?tattatcaca?aaagtggtat?gtgtgtaata??70020
ttatgttgaa?attgaaattt?gtgccagagc?accaagatac?aactaatgct?gcaattcaaa??70080
ctgaggcagt?ggatatacag?aattacaaaa?gaaatagctg?agaatcaatt?ataatcttgg??70140
atccttcgcc?cagacctaag?acatagaaat?gaggaagagg?atgtagaggg?tcaggatttg??70200
tgaagagatc?tctttggtga?gaactgatga?ggtgctgtgt?gccctcctca?agtgggttgt??70260
ttacttcatc?acctcaagcc?tggtgaggtg?tcttccttag?aatcagagga?catagaacac??70320
tggggcctgc?ctcatgccta?agaaggctga?agtggcctgt?ggctgcattg?ggatcaagct??70380
gccatcccag?actgtgggaa?aggatgtgtg?agggtttctc?atggatcaga?taaaacccac??70440
ctgggagaaa?cagccagtct?ggaaccattt?taagttcttc?ccagggtgcc?cttgggaggg??70500
taacaagacc?cttgggtgtg?gactgctaga?atgagacagg?gataaggggg?acagactgga??70560
gcaccgagaa?gatgcgctgc?ctgaattaag?gaagctttag?tgaaggatcc?cacacagggc??70620
cctattcaaa?gaaccaatga?aagtatcagt?aggagatgaa?atgatggaaa?gagatgaggg??70680
aaaggggaaa?gaagaatatt?tgactgtgcg?gggtcagtga?gtcatacata?tacacacaca??70740
catacacatg?tacacacaca?tacatataca?tagatgcatt?ttttggtaga?ttgatgtttt??70800
attttggggg?ataaaataag?ctaaaataca?ctgacagcta?gaatataggt?cagtttgagc??70860
agctggcctt?gagcaggttg?actagtgtca?tcaaagcaaa?caatttcagt?tatttgcaga??70920
ttttccaatc?aactggcagt?tcagctctgg?aacatatatg?accaaatgtc?tctgaataat??70980
gtctgctggt?atcccttcca?tcagcacctc?cacctgagtg?aggccacagc?tctactattt??71040
ctcttatcag?aatttttcac?ctgttcagaa?ggctatcgac?tcgacaaact?ttagagactt??71100
tgtaaattcc?ctaaatgtcg?tatcacaaaa?cagtaatccc?atggccgacc?gtcccacaca??71160
ccttcagtaa?ttccagtcag?gggcaaacat?ttttaattta?gctgttcttt?ctagtcatta??71220
cctccatata?ctaaatggta?tattaacatt?gcttttactg?atttttaaga?aaatcaaatt??71280
ctgacatctg?ttttctggct?atggcagatg?aggatttaac?tctgttacac?cactcctcgg??71340
cccctctccc?ctatattgtc?atataactgg?cattagataa?gccaatgaag?tgtttacatt??71400
attaagacta?tgtaaatgtt?gtccattaca?aaccaagtaa?tatactgtga?atagatttct??71460
taacaaatgt?ttattttccc?tagggttact?aggaaacgtt?tttttttttg?cagtgtcttc??71520
cttaaaatat?cctgctttaa?tctatcctag?acagatagat?actctgtcta?tcctttatcc??71580
ctgaacctcc?caaagtgtgg?agtataacct?ttaggcaata?ctggtcaagg?acataattgg??71640
gaccaagtgt?ggtggctcac?gcttgtaatc?ccagcacttt?gggaagctga?ggtggaagga??71700
tcacttgaag?ccaggttcaa?gccagggctg?gttcaagacc?agcctggaca?acaaactgag??71760
actctgtctc?tacaaaaaac?taaaaataag?aaaattagcc?aggtatgatg?gcacacatct??71820
atagtcccag?tttctcagga?agttgaggtg?ggaggatctc?ttgagcccag?gagttcaagg??71880
atgcagtgag?ccgtgatcat?ggccactgct?ctccccaaaa?ggggaaaaaa?aagacataat??71940
tggaggagat?tcagggctac?tgcattatgt?gtgaatcaga?tagggaggaa?gctggtagct??72000
ggtccctttc?aattctcttt?tgatcctcat?gtccttctta?agaactgtta?ttttctaagt??72060
cttgattcat?tccaacggtt?taccctcctg?ggggctgtcc?ttcagcttct?tccacctatt??72120
tcatcagtga?ctactcttct?cactccttta?tcttctacag?atatgttgaa?ctttcattca??72180
gcatttcatt?tactcattcc?acaattattt?atttatgtgc?caggcattgc?ttactgctct??72240
aggcatctga?aatgcatcgg?tgaacaaaac?agcattctgt?tggagaaaag?tagacagtgg??72300
agaacaaaaa?cataataaag?aagtaaatat?ctgggtgcag?tgactcatgc?ctataatccc??72360
agtggctttg?gaggcttgag?gccaagggtt?caagaccagc?ctgggcagga?tagcaagacc??72420
ccatctctta?aaaaaagaat?tagccaggtg?cgatggcttg?tgcctgtagt?cccagctact??72480
caagagtatt?gcttgagccc?gaaagtttga?gactgcagta?agccatgttc?accctactat??72540
actccagcct?gggtgacaaa?gcaagacccc?aactcttaaa?aaaaaaaaaa?aaaaaaaagg??72600
aaagcatata?gtataagcga?taaatcccat?ggggaaaaac?agaaaagaat?gttgggtagg??72660
aggagcgcag?agccatttgg?gtgacttcac?tgcaaagcaa?gattcatgta?aagacagagg??72720
aagtgaggga?ttttgctgtg?tgagtggctg?gggaagactg?ttctaggcag?aggggtagag??72780
aatgcagtga?ccctaagaca?ggagcgtggc?ccttccattc?tatacatgtt?gaatttatac??72840
ttttagagat?cattttattc?ttgccaggca?cagtggctca?cctgtaatcc?cagcactttg??72900
ggaggctgag?acaggtggat?tgcttgagct?caagagttca?agacaaacca?gagaagcatg??72960
atgaactctc?cctctacaaa?aaatacaaaa?aaattagctg?ggtgtggtgg?caggtgcctg??73020
tagccccagc?tactcaggag?gctgaggtgg?gaagatcatt?tgagccaggg?aggttgaggc??73080
tgcagtgagc?tatgatggcg?ccactgcact?ccagcctgag?cgacagaaca?aggccctgtc??73140
tcaaaaaaaa?aaaaaaaaaa?tcattttatt?ctcatttagt?taggtaaaat?gtcctgaacc??73200
tggggagaca?gaagataaac?ccaagaggta?gtctgacatc?ttgaacctaa?agtcttagtt??73260
ttagttcttt?gaaaccataa?ggtgggcagg?tgatatcttt?gcttttctct?tttcatttga??73320
gaacctatag?gcatttgtat?gtttttttct?tttgattttt?acagattctc?cttgtagtag??73380
gaaactctta?atataatatc?tcctttgtaa?atgaaaaaaa?tgagaatcaa?aaataatatg??73440
attctggttg?ggcacggttg?ctcatgcctg?taattgcagc?actttgtgag?gccgaggcag??73500
gcagatcaca?aggtcaggag?attgagacca?tcctagctaa?cacagtgaaa?ccccatctcc??73560
actaaaaata?caaaaaatta?gccaggcatg?gtgggacacg?cctatagtcc?cagctacttg??73620
ggaggctgag?gcaggagaat?cgcttgaatc?caggaggcag?aggttgcagt?gagctaagat??73680
tgcaccactg?cgctccagcc?taggcaacag?agtgaaactc?catccaaaaa?aaatagtaat??73740
aataatatga?ttcacccaag?caataaatga?cataatgaca?aagagcatac?ctcatatgcc??73800
ctgattctat?ttgctttatc?tatccaatct?ttgcatccca?ttctatcacc?attaccattt??73860
tttttttttg?agacagggtc?ttgctctgtt?gcccaggctg?gaatgtagtg?gcatgatctg??73920
ggcttagtgc?agcctcaaac?ttccaggctc?aagccatcct?cccacctcag?actcccaagt??73980
aggtgggact?acaggcacat?gccaccatgt?gctgctaatt?tttttttctt?ttcttttttt??74040
tttttttata?gacaggtctt?gccatgttgc?ccaagctagt?ctcaaactcc?tggactcaaa??74100
cgatcctccc?acctcagcct?cccaaagtgt?tgggattata?gggatgagcc?actgtgcctg??74160
gccaccatta?caactttaaa?cataaaaaat?acatagaatg?ttgaagaagg?aatagcattt??74220
tcattttact?gattgattta?ttttcaacaa?acgtgcgttt?atgcaacaaa?catttattaa??74280
gcgtctacca?tgtgccagga?agtgacctag?atattcggac?catagtagtg?aaaaatggta??74340
gacatttatt?atcaattttt?attttattat?taagatagac?atgtctcttc?ttataaattt??74400
gaattttaat?ggcaactgac?agacaatgaa?cagattaagt?aataaaatct?tcaaggggcc??74460
ttgtagactt?tgataaatag?tctaaatttc?agtctaagtg?aattggaaca?cattggaaat??74520
atatcaatta?gaatgagtat?tggctgcata?taataaggac?ctagctagtg?tggcttaaat??74580
ttatttatta?ttaaatgtat?tgtatttatg?tatttctcat?gtaaaaggct?tgcctcatca??74640
ctgggactag?tatggaggct?tcatgatcat?cagggtcctt?ggtccaaaac?agctgctgag??74700
gctccagcca?gcatgtttaa?tgccagaagg?agaaaagaag?ccaaaacatg?aaaggatatc??74760
ccctcccttt?taaaggatct?tctaaaagtc?ctacccagta?tttcctctta?catcccattg??74820
atcagaacct?actcacatga?ctatatccag?ttgcaaggga?agctgaagaa?tgtcgctgtc??74880
tattactaat?gagaaaaggg?acaatggaga?ttgagttggg?aaaccggcag?ttcctgccac??74940
agagatctga?atcatgcttt?ttaaatggta?ctgccttctc?tacagaaaga?gattgaaaag??75000
gataggaata?gaagggagat?tagttttttg?cagttgtcca?ggtaaaattt?tggtaatgga??75060
ctgaggtggt?gctgtagtga?agatggacag?aagacgatga?attcagatat?gtttttgggt??75120
atggtcaacg?ggactttctg?atggactgaa?tagggaaggg?ggtaagaaaa?agaaaataat??75180
caaggatctt?gcgcaggttt?ttgtcttgag?aaaatggata?tatgacagtg?atgcttacta??75240
tgttaggaaa?agttgtaagt?gggtataagt?ttctggagga?gagattcgag?agtttctgtt??75300
tgaatcatgt?taattttgaa?atgcctatta?cacattcaaa?tggcagttgc?caaggtggta??75360
tttgaatata?tgggtctgta?gttaaagtag?atgtcgaggc?ttagatatat?aaaatggaaa??75420
tccattagca?tatgaatgta?attaaaagtc?atgggcagat?gaaactgcct?agggagaaat??75480
tgtgaaagga?gaacggagcc?caggaccaaa?ctgaggttta?ccaacattta?gaatgttggt??75540
agacgaatag?tagccaatta?agtaggcaac?caattccctt?ataacacaca?aaacaatgtg??75600
tgctaaaaga?atcagtgaaa?agggagagtg?gtcacttgta?ttaaatgctg?ctgagaggta??75660
atcaagtgca?gacaaagatg?tagcctttgg?atgtggcaac?atggtggcca?caggtaactt??75720
taacaacagc?agttttagag?aagtaggggg?acagggtcat?aattcaatat?attcagctgc??75780
tagtcactaa?ggaatcaata?aatagtaatc?taggagaaga?ggtggccaaa?ttgatctctg??75840
tgcagtacaa?taaggactat?gatacaggtc?tgcacagggt?tgacgggcac?acaggagttg??75900
gggtacttat?ctatggaggc?aagagcacag?agggctttca?gaagaaggtg?gtaacttctt??75960
agatgttcaa?actgcatcta?taagatgtat?ggagtaatgc?attagcctgg?gagccagaaa??76020
acctaagttc?tagtcctgcc?tccaccacta?acagatgtat?gacctgagac?aagttcattc??76080
ccctctctgg?gattctttct?tctgcctgaa?gggagaaatg?gctggactag?acaagcctca??76140
tttgttttct?gttttaagat?cattatggaa?ttttctaacc?tgttcaagtc?tgcttagact??76200
gaggttttta?atttaagatt?ctctgccctt?cagttaacct?tttggggtat?ttcatttaat??76260
tatctatatt?tctccactgg?aaattgatgt?cactttcttc?aggtttaatt?catagttttt??76320
attgcagaat?aaatgagtta?ggataatgtt?attagctatc?acaaacccca?gcatttctgt??76380
ggattaacac?aagagagtga?ttatttcccc?cttatgaaat?aatccaatgc?aagtgttgac??76440
caatggcttt?gcatgcagtt?agcaagggac?ccaggctcct?cccaacttgt?gggtttgcta??76500
tccttcaggt?tcttagaatt?acttgctttc?ttgtggaaag?agaaggcaga?gaagacacat??76560
aaccatctta?gcctagaggt?gacatatatt?acttctgatc?taattctatt?gtgagaactc??76620
atcacgtggc?ttcacctaag?atacaatggg?gactaggcaa?tgtggtttct?ggctgggcag??76680
caacaactcc?gaaaagggaa?caagagtctt?gggtagacag?cagatatctc?cactgcagag??76740
aacatttcaa?tgacccatac?aactcatttg?tttattttct?agctgaagaa?aagcttatct??76800
tgtccaactc?agagattcct?gagacatctg?cattttttcc?tgaaaatcgc?aggtagaggc??76860
atatatcatt?gtttaggaag?tagagcataa?ataattgtca?ttaaattcag?aacactatta??76920
gaatcatttg?tctggccagt?acttttgacc?tcttagatgc?aagtgggaaa?ctttgggggg??76980
tatgcatggt?gagtttagtc?agtagtatcc?acactaggtt?ttattatcct?gctcttttgt??77040
ttttaaagat?attttatttt?atttatttat?tttttcaaga?tggagtctcg?ctctgtcacc??77100
caggctggag?tgcaatgcca?caatctcagc?tcactgcaac?ctccgccttc?tgggttcaag??77160
tgattctcct?gcctcagcct?cctgaataac?tgggactaca?ggcgcctgcc?accacacccg??77220
gctaattttt?tgtattttta?gtagagacgg?gatttcaccg?tgttagccag?gatggtcttg??77280
atctcctgac?ctcgtgatcc?acttgccttg?gcctcccaaa?gtgctgggat?tacaggcatg??77340
agccaccgca?cccggcctaa?tttttatatt?tttagtagag?atggggtttc?accaggttgg??77400
ccaggctggt?cttgaactcc?tgatctcaga?tgatccacca?gcttcggcct?cccaaactgc??77460
tggaattaca?ggcgtgagcc?accgcgtctg?gcctaaagat?attttaatat?caaaagtgat??77520
actgtataag?ttactattat?ttatttctgc?atatggacag?tcctgaagaa?ataagagaaa??77580
agatcttgaa?tttctttgac?cacgttttaa?caaaaatgaa?gacatctgac?gaagacatta??77640
tccctctgga?atcttgccag?tgtgaagaaa?tcctagagat?tgtcatcttg?cctctggccc??77700
accattttct?ggctttggga?gaaaatgaca?aagccttata?ttacttctta?gaaattgcat??77760
ctgcttatct?catcttttgt?gataactaca?tggtaagctg?tttctaccca?gaccacctcc??77820
accctagaga?caattcatag?aacatagagc?cagaaggaag?ctccagcatg?ctttctgatt??77880
acttcacgtt?gtatattccc?gacagcaccc?ctttccactg?aaaatcacat?tgcttagaag??77940
ggaaatgatc?taagattgag?aaaagagaat?tggaatacat?tgcaactagc?attgtaaatt??78000
atttaaaata?ttgccacctt?tagaaacttg?ccatgaattg?tctacctgta?tgggaggtaa??78060
gggggcacat?ctcattccca?aaatgatgca?gagaggactc?tcagcatagt?cttcctcaag??78120
tggcatttac?cctctgttaa?gcctaaaata?cctgtgagca?caaaatacct?gtaggtcttt??78180
ggataagtgc?aattctggtt?ttttgttttg?tttttgagat?gaagtctttg?tcacccaggc??78240
tggagtgtag?tggcgcgatc?tctgctcact?gcaacgtctg?cctcccggga?tcaagccatc??78300
ctcccacttc?agcctcctga?gtagctggga?ctgcagacgt?atgccaccat?gcccagctaa??78360
ttttttgtgt?tcttggtaga?gatggggtta?cactatgttg?cccaggctgg?tcttgaacac??78420
ctgagctcaa?gggatctgcc?ctccttggcc?ttccaaagtg?ctaggattac?aagtgtgagc??78480
cactgtgccc?agccaattct?ggttttaata?ttgtgatccc?caaagaggct?ctccctgcct??78540
ttgtcatcat?gcaatgtgtg?ctagattatt?acacatacca?ttagaccacc?aaagcactag??78600
tgaatgtttc?tctagggtaa?ttataaataa?ggttccaggg?cactatgccc?atagaaatga??78660
ggggatttga?tacacatgat?gaaataaaca?gaattcattg?ttaagtaagt?tggaaatcac??78720
tgagctgaat?acaggtaaat?agatgccttt?agatacttca?gggcctttga?tatgctgaga??78780
tatatatata?aatctgttca?gaggacacag?aagggtaaag?gccaggctag?gctgaagcat??78840
actgtgtttc?tcaaacttat?ttgcccttag?atctcttttc?atggagcagc?tggctgggct??78900
aaccttccat?gaactcactt?gaggaaatgt?ctttctgggc?ccttgcttca?tctgacttca??78960
gccagcttca?ggaagagctt?catagacctt?ccataattta?cagttgctac?tggtcacagc??79020
agcctaatca?accctcctac?cttagattta?tataaaatta?taaaattaaa?ctgttaaaaa??79080
tgtcactaag?ttcctgtcct?tgaaacattt?atgttaagaa?tgaaagtctc?ctgcatattt??79140
catgcacata?ttcgaggtga?tgatggggat?gtagccaatg?agtcccagga?ggaggaggct??79200
taggtagccc?tgggggccaa?ctttctaaaa?cctatgcata?ccccgtttca?cttgacaaga??79260
agacaatgat?tagaagcaca?gcctcagtgc?aaggtcccag?aatgtgacat?ttgtaccccc??79320
tctcccatca?aactccagtg?ggactggggc?tggtggccaa?ctcatcatgt?ctccctcttt??79380
ttttgcctcc?cacacatacc?caacaggatg?catgagactg?ggagatactg?cctcacctta??79440
ttatattctt?caagtctgat?cttaccttgg?tgtgcacacg?tgctaagatt?tgcctaatga??79500
tgttgggagg?tgaagctgaa?gtgatgagag?ttgtgcaggg?acttacttcc?tcatccacct??79560
cccaaaatga?ccctggcaaa?ggaagtgggg?gtgattcata?attcatttaa?aaactgaaga??79620
ccaacttctc?acagatgtgg?ggatgctgtt?caagggaagt?ggatgtgttg?ttgggaatag??79680
ggaggttggg?gatagaatta?ttgagaggaa?gaaactggct?tgagggaaac?ttcgggtaag??79740
gcaacctaga?tgatagtgtg?aagaaaggtg?gagatttcca?gattcattct?cttgatggag??79800
tgatccagca?gacaaaggta?agcatgaagg?tgagatcttt?acccatcagc?tcctgtctgg??79860
aatttggaag?cccattttaa?tcagtggagc?tggggatgga?agtggaggtg?gtaactgaaa??79920
tggctcctgc?atctcttact?tcagtagagt?ctggggcaat?ggcccttctg?tgggctcaat??79980
ccctgctgaa?tcaacacttt?tctactcctt?gggctggtta?caggcataca?tgtatttgaa??80040
tgaaggacag?aagttgctaa?aaactctcaa?gaaggacaaa?tcttggagcc?agacatttga??80100
gtctgccacc?ttttacagcc?tcaaaggtga?ggtaagaaac?cattaaagac?ttgaatttat??80160
ctgttatata?tcttaggcct?ttccatagaa?gtagaagtca?tccctatact?ttctacaccc??80220
tcctcccatc?tcttgccaca?gacttctagc?caagactcta?gaaactcaaa?tccctgggct??80280
ccaacctcct?caccatggct?taccagcaag?atcttccctg?tcttccaggt?ttacatcttt??80340
tttttttttt?ttttttgaga?gggagtcttg?ctgtgttgcc?cagcctggaa?tacagtggcg??80400
tgatatcggc?tctctgcaaa?ttccgtctcc?tgggttcaag?tgattctcct?gcctcagcct??80460
ccaaagtagc?tgggattaca?ggcatgcgcc?accacgccca?gctaattttt?gtattttagt??80520
agagatgggg?tttcaccatg?ttggccaggc?tggtctcaaa?ctcctgacct?caagtgatcc??80580
gcccgccctg?acctcccaaa?gtgctgggat?tacaggcgtt?agccaccgtg?cccggcccag??80640
gttgacacct?ttatgaaata?tttttgttac?aatctctaaa?aatggacctg?aatgggtaaa??80700
cattgtctca?gaggtagaca?atgcacaact?aagatgctaa?atcctagtca?ttcaaccacc??80760
cttcatgcat?atatccaata?gacattttct?attatgccag?gcacaggaag?attttgtttc??80820
tggtccataa?attacctttt?ttgataagaa?tccccaaaat?atggattgtt?gggacctact??80880
aattaagtta?gaatcatcgt?tttcctcttt?tcctctcttc?cctcccacct?ccctgtaggt??80940
ctgtttcaat?atgggccaga?tagtgcttgc?caagaaaatg?ctgaggaagg?cactgaagct??81000
cctcaaccga?atctttcctt?acaacttaat?ctccttgttt?ctccatatcc?atgtcgagaa??81060
aaacagacac?tttcattatg?tgaatcggca?ggcccaagag?agcccacctc?cagggtaagg??81120
gaaggagctg?gggagagcag?actgtttagt?ctcactcccc?agagaggcct?acacataatc??81180
caagtcagcc?cccaaagcct?ggcctccagg?gggcacaagg?actcctgttt?ggctctgacc??81240
attcactggg?gagggggcga?gtgtgggagg?tgctcccata?ccagggttgc?cacaaagtac??81300
tttacaggca?gtttttgcca?aagggaattt?tgatgactca?aacataaggg?acctcgttgt??81360
aaggtaagtt?ctagggtccg?tcctaactca?tctagccctt?taacccccat?ggccatccgt??81420
gttctcattg?gatggaacct?gcaccactgc?tcctgggacc?tcagtcacaa?gccctcttcc??81480
attaggtgct?aagacactgg?gttttgcccc?gccccaaaga?aaaatagcaa?gccctgaaga??81540
catttgccaa?aggacaaaac?tcccacccat?ctaggaatct?caatagggat?atgggttaca??81600
tggggggtat?ccgttggtca?aaattgtact?gttaagattt?gggcatttca?atatatataa??81660
attctaccta?taagataact?ataataataa?tgagtgggaa?gaaatagtga?gtggagaggt??81720
agatgaaata?agcatgttgc?tagttgttga?aggtaggtgt?tgagtgcatt?ttgctcatca??81780
tactcttgtt?tgctgtgtgt?atgcttgaat?tattctataa?taaatgtttt?caaaaatatt??81840
ccacctatct?agcaattcat?ggcaaaggag?atgcctcctt?gttgggtacc?tggagagctg??81900
acagaggaca?cctcttccat?cttgggggag?ctctgtagct?atattactat?aggttctgcc??81960
taagatacaa?acatctattc?ctacgagcaa?gctactacaa?ctcttttgca?accccatcag??82020
aaactgcctt?ccccagcttc?caaacatgtt?cctttaaatg?tagggaatcc?tgaggtgaaa??82080
aggaaatgta?atggagctga?gctcctgtgc?acgttggagg?tgggctcctg?ggaaaacctg??82140
gctgtttctg?gaaaccccaa?gaggaagggc?tgggagatgt?tcagcagaga?tctctctgag??82200
aaggcagtgg?tctttgcatt?acacataggg?ttgcaggatg?cctcaatttg?aatttcagat??82260
aaacagtgaa?tacttttttt?agtatacatc?tatcatatga?aatatttagg?acatatgcat??82320
tccataaaaa?ttattaggtt?taaaattcaa?acttaattgg?gcatcctgta?ttttcatctg??82380
ctaaaacagg?taatttacac?atttcacatt?ttgtaaaagg?agtaagaagt?acctgcacaa??82440
agggaaaagg?tagaaaagtg?ttgaagaaga?aaaaactgag?gagctgttgg?cttaaaatat??82500
ccacaggtca?aaaggttctc?atctcaaaaa?tgagtatgac?atggaacaac?atttaatgtc??82560
agagtgtcca?tgaccctcac?gaatgcccta?taagagattt?tacccagggc?tgggtgttgt??82620
ggctcacgcc?tgtaatacca?acgcttaggg?aggctgaggg?gggcggattg?cctgaagttg??82680
ggagttcgag?accagtctgg?ccaacatggt?gaaatcccgt?ctctactaaa?aatacagaaa??82740
aaatttagcc?aggcgtggtg?gcgtgcacct?gtaatcccag?ctactcggaa?ggttgaggca??82800
ggggaattgc?ttgaaccagg?gaggtggagg?ttaaagtgag?ccaagatcgc?gccactgcac??82860
tctagcctgg?gcgataaagc?gagactccgt?ctcaaaaaaa?aaagagagag?agattttacc??82920
ctgtccatgt?ttcctaagaa?cctttaaaaa?aaatcatttc?cacatcataa?tttagaaagt??82980
ttattttgcc?aaggttgagg?acacgcctgt?aacacagcct?cagtaagtcc?taacgacatg??83040
tgcccaaggt?ggtcggggca?cagcttaatt?ttatacattt?ggggagacag?gagacatcaa??83100
tcaacatatg?taagaagtac?attggtctgg?aaaggtggga?caacttgaag?caaaggcagg??83160
aagttgggag?ggagcttcca?ggtcacagat?aggtgagaca?aaagttgcat?tcttttgagt??83220
ttctgattcg?cctttccaaa?ggaggcaaat?cagatatgca?tctatgtcaa?agggcagagg??83280
agtgactttg?aatagaatgg?gaggcaggtt?tgccctaagc?agtttccagc?ttgagttttc??83340
cttagtgatt?ttgggggccc?aagatatttt?cctttcaaaa?tgcaatagtt?aaaaatgctc??83400
attttttggc?caggcgcagt?ggctcacgct?tgcaatccca?gcacttcggg?aggctgaggc??83460
aggcggatca?cctgaggtca?ggggttcagg?accagcctgg?ccaacatggc?gaaaccccat??83520
ctctaccaaa?aacacaaaat?aattagccag?acatggtggt?gtgtgcctgt?aatcccagct??83580
actggggagg?ctgaggaaag?agaatcgctt?gaacctggga?agcagaggtt?gcagtgagct??83640
gagatcatgc?cactgcactc?caacctggac?aacagagcga?ggctcaaaaa?acaaaaaatc??83700
ctcttttttt?ttttttttgt?aaactaaaaa?gtacccaaga?caggtatcaa?tcaatctgta??83760
agtttatttt?gccaaggtta?aggacatgcc?cagaagaaaa?aaaaacacaa?aaccacagaa??83820
acagtccctg?tttgagactg?cagtatttaa?aggggaaaag?tgggctggag?gaaaatgagg??83880
gagggcgtga?taataatcca?catgttgcaa?gagaatagga?gcagctaggg?gaatagtcaa??83940
ttatgtattg?tctcacactc?agtaaatagg?cacttaaggt?aggataaggc?agacatagag??84000
tagctacccg?tgcagatact?taacttttta?tctgtagctg?tctgctaagg?aacaaaagga??84060
aaggcaactt?cttgcatgac?tcagctttca?gcttaatttt?ttccttttgg?catagtgaat??84120
tgggatcctg?agtttttatt?ttcctttcac?acctttgttg?agctgagaag?tagttcctga??84180
aagcagtgtg?caatggagaa?aataatacat?tgggcttttg?ggctggaggt?agatggagtt??84240
tgaatcctgg?caccaccaca?ttccagctgt?gtgtctttgc?cttaattact?taacctgagt??84300
ctcaccttcc?tcaaatgtaa?aatggagtca?gttattccac?tcttttctta?caggattgtc??84360
atcagaatca?aatgtgatga?ataatatcaa?tgtgcttttt?aaatagcttc?atttagcaat??84420
tacctgactc?aggacagatg?ctttacataa?attatcttaa?tcattataaa?gtaggtatta??84480
tgattcccat?tttacaatga?agaaaatgtg?ctccataaaa?attaatgtgc?ttgtttgtca??84540
gtcatggaga?caggcctcaa?attcaagtca?gttttgattc?ccaggcccat?agtgaggaca??84600
ccatgtacct?gtgctcccct?aaatcatggt?aatgatgata?cctttcatgt?tccatttgtg??84660
tttaccttat?ccaataggaa?gaagaggctg?gcacaacttt?accggcaaac?tgtctgcctt??84720
tccttgctgt?ggcgcatcta?tagctacagt?tatctttttc?actgcaagta?ttatgcccac??84780
ctggcagtta?tgatgcaaat?gaatactgca?ctggaaactc?aaaattgttt?ccaggtaggg??84840
gatttttgta?gctgctcctt?taagtttctg?aatttcattt?gggaagaaaa?gcctagtgaa??84900
agccaattag?gattcaaaat?tctgaggata?taataataga?aggctttctg?attggcttgt??84960
tttgacaagg?ccagcagttc?tcaaacactt?tggctccagg?atcacttcac?actcttaaaa??85020
attattgaag?atcccgaata?gcttttattc?atatgggttg?aatctattga?tagcatataa??85080
gaaacaaaag?tcgagaaaat?tctaaaatat?tattattatt?atttttgctg?gttttttttg??85140
agatggagtc?ttgctctgtc?acccaggctg?gagtgcagtg?gcacaatatc?ggctcactgc??85200
aacctccact?tcccgggttc?aagagattct?cttgcctcat?cctcctgagt?agctgggact??85260
acaggcatgc?gccaccacac?ccagctaatt?tttgtatttt?tagtagagac?ggggtttcac??85320
catgttggcc?aggctggtct?tgaactcctg?acctcaagtg?atctgcccac?actggccttc??85380
caaagtgctg?ggattacagg?cgtgaggcac?tgcacctggc?ctaaaatatt?attttaaaat??85440
aaagataaca?agcctattac?atattaacat?aattaccatt?ttcatttttt?aaaactctgt??85500
tccgcaaaca?aaaaatggga?aatgtggcat?tgtattaaat?ttttgccaat?attttaacat??85560
ctggcttctt?agaagacaac?tagattctca?catctgcttc?tgctttcact?gttgcagtat??85620
cacatatgtt?gcctctggaa?gactccagtg?tatattcatg?agagaatgag?ggtgaaagag??85680
aaaaatgtta?aaggataatt?cttttttaaa?aagatagaat?tataactgat?aacaaatatg??85740
gaaagtacac?atcaaagatt?ttatttaact?cactgagttg?actcaatcaa?aattagtaag??85800
attggaacca?agtggttcca?aggagaatct?gtttaccaat?ggatacaaaa?cttgtctagt??85860
aacagcataa?taatcacttg?tattccactg?aatatttaca?tttctatgaa?aaacaaatca??85920
tatcacttat?attaatatca?gttttctgca?acatagttgt?aagatagtcc?aaagaaaaat??85980
agagataact?ttgattagta?agctagatag?gatccccact?aagttgtgtt?tttgcccatt??86040
ttaaggtctt?tcactatttt?tcctgtcaca?aataatgcct?ggatattagc?ggggcatggt??86100
ggctcacgcc?tgtaatccca?gcactttggg?aggctgaggt?gggcggatca?cgtgaggtca??86160
ggagttcgag?actagcctgg?ccaacatggg?gaaaacctat?ctttactaaa?aatacaaaaa??86220
ttagctgagt?gtggtggtgg?gtgcctgtaa?tcccagctac?tcaggaggcc?gaggcaggag??86280
aattgcttga?acccaggagg?cagaggttgc?agtgagatga?gatcacacca?ttgcactcca??86340
gcctggatga?caagagcgag?actccaactc?aaaaaaaaaa?attttttttt?tttaaattta??86400
aaatgcctag?atattatgga?actagctttg?acctcatgtg?gtctctgaaa?aggtgccacg??86460
gatccctagg?gctcccagga?tgaattggga?gaaccactag?tctaggtcat?aaccaaagaa??86520
gcctttgact?ggatgaagaa?gatatcagga?gacatgatca?agaaattatt?aagctaaatc??86580
aaactcatct?aatgagagtg?accttgctcc?tttataaaag?tacattaaat?cagcaggccg??86640
ggcatggtgg?cttatgcctg?taatcctagc?actttgggag?gccgaggtgg?gcggatcaca??86700
aggtaaggag?atcaagacca?cggtgaaacc?ctgtctctac?tgaaaataca?aaaaaaaaaa??86760
aaaaaattag?ccgggcgtgg?tggcgggcgc?ctgtagtccc?agctactcgg?gaggctgagg??86820
caggagaatg?gtgtgaaccc?aggaggtgga?gcttgcagtg?agcagagatc?actccactgc??86880
actccagcct?gggcgacaga?gcaagactcc?atctcaggaa?aaaaaaaaaa?agtacattaa??86940
gtctgggttt?cttcctcctg?gagtcattag?ttgtcaagaa?ttaagggaag?gggtcaagta??87000
gcaccaagga?gctactgttg?gaggagctta?gattcctaac?ctggagtctg?tcctctacat??87060
tagttccttt?tggtgaattt?aggctggctc?tcctagaata?cagaagtatt?tataaagccc??87120
atcaagattg?acccctgcct?atttcccatc?ctcttctagc?tctgtaggcc?atgaagtagc??87180
cacaagccca?gccatattgg?tcctcttttg?gttcctcaaa?cacagaagtt?taatcccatc??87240
tgtcactgga?tgtttcctct?gcttggaggg?aactggtcat?ggccacccat?tcactttcta??87300
acttgtcact?ctgttttaat?aggtattatt?accatttgac?aatttcttgt?ttgctcctgc??87360
attggttctt?ggtctctctc?ccttaccagt?gtgtaaatcc?cttggaagca?aggacctctt??87420
cagctgtctt?gttcacatcc?taagtttcta?gaacatttgc?agttgctcaa?gaaatttata??87480
tggactgaaa?tacttctcca?cacttggagc?tatatcctaa?gaattgtggt?agagttgggg??87540
tggggaaaat?aaaaagtcag?gatagaatgt?gaaccaagac?atttgtcatc?aaggtggctg??87600
ggattgaaag?caaagaagcg?ctcccctcag?tgctcaaagg?caggtgaggg?actcagcatg??87660
ggagaatgga?aagaaccaga?ctgagagcca?gagggtggtt?tccaggactc?cgcctatctg??87720
cagtgtgacc?actgaaaagc?cgcataaaca?aggagcttta?tattttctct?gtaaagtgaa??87780
gcagttggac?ctccattctc?ttggtccaaa?tccaagaggt?cctaggcttt?attacagcct??87840
tggatttctc?gtgcccaaca?cttctctctt?cccccaccac?catttctggc?tatccttacc??87900
ttctggtagc?attatctgga?acatgttcca?aaccagaaag?aaaggaattc?tctaagactg??87960
atgtggttta?agtatccagg?gacctgccta?taacacagaa?tttgtaggct?gcttattttg??88020
tcccatctga?ggaattccaa?gaaaaaagcc?tctactctaa?aacacttccc?cgaccccaat??88080
actcccacca?ctagagatac?tttatttttc?ctgtttgtat?ttttcaaagt?agtttacatg??88140
tattattttg?tttttgtata?tataataaaa?ctgcttcttt?agaaggaacc?cttttctcct??88200
cactattctc?taagcatgta?tactctgaag?caactttatc?tttttaaaga?gttgtttaga??88260
gtaaccagtt?tctcttaaat?ctgcaaatta?gatttatttg?tttgttcgtt?tttgagaagg??88320
gtctcactca?gtcacccagg?ctggagtgca?gtggcgtgat?catggctcac?tgcagcctca??88380
acctcccctg?ctcaagtgat?cctcccaaac?acctcagctt?cctgagtagc?taggattaca??88440
ggcttgtgtc?atcatgctgg?ctactttttt?ttaaaatctt?ttgtagagat?caggtctcac??88500
tatattgccc?aggctgggct?caaactcctg?tgctcaagtg?acctctcgtc?tcagcctcct??88560
gagtaggtag?gactacaggc?atatgccacc?atgcctggct?agtttttgtt?gttgttgaaa??88620
cagggtctca?ctattgtgcc?caggctcatc?tggaactcct?gagctcaagc?aatcctcctg??88680
cctcggcctc?cagaagtgct?gggattatag?atgtgagcca?ctgcacctga?cctccaaatt??88740
aggtttaaaa?ctagtcctta?tttaaaaaaa?aaaaaaaagc?caaacaaaca?aaaccaacct??88800
ttctttcttt?tttgttaaat?tacaaaaatt?atacatgctt?gttataacaa?acatcacaga??88860
ggtgcataaa?gtaaaatctc?tcctcccacc?cccaacaaat?atataactac?tgtttacact??88920
ttggagtgta?tccttgcagc?ctttttgctc?tgcaattata?catctaatat?gtaagctatt??88980
gcttttattt?ttcacagaaa?ttaaaatttt?tatatttcat?ttaaggacta?catgggcaag??89040
gggccatcaa?gcttatcctg?aatgactcag?taaacaggta?gcagaaaccc?aatttgattt??89100
ctatttctaa?gcccatggct?tcggccaaat?gtccagctct?attcccaaac?ttaataaaca??89160
aacatttact?ggcagacatt?gagtgatgtt?cctgagcttt?ctgctttgcg?ttctgcctca??89220
ctcttcctcc?actctgccat?ttcagatcat?taaggcttac?ctagactatt?cgctatacca??89280
ccacctggct?ggctacaaag?gtgtgtggtt?caaatatgaa?gtcatggcca?tggagcacat??89340
cttcaacctc?cccctgaaag?gcgagggcat?tgaaatcgtg?gcatacgtgg?ctgagacact??89400
ggtcttcaac?aagctcataa?tgggacacct?ggatttggcc?attgagttag?gtaagggctg??89460
gctgggcaag?atgggacatg?aggatacaag?gaatgcccca?caatatactg?gaattgtttt??89520
cttcccaggc?tcccgagccc?ttcagatgtg?ggcactgctc?cagaatccca?accgacatta??89580
tcagtccctc?tgcagactta?gcagatgtct?ccttctgaac?agcaggtatt?tatcttaaag??89640
cattttccaa?aattaggggg?aggaggccgt?attattgagt?attctgggtt?caactttagc??89700
ctagtcctag?ggtggggaag?ggagtagagt?ttgcagtaag?aaaatgtaac?tgatagtagt??89760
cacccttttt?tcttttttca?gacagagtct?tgctctgtct?cccaggctgg?agtgcagtag??89820
tgcaatcttg?gctcactgca?acctctgcct?tccgggttta?gacaattctc?ctgcctcaac??89880
ctcccacgta?gctgggatta?caggcaacgt?gccaccacac?ccagctaatt?tttgtatttt??89940
ttagaagaga?gggggtttca?ccctgttggc?caggctggtc?ttgaactcct?gacctcaagt??90000
gacccaccca?cctcagcctc?ccaaagtgtt?gggattacag?gcatgagcca?ctgcgccagg??90060
ccttgtcttt?tttattttaa?acagaattct?ttgccttgca?tcatctctaa?tctggttgct??90120
ctggccagtg?atcagagggt?agtcagacag?tcatcccagc?tgtgggaatc?aggcctccac??90180
ttctgtcagg?tggagacaaa?gggaaaagtc?ttccagggag?gcaaatggcc?agagaatagc??90240
aaccaggact?agaggtcaag?gccaatttgc?tctgactctg?gtcaccctga?tatagaggac??90300
ccaggaaaga?acaatttgaa?aaaagagcca?atttgagatt?gaggttttag?tcctggatag??90360
gggtgtgttt?gaaatctgtt?taagaggtat?atttggttcc?gaattactga?gaaggaccaa??90420
gactagacca?ggaagggact?ttactgaacc?tcatcctatc?cactgctttt?tttattcaat??90480
agctttgggg?gtataaatgg?ttttcggtca?catagatgaa?ttttatagag?gtgaattctg??90540
agattttagt?gcacctgtca?cccgagcagt?gtacacatac?ccaacatgta?gtcttttatt??90600
cctcacttcc?ctcctcccct?cccctccgag?gccccaaagt?ccattatatc?cactgctttt??90660
tttttttttt?ttttttgaga?tggagtttcg?ctcttttgcc?caggctggag?tgcagtggtg??90720
cgttattggc?tcaccacaac?ctccgccttc?tggtttcaag?cgattctcct?gcctcagcct??90780
cccaagtagc?tgggattaca?ggcgcccgcc?accatgccca?gctaattttt?gtatttttag??90840
tggagatggg?gtttcaccat?gttggccagg?ctggtctcga?actcctgacc?tcgtgatcca??90900
cccacctcag?cctcccaaag?tgctgggatt?acaatatcca?ccacttttta?atggccacta??90960
ccttttcttt?tccatagata?cccgcaattg?atccaggtgc?tggggcggct?gtgggagctt??91020
tctgtaacac?aggaacacat?cttcagcaag?gcatttttct?attttgtctg?cttggacatc??91080
ctgctttatt?ctggtaagtg?tgggtttggg?atgtaaaaga?acttgggggt?gttgatacct??91140
gtgctggtgt?ggtgtggcag?ctctcaggtt?ggggctttgg?gaccactagg?tttctggctg??91200
gtggacttac?agggcaggga?tggagagagg?ctggttgtgt?gagctgaagc?actgtctagc??91260
aggtgccgag?attgtaaagg?cacggcaaga?aggagaatta?agtctgaagg?aacctgatgg??91320
atatgagctg?ccagttaaac?tgtcagatca?atttgcacct?aagtgatagt?ggctgactgt??91380
cttactatgt?gccttttacc?aggggttttt?aacttttagc?aggatgtact?tagagacttc??91440
acgctttaga?atgaaggact?agattgcttg?aggtgagagt?tccaggctgg?tagctattgg??91500
tgatttggaa?aataagttac?ttcctgataa?ccttcaagtg?acaccaagta?ggtcacttga??91560
agtgtacaca?ctaaaccaca?ggaaccaacc?tgaattgttt?tccccacatg?tgatcttgaa??91620
aggggatgca?gacattgcca?tcaacaaagg?aagcatgtgt?ggagagacag?agaagtccta??91680
ggctgcacta?aggccaggaa?ggattagttt?aaaccccaca?cctgcctggt?cggtactgtg??91740
gaactgtagt?atatatccat?aacactcccc?aataggtagg?actcagcaaa?cacagggcaa??91800
tccagtcatg?aggttgttgc?aatccacggg?accctctgga?ttcatacaat?aatcagaggc??91860
aactctccct?gcagtgggaa?attcaactga?gagtgactag?gctagaaaga?tgatcaccca??91920
cacctactaa?taactctcac?ccattcctct?ctctcttagg?ttttgtttat?agaacatttg??91980
aagaatgttt?ggaattcata?caccaatacg?aaaacaacag?aatcctcaag?ttccacagtg??92040
gactcctcct?gggactttat?tcctctgtag?ctatctggta?acaatgtgtg?gcatatcact??92100
aaattcccaa?agtgaaaatg?ttgaatccca?aggaagagtt?cttgaaaaat?cttttagaaa??92160
gtattcataa?tttatacctg?agacagctta?agggtgtcag?aggatattta?cacagagaga??92220
catgttaggg?atcaactagt?tcatccccct?tggccaagga?cagaaaagta?aatttatctc??92280
aattacatcc?atgcaataaa?catttatcgc?aaacatatca?tgttgtggtg?atacagggat??92340
aaataagaaa?agattgcttt?cttcagaggg?gtgctggggt?ttgaggaaga?ctaatgaata??92400
gcaccacttg?cccacccggc?acctgcccat?atctaatcac?atggattgac?aaagccaatg??92460
ttggaagaca?tggcttatat?cttcacgaaa?gcgggcttcg?taatattgag?cactggaatt??92520
agacttaacc?cattcagcag?caggcagttc?tggaaaactg?taggtctact?cacatggagg??92580
caggcctctt?gtagcagaga?gatcagtatc?acactccctg?ttggcttcac?tggctctcaa??92640
gatagagaga?gacacggact?gagttatact?tgcccaattc?atctcccaaa?tcaccagcaa??92700
gatctctcct?tatcattgaa?agggcaagta?aagcggggaa?agagttctgg?tgctttgcac??92760
caaatagagg?ccccttacat?ggaaggaaat?ttcaggagtg?aggaagcagc?attctccccg??92820
caccccatta?actcattaag?cctaaggctc?aattccttta?acctactacg?tttttaactc??92880
agttaagcat?gtagctatta?tggtcatacc?cttaaggaag?gagatgaatg?ctaaggttct??92940
aaaatgggtc?agaacagaac?attcattaaa?ttatttccat?gactatcccc?aagactgaaa??93000
atcgccccct?attattttat?ttcctatctt?aattatatgc?aaccgtatgg?tctatcagag??93060
gtttgtgatg?agactaaatg?acaatatgaa?gacattccta?tataaaatgc?tacaagttag??93120
aacagctcca?aattggaata?gaaatccacc?ccttccttct?ttctgagaca?gtcttgctgt??93180
gtcacccagg?ttggagtccc?gtggtgcgat?cgcggatcac?tgcagcctcg?ccttcccagg??93240
ctcaagtgat?cctcccaaac?acctcagctt?cctgagtagc?tggagttgca?ggcacatacc??93300
accacgcctg?gctaatttta?atcttttgta?gagatgggat?gtcgtgatgt?tgcccaggct??93360
ggtctccaac?tcctgggctc?aggtcccgtc?tacctcagcc?ttcccaaatg?ctgggattac??93420
aggcatgagc?cactgcacct?ggcaagaaat?cccctcttat?tattaaaatt?aatgaggaga??93480
aattaaaatc?caaaaattga?ttactcttgc?caattaaagt?tcaaaatcaa?ataacttacc??93540
aatgtgagtt?aaaggttaag?gaatctaaag?tccagaaatc?atccaaattt?atttttcttg??93600
tctatctcag?caggagaatt?ttttaaacag?ctgtgtccta?ggccaatgct?gctcagactt??93660
tagtgggcat?aaaaatcacc?tggagggcag?tcggccagct?ctcggggtgc?tgagccaggc??93720
gggctaggcg?aggcgcgggc?tggccccgcc?cctctggccg?gccccgcccc?tcaaggccgg??93780
ctagtcccct?tcccagagac?ttggctaggc?ggccggcgct?gcggcgccag?cagccctgtg??93840
gtggcgacga?cgatggacca?ggacccagtg?ggccctgtgg?aacgaggaga?agccgtcgca??93900
gcctcgggag?ctgcggccgc?cgcggcattc?ggggaatctg?cggggcagga?aattaaggga??93960
tccaaaaagc?tgagtcatgg?tccaaaagga?aacgttgatg?tcaggacaac?catagccaaa??94020
ttttatctca?aggatgagta?acgaaagagg?ctttgaaacg?tagaactggg?agtcatagga??94080
aaaaagaaga?aagtcccaag?gagagtcatc?cactttgtta?gtggcaaaac?aatggaagaa??94140
tacagcacag?atgaagatga?agttgatggc?ctggagaaga?tgttttgcct?actgttgatc??94200
cgatttggct?ttaaatattt?ggctattaga?aaatcatgcc?gggcgcggtg?gctgacacct??94260
gtaatcccag?cactttggga?ggccgaggcc?ggcagatcac?ctgaggtcgg?gagttcaaga??94320
ccagcctgac?caacatggag?aaaccccatc?tctactaaaa?atacaaaaaa?attagccagg??94380
catggtggcg?catgcctgta?aacccagcta?cctgggaggc?tgaggcagga?gaattgtttg??94440
aacccaggag?gcgaaggttg?cggtgagcca?agatcgcgcc?attgcactcc?agcctgggca??94500
acaagagcaa?aacttgggtc?tcaaaaaata?aaaaaaaata?aaaaataaaa?aaatcataag??94560
caggccagga?gcagtggctc?acgcctgtaa?tcgcagcact?ttgggaggct?gaggtgggtg??94620
gatcacctga?ggtcaggagt?tcgagaccag?cctggccaat?atggtgaaac?cgtgtctcta??94680
ctaaaaatat?aaaaaattag?gcaggcgtga?tggcaggcgc?ctgtaatccc?agcgaggcag??94740
gagaattgct?tcaaccaggg?aagcagaggt?tgcagtgggc?tgagatcgtg?ccattgtact??94800
ccagcctggt?caacaagggt?gaaactccat?ctaaaaaaaa?aaaaaaaaaa?aaatcggatt??94860
ttctacacag?aaaatattca?aaggattgta?ccatatactc?tgaaggtagt?tccaaatgca??94920
ggtagaatat?taaagaggta?tttcatgcaa?tgtaagaatt?gttggaataa?atgtcttatt??94980
tttaattact?ttgaagggtt?aaaaaaaaaa?tcacctggag?agcttgttaa?ctcagagatg??95040
ccacaccccc?agagcctgtc?tgattcagta?gacctggact?gaaccagaga?acctgcatta??95100
atgagaatcc?aggtgatact?gatgatgcca?gtctgtggac?tacattttga?gcagtactgg??95160
cctaaatcat?ctctctttgg?tattggaaca?atttcttcaa?gccccagaat?ccacagctcc??95220
aagtgtctga?tctccctcac?tttttaattt?aaaaagccaa?agtggccggg?catggtggca??95280
cagcctgtaa?tcccagcact?ttgggaggcc?aaggcgggtg?gatcacctga?ggtcaggagt??95340
tcgagaccag?cctagccaac?atggtgaaac?cccgtatcta?cttaaaatac?aaaaaattag??95400
ctgggcgtgg?tggtacacac?ctgtagtccc?agctactcgg?gaggctgagg?caggagaatc??95460
acttgaaccc?aggaggcaga?ggttgcagta?agccaagatt?gtgccattgc?actccagact??95520
gggggacaag?agcaagactt?cgtctcaaaa?aaagaaaaaa?agccaaagcc?aaagagttca??95580
atggtggcta?atattacctg?agtgtttcca?aggattctat?tcatctcaag?tcatcaaaaa??95640
aatttattat?ttccttgctc?tgtatcacat?aatttcctgc?ttttttaggg?agtgtgaagc??95700
aggggtaggc?aggagactac?acacttccag?agacccaggt?aaaggaagct?gcacatccag??95760
agagacattt?cagaaagcca?gcctattcct?aatgggtgat?actgattttt?cttattctct??95820
tgtggtaatg?caggtatgcc?agacttcagg?aatgggacaa?cttttacaaa?ttttccaata??95880
gagctaaaaa?tcttttgcca?agaagaacca?tgacacttac?ttactatgac?ggaatatcta??95940
ggtacatgga?ggggcaagtt?cttcaccttc?aaaaacaaat?caaagaacag?tcagagaatg??96000
cccaagccag?tggggaggag?ctactcaagg?tgaggcctat?tctccagttt?ccagtataaa??96060
atatgcctta?aatggatctc?tgtctacttc?ctgtgctaat?tattttctca?ttatagaatt??96120
catatatttt?tataatagaa?gtttttgaag?gcacttcccc?aaagtaagaa?agaaaatata??96180
aattgcccat?aaccttacta?ctcagagata?agtacttttt?gtatattgag?atcccacttt??96240
tcaagtattt?ttctgtgtgt?gtgcatgcac?atttctctat?tttgtaattt?gctattaaat??96300
atattatgaa?taatttcctg?tcattaaatt?gtttttcaca?tcacgattta?aaaggaagca??96360
tggtacttta?tcttacagat?atatgattgt?atggcctaat?tattattgga?tagaactttt??96420
ctgtatgatt?ttattgctat?tgctgtgata?aagcatcctg?gtagacaaat?cattccacac??96480
gacaatttaa?aaaattcaaa?tatgtattaa?gcatattaat?acaagagtgc?tggggcgcaa??96540
gagtgagcaa?attaaacacc?tccaagagtt?tacaacctgg?catgggcaag?cccccaagag??96600
aataaagggc?taaatctctg?gtgttgggtt?gacacgtttg?ccttgttctt?gtaaacactg??96660
agcacaggtg?tactagtttt?ctattgctct?gtcactcatt?accacaaagt?aaacagctta??96720
aaacaacacc?cacttcttaa?cagagcctcc?ctttgtcacc?caggctggag?tgcagtggcg??96780
caatctcgac?tcactgcaac?ctccgcctcc?cgggttcaaa?caattctcgt?acctcagcct??96840
cccaagtagc?tgggattaca?ggcacgtgcc?accatgcctg?gctaattttt?gtatttttag??96900
tagagatggg?gatttcacca?cattagccag?gctggtcttg?aactcttgac?ctcaagtgat??96960
ccacccacct?cagccttcca?aagtgctggg?attacaggtg?taagccacca?tgccaaggcc??97020
aaaacaacac?cacttcttaa?ctcacagttt?ggcgggtcca?aagcctgggt?ggtctggtct??97080
gggatctctg?cttaggagat?gtatttacat?aagtagacat?aattgaataa?ttgaacacat??97140
tgttgctgtt?attttgaaca?aactgtcatc?ttttagaata?agaaaaggaa?aatttttatt??97200
ttacctccac?ttactccttc?ttcaatgctt?tctttcttta?tgtagatcta?agtttctgaa??97260
ctacatattt?tccttctctc?taaagaattt?ctttaacatt?tcttgcaagt?cagagctatt??97320
agcaacaact?tccttcaatt?ttagtttgag?aagtctttat?tttgtcttca?attttgaagg??97380
ataatttcac?tgggtaaaga?attctaggga?tttttttcct?gtcaacaggt?catggcactg??97440
tcttcttgct?tgcatggttt?ctgaggaaaa?gtgaaaggca?attctttttt?tgttgttgtt??97500
cctttataga?agtcccttgg?gcttctttaa?aactttttgt?ttttctcttt?tttttgaaat??97560
ggagtctcac?tctgtcaccc?aggctggagt?gcagtggcgt?gatcttgact?cactgcaacc??97620
tccacctcct?gggttcaagc?aattctcctg?ccacagactc?ctgagtagct?gggattacag??97680
gtgcccgcca?acatgcctga?ctaatttttg?tatttttagt?aaagacaggg?tttcaccatg??97740
ttggccagtc?tggtcttgaa?ctcctgacct?caagtgacct?gcccacctct?gcctcccaaa??97800
gtgctgggat?tacaggtgtg?aaccaccgtg?cctgacctaa?aattttttat?ctttgatttt??97860
ctgtagttta?caaattatat?gcctatgtgt?tggggttttg?gggcatatat?cctacatggt??97920
gttctgcgag?cttcctggat?ctgtggtttg?gtgtttgacc?ttaatttgga?aaacatttca??97980
gtctttcttg?cttcaagtat?ttctgatgtt?actttcctct?ttcttctcct?tctgatattt??98040
ctattatgca?tctagtatac?cttttgtact?tatcccacaa?tccttggata?ttctgttatg??98100
gtttttcttt?tctagtcttt?gctctcttag?cttgtcagtt?ttgtaggttt?ctattgatat??98160
gctcttgaac?tcagagattc?tttcctcagc?ggggtcctgt?ctactaataa?gcctgtcaaa??98220
ggcattcttc?atttctctca?cagtgttttt?gatctctagc?atttattttt?tgttcttagg??98280
atttccatct?ctctgcttat?attgctctta?catgctctct?actttattca?ttagagcttt??98340
tagcatatta?atcatagtta?ttttaaattc?ccagtctgat?aatttcaaca?tccctgtcat??98400
gtctgcttct?gacttgtgtt?ttcaaactat?gtttttgcct?tttagtatgc?cttgtaattt??98460
ttcttgatag?ccagatatga?tgtatcaggt?aaaaagactt?tgtctaaata?agtctttagt??98520
aatgtgatgg?taaggtgtga?ggagagggaa?agcattctac?agtcctatga?ttaggtctca??98580
gtcttttagt?gagcctattc?ctctggacta?agaacttcac?aagtgctttt?cagtcccctc??98640
ttccttaggt?gggacataat?ggctagaact?gggtttagtt?gggtattcct?cttccccaag??98700
atcagttaga?ctctagtaaa?acccctggag?gttaggctct?ggttacatag?tttctcctga??98760
gggcacacct?tgtttagaaa?aacggagtac?tctggcatat?ttcaaaatgg?ttccttttcc??98820
tcttcctctg?ctgaaagaat?gagagatttt?ttttcctcca?atatttactg?agagatcctg??98880
gttgagcttc?tggaggtaaa?acacacaaaa?ctgtgggggc?tcacctgaag?gtgtttgggg??98940
tttttttttg?tctaattttt?gttgttgttg?ttgttggaga?cagagtctca?ctctgtcgcc??99000
caggctggag?tgcaatggcg?tgatctcggc?tcactgcaac?ctccgtctcc?taggttcaag??99060
tgattctcgt?gcctcagcct?cccgagtagc?tgggattaca?ggcacccgcc?atcatgcctg??99120
gctaattttt?gtatttttgt?agagatgggg?tttcaccatg?ttggccaggc?tggtcctgaa??99180
ctcctgacct?caggtgatcc?gaccacctcg?gcctcccaaa?gtgctgggat?tacaggcatg??99240
agcccacgtg?tggcctaatt?tttttttatt?gtgatccaaa?tacacatagc?ataaaactta??99300
acattttaat?catgtttaag?tatgcagttc?agtggtatga?aatacatttc?taatgttgtg??99360
tatccatgtc?tgccctccat?ctccataact?ctcttcatct?tgtcaaacaa?caactctata??99420
cccattaagt?gtatgtttgt?tatatttagt?tggtttattg?tgttgtctaa?gtcctctgtg??99480
tcttatcttt?tgtataattg?ttctatccat?tattgactgt?tagtgaagtc?tccaactact??99540
attatagaac?tgtctatttc?tacctttaat?tttgtcagtt?tttgcttcat?atatattgac??99600
gatcttattg?gatgcataaa?tgtttataat?tgttatattt?ttattttaaa?aatataatta??99660
taaaacaaat?gtttataatt?gttatatata?ttttgctgta?tttaaatttt?tattaatata??99720
ttattctttg?cctcttgtaa?gtttctttct?gatttaaagt?ttattttgtc?tgacattagt??99780
atagccacct?ttattctctt?tgggttacta?tttgtataaa?gtatcttttt?ctatcttcac??99840
tttccattta?tttgtgtctt?tggatctaaa?gtgagtctct?tttagtatgt?aattagatca??99900
tgtttttaaa?aaatccattc?tgccaacttg?tttttttgtt?gagagtttaa?ttcaatttaa???99960
agtaattact?gataaagagg?gacttgtgtg?tatcattttg?ctatttgttt?tcaatatgcc??100020
ttacagcttt?ttcattcctc?atttcctgaa?ctagtgtctt?attttgcatt?taatttttca??100080
tagtggaaca?tttaagttct?ttccccattt?tcttttgtat?atattctata?gctattttcc??100140
ttatggttac?catgaggatt?acatttagca?tcctaaagtt?aacttcagta?atgcacaaag??100200
aactccactc?ctttaatagc?ttcccacccc?tttcagttgt?tgatgtcaca?gaattacatt??100260
tttgtacatt?atatgcccca?aaacataaat?gaataattat?tttaaatgat?cagtctcttc??100320
aattatgtag?aaaacaaact?gtggagttac?aacccaaagt?tacaatacta?ctagcttttg??100380
ggctactaaa?ttttaaaaac?gtattaatct?cttaaaaacg?tagaaaacaa?aacaagttac??100440
aaactgttat?tacaataaca?cttaattgtc?catgtattta?cctttgttga?gatctttatt??100500
tcttcttaga?gctttgactg?tcctttcatt?ttaccctaca?gggctccttt?aggtatttct??100560
tgtctttctt?tcttttcttt?tctttctttt?ttttaaggcg?tgggcatttt?ttggaagaaa??100620
gtcctggtgg?taattaactt?tgtttttgat?tgtctgggaa?tgtcttaatt?tctcccttat??100680
cttcgaagga?cgcttttgct?gaatagaaga?ctcttggttg?acgggttttt?ttttgttttt??100740
ttaatatttt?gaatgtattg?gcccactgcc?ttctgacctc?taaattttca?gatgagaaat??100800
ctgctcatga?tcttattgaa?gatgtcttgt?atgtgattag?ttgcttctct?cactgctttc??100860
aagttttgtg?tctttcactt?ttcaaaagtg?attatatttg?tctcagtgtg?tatctcttta??100920
agtttatctt?acttggagtt?tgttgagctt?cttggatgtt?tatattcatg?tcttttatca??100980
aatttggaaa?gtttttaacc?attatttctt?caaatattct?ttctagtcct?ttctctctct??101040
cttcttcttc?agggacttcc?acaatgcatt?tattggttca?cttcttggtg?ttccacaagt??101100
cccttaggct?ctgttaactt?ttcttcaatc?ttttttcttt?ctgttcatca?gactcaataa??101160
tttccattgt?cttatcttca?agtctgctcc?ctgtttaatt?ctgcctttga?atccctctag??101220
tgattttttt?aaattttagt?tattgcagtt?ttcacctcca?gaatttcttt?ttggtatatt??101280
tttaggtttt?ctgtcacttt?actgttattt?ccattatttt?catacatcaa?ttacttgact??101340
ttatccacat?tttcctttag?ttctttgatt?atctttagag?ttgtttaaaa?atctttgtgt??101400
aggatatctg?ccattaggtc?tttttcaggg?acagtttctc?ttgatatttt?ttcccccttg??101460
ggatgagcca?tgctttcctg?tttcttggta?tgcctttttg?ttgttattat?tggaaactag??101520
acctttgaat?ctaataatat?cacagctctg?gatatcaaat?tctccctctt?ccccagggtt??101580
ttctgggttt?tgttgttgtt?tttgtttttt?attgttgtag?gctgtctcta?tgccaaggat??101640
cagcctgagg?tgcaaactta?aggtcttccc?agatcttttc?tgagcctgtg?cctttcccta??101700
aggcatgcac?agtcactttc?taattttcct?tttataggca?gttgcttttg?aatgtcctag??101760
tatttaatgt?ctggctgtca?aggtggtgga?gggtgggtgg?agaaaaaaat?aaagttgggg??101820
gaggaaaggg?caatagccct?ttaaatccac?tggaagtcac?ttcaactgga?gtgggagggg??101880
cttgcaatga?cggggagagg?tgcaacaatg?actgcctacc?tcttccatca?gaagcagcaa??101940
ttggtgatca?gagcacagat?ccctgatatc?tcagacaggg?tcctttttgc?ccacccttgt??102000
tcccacaagt?tgtacgcagg?ttcttcagga?gcatgtgcac?aacaactgtc?tgccacaggt??102060
tttgaggctg?ggggacaggc?agctgtgcta?agagctgaaa?ctgaaattaa?cctcagttta??102120
ccatccaagc?cttcctctgg?tatttacaag?ccttcagtag?actccagagt?tctaaaatag??102180
ttacattctg?acagattctg?ccagtgtaat?gatagtctag?gtggggctac?agatagttgg??102240
tacttcctac?tctgccgtct?ctccagaatc?ctcttctccc?tagagttttt?aactcccaga??102300
ccggtccagt?ctgagtttct?agcaattcat?caattacagt?tcaggttttt?ctagcctggc??102360
actggttccc?acagtggttt?ccacttgtga?gtctccatct?gtttgtctct?ccagtcttag??102420
gggcagcagt?ttgccctgtg?ttctcacttc?tcttatggat?ccaagaatag?ttgttgatct??102480
tccagtctgt?tcagctttat?ttatttattt?atttttgaga?tggagtctca?ctctgtcaca??102540
aggctggagt?gcagtggcac?gatctcggct?cactgcaacc?tctgcctccc?tggttcaagc??102600
gattctcctg?cctcagcctc?ctgagtagct?gggactacag?gcgtgcacga?ccatgcctgg??102660
ctaatttttg?tatttttagt?agagacggag?tttcaccatg?ttggccagga?tggtcttgat??102720
ctcttgacct?tgtgatccac?ccacctcggc?ctcccaaagt?gctgggatta?taggcatgag??102780
ccactgcgcc?cagcctgttc?agctttttac?ttgtttctag?gaccaagtgg?ttatttccaa??102840
gctccttaca?tgcagaaatg?gccaattttt?tttcctaatt?tttcaacaat?taacttgtac??102900
tgccttaata?atcataataa?tcaaaataat?tttttaaaaa?aagttattgc?agagaagtaa??102960
tgatgggatc?tctcaggtca?attcctgatc?tcagtggacc?atggtggcta?ctctgcctga??103020
catttattgt?cttatctcca?atacctactg?tgtatgtctc?tataatgtat?tttctcactt??103080
gattgcttaa?atccttgaaa?tgttcccaaa?tcatctgtga?aggaaataac?ttacagtcaa??103140
ggacccctgt?ttaattctaa?tatactgttg?tgggtttttt?ttctttagaa?cttggagaat??103200
ctggtggctc?aaaataccac?tggccctgtc?ttttgcccaa?ggctctacca?cctgatggct??103260
tacgtctgta?tattaatggg?agatgggcag?aaatgtggcc?tcttcctgaa?cacagccttg??103320
cggctctctg?aaacacaggg?gaatatactg?gagaaatgct?ggctgaacat?gaacaaagta??103380
tgtatcatca?gctagcaaac?cggggtggcg?atgctcaccc?atataaagaa?gcccagaagc??103440
ctactgcctg?gttaggtttc?accaggctgc?cattaacaaa?atatcttaga?ctgggtcatt??103500
gatgaacaat?agaaacctac?tgctcagttt?tggaagctgg?aagtccaaga?tcaaggctct??103560
ggagattcgc?tgtctggtga?gggtccgttc?ctcacagatg?gtgccttttg?ctgtgtcctc??103620
acatgtcaaa?aggatggaaa?aagaaaattt?gctccctcca?gcccttttat?gagggcagag??103680
ccctcatgac?ctaattacct?tccaaaggcc?caactcttaa?taccattacc?ttgggggtta??103740
attttcaaca?tatgaatttc?aggagatgcc?aacattcaga?ccatagcagt?caccataggc??103800
ctttctggat?tcttaccaga?aagggtgaca?tgtccatagt?tcaggattgt?gagcttcctc??103860
ttccccttta?agttctcatg?gtctctctcc?ctcatccaaa?tcccccttag?catgccctct??103920
ctctgccctt?ctttgtggcc?actttccact?ttgtgttaca?tctgtctgcg?tgtctttcct??103980
ctccttgaga?atgtgaactc?tttgaaagca?aaaaccacac?ttagtgccta?gcacagagcc??104040
ctatactcag?ttttgttgaa?taagtgaatg?aatgtatgag?tatatgtgtg?tatttaaaga??104100
gggctgtgtc?agtatcctag?tttggacagc?aagattcgtt?tttgtctatg?ggttcacatg??104160
gtttttacca?aagatgtttt?gccttgtttg?atattggact?aaccttgatt?acaaaagtca??104220
agaagcacta?atgatttctt?tgttctgttt?ctttcctctc?aggaatcatg?gtactcaacc??104280
tctgagttaa?aagaagacca?atggcttcag?acgatcttga?gtctcccatc?atgggaaaaa??104340
attgtagcag?gcagggtaaa?cattcaggat?cttcaaaaaa?acaaattcct?gatgagagct??104400
aataccgtgg?acaatcattt?ctaa?????????????????????????????????????????104424
Claims (5)
1, be used to predict the primer of diabetes B susceptibility, the special primer that is used for pcr amplification that described primer designs for the sequence based on Figure 1B or Figure 1A, described primer designs at the SNP site R shown in the figure, and length is 18-46 Nucleotide.
2, primer as claimed in claim 1, it comprises one group a kind of sequence that is selected from SEQ ID NO:1-26 composition.
3, primer as claimed in claim 2, it is the single-basic extension primer with the sequence shown in the SEQ ID NO:25 SEQ IDNO:26.
4, be used to predict the test kit of diabetes B susceptibility, it comprises each described primer as claim 1-3.
5, the SAC gene is used for predicting the application of the diagnostic reagent of diabetes B susceptibility in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031369758A CN1548553A (en) | 2003-05-21 | 2003-05-21 | Reagent kit and primer for predicting susceptibility of type-II diabetes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031369758A CN1548553A (en) | 2003-05-21 | 2003-05-21 | Reagent kit and primer for predicting susceptibility of type-II diabetes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1548553A true CN1548553A (en) | 2004-11-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031369758A Pending CN1548553A (en) | 2003-05-21 | 2003-05-21 | Reagent kit and primer for predicting susceptibility of type-II diabetes |
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| CN (1) | CN1548553A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101238222B (en) * | 2005-06-20 | 2013-04-10 | 解码遗传学私营有限责任公司 | Genetic variants in the TCF7L2 gene as diagnostic markers for risk of type 2 diabetes mellitus |
| CN106978474A (en) * | 2016-08-17 | 2017-07-25 | 上海易瑞生物科技有限公司 | A kind of diabetes B tumor susceptibility gene detection and genotyping kit and its application |
-
2003
- 2003-05-21 CN CNA031369758A patent/CN1548553A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101238222B (en) * | 2005-06-20 | 2013-04-10 | 解码遗传学私营有限责任公司 | Genetic variants in the TCF7L2 gene as diagnostic markers for risk of type 2 diabetes mellitus |
| CN106978474A (en) * | 2016-08-17 | 2017-07-25 | 上海易瑞生物科技有限公司 | A kind of diabetes B tumor susceptibility gene detection and genotyping kit and its application |
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