The Human Genome Linkage Disequilibrium Intensity And Application

Linkage disequilibrium (LD) is nonrandom association between different loci. It is part of the genome information on population level. Existence of LD between markers and suspect loci is the prerequisite for association analysis and fine mapping of disease suspect genes.According to discrete changes of LD in local region of human genome, loci in the small region could be divided into different haplotype blocks. Only few SNPs are needed to represent most haplotype diversity in each block. These haplotype tagging SNPs (htSNPs) could be used as markers in association study. Lower cost and higher statistic power are expected in this approach.Three continental populations had been chosen in Hapmap poject for high-quality genotyping. But, efficiency of using htSNPs from these populations in other ones still needs to be validated.Linkage disequilibrium was affected by mutation, recombination, drift, admixture as well as a series of other population demographic and random factors. Wang et al proved that block-liked structure could be generated naturally in a population with limited size. Zhang et al shows that population demographic events and recombination hotspot could effect the procedure of haplotype block genesis. McVean et al inferred that recombination rate is greatly different even in locally genome region. Research work about Finland and other isolated populations shows that special population history could produce special LD pattern in it. Understanding more about mechanism and procedure of LD reinforcement and decay will accelerate the using of LD in genetics research work.For exploring LD pattern in human genome, we chose more than 20,000 loci from human chromosome 21 and typed in 368 individual samples. These samples were come from five Asian populations (Han, Zhuang, Miao, Uyghur, Wa) and three other populations (European, African American, Samoan). Our result shows that LD patterns of non-African populations were largely affected by common bottleneck events in their history, which have contributed a lot to the conservative LD patterns among non-African populations.By comparing correlations between average LD extending length and genetic distance among different populations, we indicated that LD reinforcement generated by information loss of historical recombination events is the leading mode of theworldwide change of LD patterns among different populations in the last 100,000 years.Confident evidence from frequency relationship among Han, Uyghur and European populations clearly shows admixture of West and East in Uyghur population. By the same approach, we find no evidence of admixture between Samoa aborigines and Europeans.From pattern of LD decay in Samoan, we inferred that serious bottleneck events that contributed more to LD in Samoan were happened about 4500 years before. Result of LD sharing between Samoan and other population reinforced previous opinion, that seriously and enduringly common bottleneck events is mainly case of conservation of LD pattern among non-Afro populationsBy a direct and efficacious approach, our research compared the universality of tagging SNPs, which have warranted the using of tagging SNPs between East Asian populations without the remarkable loss of statistical power. Strategies for tagging SNP selection in association study are also discussed in this paper.