title: Natural positive selection and north-south genetic diversity in East Asia.
abstract: Recent reports have identified a north-south cline in genetic variation in East and South-East Asia, but these studies have not formally explored the basis of these clinical differences. Understanding the origins of these variations may provide valuable insights in tracking down the functional variants in genomic regions identified by genetic association studies. Here we investigate the genetic basis of these differences with genome-wide data from the HapMap, the Human Genome Diversity Project and the Singapore Genome Variation Project. We implemented four bioinformatic measures to discover genomic regions that are considerably differentiated either between two Han Chinese populations in the north and south of China, or across 22 populations in East and South-East Asia. These measures prioritized genomic stretches with: (i) regional differences in the allelic spectrum for SNPs common to the two Han Chinese populations; (ii) differential evidence of positive selection between the two populations as quantified by integrated haplotype score (iHS) and cross-population extended haplotype homozygosity (XP-EHH); (iii) significant correlation between allele frequencies and geographical latitudes of the 22 populations. We also explored the extent of linkage disequilibrium variations in these regions, which is important in combining genetic association studies from North and South Chinese. Two of the regions that emerged are found in HLA class I and II, suggesting that the HLA imputation panel from the HapMap may not be directly applicable to every Chinese sample. This has important implications to autoimmune studies that plan to impute the classical HLA alleles to fine map the SNP association signals.
authors.affiliation: Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.
authors.forename: Chen
authors.initials: C
authors.lastname: Suo
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Rick Th
authors.initials: RT
authors.lastname: Ong
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Jieming
authors.initials: J
authors.lastname: Chen
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Tay
authors.forename: Kar-Seng
authors.initials: KS
authors.lastname: Sim
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
mesh_terms: D000531:Altitude; D019295:Computational Biology; D005006:Ethnicity / Q000235:genetics; D005202:Asia, Eastern / Q000208:ethnology; D005787:Gene Frequency; D005805:Genes, MHC Class I; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D060148:HapMap Project; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic