title: Identification and functional significance of SNPs underlying conserved haplotype frameworks across ethnic populations.
abstract: BACKGROUND
  The study of genetic variation will promote our understanding of the differential predisposition to common diseases and variation in drug responses of individuals and ethnic populations. Such genetic variation is intrinsically structured into blocks of haplotypes in populations. Therefore, a comprehensive haplotype map based on the most abundant form of genetic variation, single nucleotide polymorphisms, will be useful. At the present time, however, our knowledge of the similarities and differences of haplotype structure among different ancestral populations is still inadequate.
  
  
  METHODS
  To determine whether common underlying haplotype patterns existed across ethnic populations, we analyzed data derived from African and European Americans for twenty-two genes spanning a total of 516 kb and the HapMap ENCODE data across 500 kb on chromosome 2p16.3 from three major world populations.
  
  
  CONCLUSIONS
  We observed that strong pairwise linkage disequilibrium (LD) between SNPs selected from populations having African ancestry was highly conserved across other non-African populations. Common haplotypes described by these LD-selected SNPs demonstrated a simple evolutionary structure with up to three major frameworks, which were likely ancestral backgrounds upon which more recent mutations have been superimposed. Also, haplotype block boundaries defined in populations having African ancestry revealed completely concordant recombinant haplotypes across all populations, providing a consistent definition of block structure. Finally, a large fraction of regulatory polymorphisms described in the literature appeared to tag these conserved haplotype frameworks, strongly suggesting their significance for disease association and pharmacogenetic studies.
authors.affiliation: Division of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Ching
authors.initials: C
authors.lastname: Ouyang
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Krontiris
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D015870:Gene Expression; D014644:Genetic Variation / Q000502:physiology; D005828:Genetics, Population / Q000379:methods; D006239:Haplotypes / Q000502:physiology*; D006801:Humans; D015810:Linkage Disequilibrium; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D044382:Population Groups / Q000208:ethnology* / Q000235:genetics; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D014481:United States / Q000208:ethnology; D044465:White People / Q000235:genetics