title: Haplotype diversity in 11 candidate genes across four populations.
abstract: Analysis of haplotypes based on multiple single-nucleotide polymorphisms (SNP) is becoming common for both candidate gene and fine-mapping studies. Before embarking on studies of haplotypes from genetically distinct populations, however, it is important to consider variation both in linkage disequilibrium (LD) and in haplotype frequencies within and across populations, as both vary. Such diversity will influence the choice of "tagging" SNPs for candidate gene or whole-genome association studies because some markers will not be polymorphic in all samples and some haplotypes will be poorly represented or completely absent. Here we analyze 11 genes, originally chosen as candidate genes for oral clefts, where multiple markers were genotyped on individuals from four populations. Estimated haplotype frequencies, measures of pairwise LD, and genetic diversity were computed for 135 European-Americans, 57 Chinese-Singaporeans, 45 Malay-Singaporeans, and 46 Indian-Singaporeans. Patterns of pairwise LD were compared across these four populations and haplotype frequencies were used to assess genetic variation. Although these populations are fairly similar in allele frequencies and overall patterns of LD, both haplotype frequencies and genetic diversity varied significantly across populations. Such haplotype diversity has implications for designing studies of association involving samples from genetically distinct populations.
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Beaty
authors.forename: M D
authors.initials: MD
authors.lastname: Fallin
authors.forename: J B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: I
authors.initials: I
authors.lastname: McIntosh
authors.forename: S S
authors.initials: SS
authors.lastname: Chong
authors.forename: R
authors.initials: R
authors.lastname: Ingersoll
authors.forename: X
authors.initials: X
authors.lastname: Sheng
authors.forename: R
authors.initials: R
authors.lastname: Chakraborty
authors.forename: A F
authors.initials: AF
authors.lastname: Scott
mesh_terms: D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007194:India / Q000208:ethnology; D015810:Linkage Disequilibrium; D008296:Malaysia / Q000208:ethnology; D008297:Male; D008396:Maryland; D020641:Polymorphism, Single Nucleotide; D012846:Singapore; D013624:Taiwan / Q000208:ethnology; D044465:White People / Q000235:genetics*