title: Markers informative for ancestry demonstrate consistent megabase-length linkage disequilibrium in the African American population.
abstract: Admixture mapping is a potentially powerful tool for mapping complex genetic diseases. For application of this method, admixed individuals must have genomes composed of large segments derived intact from each founding population. Such segments are thought to be present in African Americans (AA) and should be demonstrable by examination of linkage disequilibrium (LD). Previous studies using a variety of polymorphic markers have variably reported long-range LD or rapid decay of LD. To further define the extent and characteristics of LD caused by admixture in the AA population, the current study utilized a set of 52 diallelic markers that were selected for large standard variances between putative representatives of the founder populations. LD was examined in over 250 marker-pairs, including linked markers from four different chromosomal regions and an equal number of matched unlinked comparisons. In the representative founder populations, strong LD was not observed for markers separated by more than 10 kb. In contrast, results indicated significant LD ( P<0.001, D'>0.3) in AA over large genomic segments exceeding 10 centiMorgans (cM) and 15 megabases (Mb). Only marginally significant LD was present between unlinked markers in this population, suggesting that choosing appropriate levels of significance for admixture mapping can minimize false positive results. The ability to detect LD for extended chromosomal segments in AA decayed not only as a function of the distance between markers, but also as a function of the standard variance of the markers. This examination of several genomic segments provides strong evidence that appropriate selection of informative markers is a crucial prerequisite for the application of admixture mapping to the AA population.
authors.affiliation: Rowe Program in Human Genetics, Departments of Biological Chemistry and Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616-8669, USA.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Collins-Schramm
authors.forename: Bill
authors.initials: B
authors.lastname: Chima
authors.forename: Darwin J
authors.initials: DJ
authors.lastname: Operario
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
mesh_terms: D001741:Black or African American; D044383:Black People / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D018703:Founder Effect; D005819:Genetic Markers; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D015810:Linkage Disequilibrium; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers