Objectives: To better understand the effect of admixture on long range linkage disequilibrium (LD), we characterized extended LD in gene-rich regions of an African-American population. Methods: Approximately 290 cM of chromosomes 1, 3, 6, 11–17, 20 and 22 were scanned using 109 polymorphic microsatellite markers spaced an average of 3 cM apart. Disequilibrium between loci (D′) was based on maximum-likelihood estimates of haplotype frequencies computed for 200 unrelated African Americans. Results: Mean D′ values were highest on chromosomes 6p23–p21.3 (D′ = 0.33) and 15p22.2–p25.3 (D′ = 0.34), and lowest on chromosome 12p11.2–q14 (D′ = 0.21). Overall, the variance in LD among chromosomes accounted for approximately two-thirds of the total LD variance. Of the 434 locus pairs spaced between 0.3 and 38.7 cM apart, there was no detectable correlation between LD and recombination distance and a weak negative correlation between LD and physical distance (rs = –0.12; p = 0.031). For the 192 intrachromosomal locus pairs where allele frequency data were available from the Centre d’Etude du Polymorphisme humain (CEPH), we found a statistically significant positive correlation between LD and the allelic frequency differences (δ) between the African-American study population and Caucasian reference CEPH population (rs = 0.53; p < 0.0001). The correlation between LD and both recombination and physical distance was markedly increased for locus pairs with high δ levels. Conclusions: Our results suggest that recent Caucasian admixture maintains a high level of long range LD in African Americans on a genomic scale, and selected markers with large African American/Caucasian δ levels may be useful in association studies.

Keywords:
Allelic association, Haplotype, Microsatellite
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© 2002 S. Karger AG, Basel
2002
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