Significant Admixture Linkage Disequilibrium across 30 cM around the FY Locus in African Americans

• Published in: American journal of human genetics 2000-03, Vol.66 (3), p.969-978
• Main Authors: Lautenberger, James A., Stephens, J. Claiborne, O'Brien, Stephen J., Smith, Michael W.
• Format: Article
• Language: English
• Subjects: Admixture, linkage disequilibrium; Africa - ethnology; Alleles; Biological and medical sciences; Black or African American; Black People - genetics; Chromosome FY (Duffy); Chromosome Mapping - methods; Chromosomes, Human, Pair 1 - genetics; DNA-Binding Proteins - physiology; Duffy Blood-Group System - genetics; Erythroid-Specific DNA-Binding Factors; Europe - ethnology; Gene Frequency - genetics; General aspects. Genetic counseling; Genetic Markers - genetics; Genome scan; Haplotypes - genetics; Humans; Linkage Disequilibrium - genetics; Map(s)/mapping, admixture linkage disequilibrium; Medical genetics; Medical sciences; Models, Genetic; Polymorphism, Genetic - genetics; Population(s), African American; Promoter Regions, Genetic - genetics; Tandem Repeat Sequences - genetics; Transcription Factors - physiology; United States
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/302820

Scientists, to understand the importance of allelic polymorphisms on phenotypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chances of discovering functional gene-marker associations. One theoretically valid approach—mapping by admixture linkage disequilibrium (MALD), using recently admixed African Americans—is empirically evaluated here by measurement of marker associations with 15 short tandem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locus in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymorphism (−46T→C) disrupts the GA TA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of FY−/− in malaria infections. Analysis of linkage disequilibrium around the FY gene has indicated that there is strong and consistent linkage disequilibrium between FY and three flanking loci (D1S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-disequilibrium signals over a 30-cM region from −4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estimates of centimorgan limits, by MALD assessment in African American population-association analyses, of 5–10 cM.