Dataset Information


DARC alleles and Duffy phenotypes in African Americans.

ABSTRACT: BACKGROUND:The DARC (Duffy blood group, chemokine receptor) gene encodes for a transmembrane glycoprotein that functions as a chemokine transporter, is a receptor for Plasmodium vivax and P. knowlesi, and expresses the Duffy blood group antigens (Fy). The Fy(a-b-) phenotype found in people of African descent is typically associated with a -67t>c mutation in the 5'-untranslated region (UTR), which prevents red blood cells being invaded by P. vivax and P. knowlesi. The aim of this study was to establish DARC allele frequencies in an African American blood donor cohort, determine a phylogenetic tree for DARC, and compare human and Neandertal DARC genes. STUDY DESIGN AND METHODS:The DARC nucleotide sequence of 54 African American blood donors was determined from genomic DNA. Heterozygous substitutions were resolved by sequencing of haplotype-specific amplifications. A phylogenetic tree for DARC was established using the neighbor-joining method with Pan troglodytes as root. RESULTS:A total of 108 haplotypes of the DARC gene could be unambiguously determined from nucleotide position -300 in the 5'?UTR to +300 in the 3' UTR. Eleven different alleles were found, including the clinically relevant FY*A, FY*B, FY*B-67C, FY*B298A, and FY*X alleles. All phenotype predictions based on genotypes matched the serologically determined phenotypes exactly: 52% Fy(a-b-), 28% Fy(a-b+), and 20% Fy(a+b-). CONCLUSIONS:The nucleotide sequencing approach using one amplicon is a practical genotyping method for DARC and allows the determination of haplotypes even in heterozygous constellations. We developed a phylogenetic tree for DARC alleles and postulated a distinct FY*B allele as ancestral for the extant DARC alleles in humans.

PROVIDER: S-EPMC3374024 | BioStudies |

REPOSITORIES: biostudies

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