Genetic variability and linkage disequilibrium within the HLA-DP region: analysis of 15 different populations

In order to understand the forces governing the evolution of the genetic di versity in the HLA-DP molecule, polymerase chain reaction (PCR)based method s were used to characterize genetic variation at the DPA1 and DPB1 loci enc oding this heterodimer on 2,807 chromosomes from 15 different populations i ncluding individuals of African, Asian, Amerindian, Indian and European ori gin. These ethnically diverse samples represent a variety of population sub structures and include small, isolated populations as well as larger, presu mably admired populations. Ten DPA1 and 39 DPB1 alleles were identified and observed on 87 distinct DP haplotypes, 34 of which were found to be in sig nificant positive linkage disequilibrium in at least one population. Some h aplotypes were found in all ethnic groups while others were confined to a s ingle ethnic group or population. Strong positive global linkage disequilib rium (W-n) between DPA1 and DPB1 was present in all 15 populations. The Afr ican populations displayed the lowest values of W-n whereas the Amerindian populations displayed near absolute disequilibrium. Analysis of the distrib ution of haplotypes using the normalized deviate of the Ewens-Watterson hom ozygosity statistic, F, suggests that DP haplotypes encoding the functional heterodimer are subject to much lower degrees of balancing selection than other loci within the HLA region. Finally, neighbor joining tree analyses d emonstrate the power of haplotype diversity for inferring the relationships between the different populations.