Examination of Disease-Based Selection, Demographic History and Population Structure in European Y-Chromosome Haplogroup I
Journal of Human Genetics
AIDS progression, CD24L4/DDX3Y, Population growth, Population structure, Selection, Y chromosome
We attempted to refine the understanding of an association of Y-chromosomal haplogroup I (hg-I) with enhanced AIDS progression that had been previously reported. First, we compared the progression phenotype between hg-I and its phylogenetically closest haplogroup J. Then, we took a candidate gene approach resequencing DDX3Y, a crucial autoimmunity gene, in hg-I and other common European Y-chromosome haplogroups looking for functional variants. We extended the genetic analyses to CD24L4 and compared and contrasted the roles of disease-based selection, demographic history and population structure shaping the contemporary genetic landscape of hg-I chromosomes. Our results confirmed and refined the AIDS progression signal to hg-I, though no gene variant was identified that can explain the disease association. Molecular evolutionary and genetic analyses of the examined loci suggested a unique evolutionary history in hg-I, probably shaped by complex interactions of selection, demographic history and high geographical differentiation leading to the formation of distinct hg-I subhaplogroups that today are associated with HIV/AIDS onset. Clearly, further studies on Y-chromosome candidate loci sequencing to discover functional variants and discern the roles of evolutionary factors are warranted.
Sezgin, Efe; Alyssa Drosdak; Carl McIntosh; Bailey Kessing; J. A. Lautenberger; James J. Goedert; John Phair; Jennifer L. Troyer; Michael W. Smith; and Stephen J. O'Brien. 2010. "Examination of Disease-Based Selection, Demographic History and Population Structure in European Y-Chromosome Haplogroup I." Journal of Human Genetics 55, (9): 613-620. http://nsuworks.nova.edu/cnso_bio_facarticles/460