Examination of disease-based selection, demographic history and population structure in European Y-chromosome haplogroup i

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Abstract

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. © 2010 The Japan Society of Human Genetics. All rights reserved.

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Sezgin, E., Drosdak, A., McIntosh, C., Kessing, B., Lautenberger, J. A., Goedert, J. J., … O’Brien, S. J. (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. https://doi.org/10.1038/jhg.2010.77

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