title: Examination of disease-based selection, demographic history and population structure in European Y-chromosome haplogroup I.
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.
authors.affiliation: Laboratory of Genomic Diversity, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. sezginef@mail.nih.gov
authors.forename: Efe
authors.initials: E
authors.lastname: Sezgin
authors.forename: Alyssa
authors.initials: A
authors.lastname: Drosdak
authors.forename: Carl
authors.initials: C
authors.lastname: McIntosh
authors.forename: Bailey
authors.initials: B
authors.lastname: Kessing
authors.forename: James A
authors.initials: JA
authors.lastname: Lautenberger
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: John P
authors.initials: JP
authors.lastname: Phair
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Troyer
authors.forename: Michael W
authors.initials: MW
authors.lastname: Smith
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000483:Alleles; D051927:CD24 Antigen / Q000235:genetics; D041322:Chromosomes, Human, Y; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D018450:Disease Progression; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; D015778:Minor Histocompatibility Antigens; C492034:DDX3Y protein, human; D053487:DEAD-box RNA Helicases