title: Identification of a Y chromosome haplogroup associated with reduced sperm counts.
abstract: In man, infertility is associated with microdeletions of specific regions of the long arm of the Y chromosome. This indicates that factors encoded by the Y chromosome are necessary for spermatogenesis. However, the majority of men with either idiopathic azoospermia or oligozoospermia have grossly intact Y chromosomes and the underlying causes of their infertility are unknown. We hypothesized that some of these individuals may carry other rearrangements or sequence variants on the non-recombining region of the Y chromosome that may be associated with reduced spermatogenesis. To test this hypothesis, we typed the Y chromosome in a group of Danish men with known sperm counts and compared the haplotype distribution with that of a group of unselected Danish males. We found that one class of Y chromosome, referred to as haplogroup 26+, was significantly overrepresented (27.9%; P < 0.001) in the group of men with either idiopathic oligozoospermia (defined as <20 x 10(6 )sperm/ml) or azoospermia compared to the control Danish male population (4.6%). This study defines, for the first time, a class of Y chromosome that is at risk for infertility in a European population. This observation suggests that selection may be indeed active on the Y chromosome, at least in the Danish population, raising the possibility that it could alter the pattern of Y chromosome haplotype distribution in the general population.
authors.affiliation: Immunogénétique Humaine, INSERM E021, Institut Pasteur, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Krausz
authors.forename: L
authors.initials: L
authors.lastname: Quintana-Murci
authors.forename: E
authors.initials: E
authors.lastname: Rajpert-De Meyts
authors.forename: N
authors.initials: N
authors.lastname: Jørgensen
authors.forename: M A
authors.initials: MA
authors.lastname: Jobling
authors.forename: Z H
authors.initials: ZH
authors.lastname: Rosser
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
authors.forename: K
authors.initials: K
authors.lastname: McElreavey
mesh_terms: D000483:Alleles; D019143:Evolution, Molecular; D005640:Follicle Stimulating Hormone / Q000097:blood; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D007265:Inhibins / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009845:Oligospermia / Q000235:genetics; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012661:Semen / Q000166:cytology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013076:Sperm Count; D014998:Y Chromosome / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D012738:Sex Hormone-Binding Globulin; C422364:inhibin B; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone