title: Haplotypes, mutations and male fertility: the story of the testis-specific ubiquitin protease USP26.
abstract: Recently, mutations in the X-linked ubiquitin protease 26 (USP26) gene have been proposed to be associated with male infertility. In particular a 371insACA, 494T>C and 1423C>T haplotype, which results in a T123-124ins, L165S and H475Y amino acid change respectively, has been reported to be associated with Sertoli cell-only syndrome (SCOS) and an absence of sperm in the ejaculate. Here, we demonstrate that two of these changes actually correspond to the ancestral sequence of the gene and that the USP26 haplotype is present in significant frequencies in sub-Saharan African and South and East Asian populations, including in individuals with known fertility. This indicates that the allele is not associated with infertility. The pattern of frequency distribution of the derived haplotype (371delACA, 494T), which is present at high frequencies in most non-African populations could be interpreted as either a result of migration followed by simple genetic drift or alternatively as positive selection acting on the derived alleles. The latter hypothesis seems likely, because there is evidence of strong positive selection acting on the USP26 gene.
authors.affiliation: Reproduction, Fertility and Populations, Institut Pasteur, 25 rue du Dr Roux, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Ravel
authors.forename: B
authors.initials: B
authors.lastname: El Houate
authors.forename: S
authors.initials: S
authors.lastname: Chantot
authors.forename: D
authors.initials: D
authors.lastname: Lourenço
authors.forename: A
authors.initials: A
authors.lastname: Dumaine
authors.forename: H
authors.initials: H
authors.lastname: Rouba
authors.forename: A
authors.initials: A
authors.lastname: Bandyopadahyay
authors.forename: U
authors.initials: U
authors.lastname: Radhakrishna
authors.forename: B
authors.initials: B
authors.lastname: Das
authors.forename: S
authors.initials: S
authors.lastname: Sengupta
authors.forename: J
authors.initials: J
authors.lastname: Mandelbaum
authors.forename: J P
authors.initials: JP
authors.lastname: Siffroi
authors.forename: K
authors.initials: K
authors.lastname: McElreavey
mesh_terms: D017954:Africa South of the Sahara; D001210:Asia, Southeastern; D003546:Cysteine Endopeptidases / Q000235:genetics*; D019143:Evolution, Molecular; D005298:Fertility / Q000235:genetics*; D005787:Gene Frequency; D040961:Genetic Drift; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D009154:Mutation; D013737:Testis / Q000201:enzymology*
chemical_list: C501866:USP26 protein, human; D003546:Cysteine Endopeptidases