title: DAZ gene copies: evidence of Y chromosome evolution.
abstract: The DAZ gene, a contributing factor in infertility, lies on the human Y chromosome's AZFc region, whose deletion is a common cause of spermatogenic failure. Y chromosome binary polymorphisms on the non-recombining Y (NRY) region, believed to be a single occurrence on an evolutionary scale, were typed in a sample of fertile and infertile men with known DAZ backgrounds. The Y single-nucleotide polymorphisms (Y-SNPs) with low mutation rates are currently well characterized and permit the construction of a unique phylogeny of haplogroups. DAZ haplotypes were defined using single-nucleotide variant (SNV)/sequence tagged-site (STS) markers to distinguish between the four copies of the gene. The variation of 10 Y chromosome short tandem repeat (STRs) was used to determine the coalescence age of DAZ haplotypes in a comparable time frame similar to that of SNP haplogroups. An association between DAZ haplotypes and Y chromosome haplogroups was found, and our data show that the DAZ gene is not under selective constraints and its evolution depends only on the mutation rate. The same variants were common to fertile and infertile men, although partial DAZ deletions occurred only in infertile men, suggesting that those should only be used as a tool for infertility diagnosis when analysed in combination with haplogroup determinations.
authors.affiliation: Laboratory of Human Genetics, University of Madeira, Campus la Penteada, 9000-390 Funchal, Madeira, Portugal. atgf@uma.pt
authors.forename: Ana Teresa
authors.initials: AT
authors.lastname: Fernandes
authors.forename: Susana
authors.initials: S
authors.lastname: Fernandes
authors.forename: Rita
authors.initials: R
authors.lastname: Gonçalves
authors.forename: Rosália
authors.initials: R
authors.lastname: Sá
authors.forename: Paula
authors.initials: P
authors.lastname: Costa
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rosa
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferrás
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
authors.forename: António
authors.initials: A
authors.lastname: Brehm
authors.forename: Alberto
authors.initials: A
authors.lastname: Barros
mesh_terms: D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D000075364:Deleted in Azoospermia 1 Protein; D019143:Evolution, Molecular; D017353:Gene Deletion; D018628:Gene Dosage; D056426:Genetic Loci; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D029589:Seminal Plasma Proteins / Q000235:genetics
chemical_list: C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D016601:RNA-Binding Proteins; D029589:Seminal Plasma Proteins