Single-Nucleotide Variant in Multiple Copies of a Deleted in Azoospermia (DAZ) Sequence – a Human Y Chromosome Quantitative Polymorphism

Abstract

The evolution of the deleted in azoospermia (DAZ) gene family supports prevalent theories on the origin and development of sex chromosomes and sexual dimorphism. The ancestral DAZL gene in human chromosome 3 is known to be involved in germline development of both males and females. The available phylogenetic data suggest that some time after the divergence of the New World and Old World monkey lineages, the DAZL gene, which is found in all mammals, was copied to the Y chromosome of an ancestor to the Old World monkeys, but not New World monkeys. In modern man, the Y-linked DAZ gene complex is located on the distal part of the q arm. It is thought that after being copied to the Y chromosome, and after the divergence of the human and great ape lineages, the DAZ gene in the former underwent internal rearrangements. This included tandem duplications as well as a T > C transition altering an MboI restriction enzyme site in a duplicated sequence. In this study, we report on the ratios of MboI–/MboI+ variant sequences in individuals from seven worldwide human populations (Basque, Benin, Egypt, Formosa, Kungurtug, Oman and Rwanda) in the DAZ complex. The ratio of PCR MboI– and MboI+ amplicons can be used to characterize individuals and populations. Our results show a nonrandom distribution of MboI–/MboI+ sequence ratios in all populations examined, as well as significant differences in ratios between populations when compared pairwise. The multiple ratios imply that there have been more than one recent reorganization events at this locus. Considering the dynamic nature of this locus and its involvement in male fertility, we investigated the extent and distribution of this polymorphism.

Integrated miRNA and mRNA expression profiling to identify mRNA targets of dysregulated miRNAs in non-obstructive azoospermia

“…Recent studies have identified a number of miRNAs that are significantly upregulated in human testis, spermatozoa, and seminal plasma 33 , and more than 80 genes have been identified as essential for male infertility in humans and mice 34 . Genes on the Y chromosome have been emphasized because of observed microdeletions in patients; in addition, genes such as DAZ and HSFY, which were also discovered in our results, have been examined as possible susceptibility genes for azoospermia 35 36 . Our comparative analysis revealed a large number of deregulated genes.…”

Genome-Wide Expression of Azoospermia Testes Demonstrates a Specific Profile and Implicates ART3 in Genetic Susceptibility

“…Thus far, more than 80 genes have been identified as essential for male infertility in humans and mice [ 3 ]. Genes on the Y chromosome were emphasized because of observed microdeletions in patients, and genes such as DAZ and HSFY were examined for possible susceptibility genes [ 28 , 29 ]. Recently, homozygous mutation of the aurora kinase C gene was identified in large-headed multiflagellar polyploid spermatozoa, a rare form of infertility, using homozygosity mapping [ 30 ].…”

Quantitative PCR technique for the identification of microrearrangements of the AZFc region

“…The limits of this technique have thus been demonstrated, although there may still be some qualitative interest [11]. Moreover, some of these SNVs (sY581 for example) proved to be useful polymorphisms for population genetic studies [23,24].…”