title: Microhomology-mediated microduplication in the y chromosomal azoospermia factor a region in a male with mild asthenozoospermia.
abstract: Y chromosomal azoospermia factor (AZF) regions AZFa, AZFb and AZFc represent hotspots for copy number variations (CNVs) in the human genome; yet the number of reports of AZFa-linked duplications remains limited. Nonallelic homologous recombination has been proposed as the underlying mechanism of CNVs in AZF regions. In this study, we identified a hitherto unreported microduplication in the AZFa region in a Japanese male individual. The 629,812-bp duplication contained 22 of 46 exons of USP9Y, encoding the putative fine tuner of spermatogenesis, together with all exons of 3 other genes/pseudogenes. The breakpoints of the duplication resided in the DNA/TcMar-Tigger repeat and nonrepeat sequences, respectively, and were associated with a 2-bp microhomology, but not with short nucleotide stretches. The breakpoint-flanking regions were not enriched with GC content, palindromes, or noncanonical DNA structures. Semen analysis of the individual revealed a normal sperm concentration and mildly reduced sperm motility. The paternal DNA sample of the individual was not available for genetic analysis. The results indicate that CNVs in AZF regions can be generated by microhomology-mediated break-induced replication in the absence of known rearrangement-inducing DNA features. AZFa-linked microduplications likely permit production of a normal amount of sperm, although the precise clinical consequences of these CNVs await further investigation.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Momori
authors.initials: M
authors.lastname: Katsumi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kazuki
authors.initials: K
authors.lastname: Saito
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Kobori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okada
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Saito
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.forename: Mami
authors.initials: M
authors.lastname: Miyado
mesh_terms: D000328:Adult; D053627:Asthenozoospermia / Q000235:genetics* / Q000473:pathology; D056905:Chromosome Breakpoints; D041322:Chromosomes, Human, Y / Q000235:genetics*; D056915:DNA Copy Number Variations; D020440:Gene Duplication; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D011544:Pseudogenes; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: D015778:Minor Histocompatibility Antigens; C481724:USP9Y protein, human; D043222:Ubiquitin Thiolesterase