title: Intrachromosomal homologous recombination between inverted amplicons on opposing Y-chromosome arms.
abstract: Amplicons--large, nearly identical repeats in direct or inverted orientation--are abundant in the male-specific region of the human Y chromosome (MSY) and provide targets for intrachromosomal non-allelic homologous recombination (NAHR). Thus far, NAHR events resulting in deletions, duplications, inversions, or isodicentric chromosomes have been reported only for amplicon pairs located exclusively on the short arm (Yp) or the long arm (Yq). Here we report our finding of four men with Y chromosomes that evidently formed by intrachromosomal NAHR between inverted repeat pairs comprising one amplicon on Yp and one amplicon on Yq. In two men with spermatogenic failure, sister-chromatid crossing-over resulted in pseudoisoYp chromosome formation and loss of distal Yq. In two men with normal spermatogenesis, intrachromatid crossing-over generated pericentric inversions. These findings highlight the recombinogenic nature of the MSY, as intrachromosomal NAHR occurs for nearly all Y-chromosome amplicon pairs, even those located on opposing chromosome arms.
authors: Whitehead Institute, Howard Hughes Medical Institute, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: langej@mskcc.org.
authors: Julian
authors: J
authors: Lange
authors: Michiel J
authors: MJ
authors: Noordam
authors: Saskia K M
authors: SK
authors: van Daalen
authors: Helen
authors: H
authors: Skaletsky
authors: Brian A
authors: BA
authors: Clark
authors: Merryn V
authors: MV
authors: Macville
authors: David C
authors: DC
authors: Page
authors: Sjoerd
authors: S
authors: Repping
mesh_terms: D001483:Base Sequence; D002503:Centromere; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D059765:Homologous Recombination; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D055029:Inverted Repeat Sequences; D018404:Isochromosomes / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D012854:Sister Chromatid Exchange; D013091:Spermatogenesis
keywords: AZFc; DSB; FISH; Human Y chromosome; IR; MSY; Male infertility; NAHR; Non-allelic homologous recombination; PAR; STS; Structural variation; azoospermia factor c; double-strand break; fluorescence in situ hybridization; inverted repeat; male-specific region of the Y chromosome; non-allelic homologous recombination; pseudoautosomal region; sequence-tagged site
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