Gene copy number alterations in the azoospermia-associated AZFc region and their effect on spermatogenic impairment.

نویسندگان

  • Chuncheng Lu
  • Jie Jiang
  • Ruyang Zhang
  • Ying Wang
  • Miaofei Xu
  • Yufeng Qin
  • Yuan Lin
  • Xuejiang Guo
  • Bixian Ni
  • Yang Zhao
  • Nancy Diao
  • Feng Chen
  • Hongbing Shen
  • Jiahao Sha
  • Yankai Xia
  • Zhibin Hu
  • Xinru Wang
چکیده

The azoospermia factor c (AZFc) region in the long arm of human Y chromosome is characterized by massive palindromes. It harbors eight multi-copy gene families that are expressed exclusively or predominantly in testis. To assess systematically the role of the AZFc region and these eight gene families in spermatogenesis, we conducted a comprehensive molecular analysis (including Y chromosome haplogrouping, AZFc deletion typing and gene copy quantification) in 654 idiopathic infertile men and 781 healthy controls in a Han Chinese population. The b2/b3 partial deletion (including both deletion-only and deletion-duplication) was consistently associated with spermatogenic impairment. In the subjects without partial AZFc deletions, a notable finding was that the frequency of DAZ and/or BPY2 copy number alterations in the infertile group was significantly higher than in the controls. Combined patterns of DAZ and/or BPY2 copy number abnormality were associated with spermatogenic impairment when compared with the pattern of all AZFc genes with common level copies. In addition, in Y chromosome haplogroup O1 (Y-hg O1), the frequency of copy number alterations of all eight gene families was significantly higher in the case group than that in the control group. Our findings indicate that the DAZ, BPY2 genes may be prominent players in spermatogenesis, and genomic rearrangements may be enriched in individuals belonging to Y-hg O1. Our findings emphasize the necessity of routine molecular analysis of AZFc structural variation during the workup of azoospermia and/or oligozoospermia, which may diminish the genetic risk of assisted reproduction.

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منابع مشابه

Association of partial AZFc region deletions with spermatogenic impairment and male infertility.

BACKGROUND Complete deletions of the AZFc region in distal Yq are the most frequent molecular genetic cause of severe male infertility. They are caused by intrachromosomal homologous recombination between amplicons--large, nearly identical repeats--and are found in 5-10% of cases of azoospermia and severe oligozoospermia. Homologous recombination may also generate different partial deletions of...

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Additional genomic duplications in AZFc underlie the b2/b3 deletion-associated risk of spermatogenic impairment in Han Chinese population.

The azoospermia factor c (AZFc) region on the Y chromosome is a genetically dynamic locus in the human genome. Numerous genomic rearrangements, including deletion, duplication and inversion, have been identified in AZFc. The complete deletion of AZFc can cause spermatogenic impairment. However, the roles of partial AZFc deletions (e.g. b2/b3 deletion) in spermatogenesis are controversial and va...

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Analysis of partial azoospermia factor c deletion and DAZ copy number in azoospermia and severe oligozoospermia.

Microdeletions of the azoospermia factor (AZF) regions in the Y chromosome are a well-known genetic cause of male infertility, resulting in impairment of spermatogenesis. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. We investigated partial deletion of AZFc region and DAZ copy number in a population of Iranian infertile men and normozoosp...

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بررسی حذف های کوچک کروموزوم Y در مردان نابارور مراجعه کننده به بیمارستان فاطمیه همدان با روش Multiplex PCR

Introduction & Objective: Male factor is the major cause of infertility in 20% of cases (WHO). There are known etiologies for 70% of cases .However, 30% of infertility cases are of idiopathic origin. The Y chromosome and micro deletion of the long arm of the Y chromosome (Yq) in three regions (AZFa, AZFb ,AZFc ) are associated with spermatogenic failure and is a major etiology for oligo and a...

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DAZ1/DAZ2 cluster deletion mediated by gr/gr recombination per se may not be sufficient for spermatogenesis impairment: a study of Chinese normozoospermic men.

AIM To explore the possible effect of the deleted in azoospermia (DAZ) copy cluster deletion on spermatogenesis in the Chinese population, the deletion of the azoospermia factor c (AZFc) region was analyzed in 346 normozoospermic men. METHODS Three DAZ single nucleotide variant loci and seven AZFc-specific sequence-tagged sites were examined with polymerase chain reaction (PCR)-restriction fr...

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عنوان ژورنال:
  • Molecular human reproduction

دوره 20 9  شماره 

صفحات  -

تاریخ انتشار 2014