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

Abstract

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.

• Authors: 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
• Journal: Molecular human reproduction (Mol Hum Reprod) Vol. 20 Issue 9 Pg. 836-43 (Sep 2014) ISSN: 1460-2407 [Electronic] England
• PMID: 24935076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• BPY2 protein, human
• DAZ1 protein, human
• Deleted in Azoospermia 1 Protein
• Proteins
• RNA-Binding Proteins

Topics

• Adult
• Asian People
• Azoospermia (genetics, pathology, physiopathology)
• Case-Control Studies
• China
• Chromosomes, Human, Y
• Cohort Studies
• Deleted in Azoospermia 1 Protein
• Gene Deletion
• Gene Dosage
• Gene Duplication
• Genetic Association Studies
• Genetic Loci
• Humans
• Infertility, Male (etiology)
• Male
• Multigene Family
• Proteins (genetics, metabolism)
• RNA-Binding Proteins (genetics, metabolism)
• Retrospective Studies
• Spermatogenesis