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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 infertilemen 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 groupwas 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.

Original languageEnglish (US)
Article numbergau043
Pages (from-to)836-843
Number of pages8
JournalMolecular Human Reproduction
Volume20
Issue number9
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Azoospermia
Gene Dosage
Y Chromosome
Genes
Spermatogenesis
Chromosomes, Human, Y
Oligospermia
Gene Deletion
Statistical Factor Analysis
Reproduction
Testis
Control Groups
Population

Keywords

  • AZFc
  • Copy number alteration
  • Spermatogenic impairment
  • Y chromosome haplogroup

ASJC Scopus subject areas

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Cell Biology

Cite this

Gene copy number alterations in the azoospermia-associated AZFc region and their effect on spermatogenic impairment. / Lu, Chuncheng; Jiang, Jie; Zhang, Ruyang; Wang, Ying; Xu, Miaofei; Qin, Yufeng; Lin, Yuan; Guo, Xuejiang; Ni, Bixian; Zhao, Yang; Diao, Nancy; Chen, Feng; Shen, Hongbing; Sha, Jiahao; Xia, Yankai; Hu, Zhibin; Wang, Xinru.

In: Molecular Human Reproduction, Vol. 20, No. 9, gau043, 01.01.2014, p. 836-843.

Research output: Contribution to journalArticle

Lu, C, Jiang, J, Zhang, R, Wang, Y, Xu, M, Qin, Y, Lin, Y, Guo, X, Ni, B, Zhao, Y, Diao, N, Chen, F, Shen, H, Sha, J, Xia, Y, Hu, Z & Wang, X 2014, 'Gene copy number alterations in the azoospermia-associated AZFc region and their effect on spermatogenic impairment', Molecular Human Reproduction, vol. 20, no. 9, gau043, pp. 836-843. https://doi.org/10.1093/molehr/gau043
Lu, Chuncheng ; Jiang, Jie ; Zhang, Ruyang ; Wang, Ying ; Xu, Miaofei ; Qin, Yufeng ; Lin, Yuan ; Guo, Xuejiang ; Ni, Bixian ; Zhao, Yang ; Diao, Nancy ; Chen, Feng ; Shen, Hongbing ; Sha, Jiahao ; Xia, Yankai ; Hu, Zhibin ; Wang, Xinru. / Gene copy number alterations in the azoospermia-associated AZFc region and their effect on spermatogenic impairment. In: Molecular Human Reproduction. 2014 ; Vol. 20, No. 9. pp. 836-843.
@article{67e5ef3db7b34b5eb60852e1c8b8de07,
title = "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 infertilemen 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 groupwas 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.",
keywords = "AZFc, Copy number alteration, Spermatogenic impairment, Y chromosome haplogroup",
author = "Chuncheng Lu and Jie Jiang and Ruyang Zhang and Ying Wang and Miaofei Xu and Yufeng Qin and Yuan Lin and Xuejiang Guo and Bixian Ni and Yang Zhao and Nancy Diao and Feng Chen and Hongbing Shen and Jiahao Sha and Yankai Xia and Zhibin Hu and Xinru Wang",
year = "2014",
month = "1",
day = "1",
doi = "10.1093/molehr/gau043",
language = "English (US)",
volume = "20",
pages = "836--843",
journal = "Molecular Human Reproduction",
issn = "1360-9947",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Gene copy number alterations in the azoospermia-associated AZFc region and their effect on spermatogenic impairment

AU - Lu, Chuncheng

AU - Jiang, Jie

AU - Zhang, Ruyang

AU - Wang, Ying

AU - Xu, Miaofei

AU - Qin, Yufeng

AU - Lin, Yuan

AU - Guo, Xuejiang

AU - Ni, Bixian

AU - Zhao, Yang

AU - Diao, Nancy

AU - Chen, Feng

AU - Shen, Hongbing

AU - Sha, Jiahao

AU - Xia, Yankai

AU - Hu, Zhibin

AU - Wang, Xinru

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 infertilemen 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 groupwas 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.

AB - 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 infertilemen 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 groupwas 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.

KW - AZFc

KW - Copy number alteration

KW - Spermatogenic impairment

KW - Y chromosome haplogroup

UR - http://www.scopus.com/inward/record.url?scp=84906058191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906058191&partnerID=8YFLogxK

U2 - 10.1093/molehr/gau043

DO - 10.1093/molehr/gau043

M3 - Article

VL - 20

SP - 836

EP - 843

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

SN - 1360-9947

IS - 9

M1 - gau043

ER -