Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia

Zesong Li; Yi Huang; Honggang Li; Jingchu Hu; Xiao Liu; Tao Jiang; Guangqing Sun; Aifa Tang; Xiaojuan Sun; Weiping Qian; Yong Zeng; Jun Xie; Wei Zhao; Yu Xu; Tingting He; Chengliang Dong; Qunlong Liu; Lisha Mou; Jingxiao Lu; Zheguang Lin; Song Wu; Shengjie Gao; Guangwu Guo; Qiang Feng; Yingrui Li; Xiuqing Zhang; Jun Wang; Huanming Yang; Jian Wang; Chengliang Xiong; Zhiming Cai; Yaoting Gui

doi:10.1038/srep08785

Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia

Zesong Li
, Yi Huang
, Honggang Li
, Jingchu Hu
, Xiao Liu
, Tao Jiang
, Guangqing Sun
, Aifa Tang
, Xiaojuan Sun
, Weiping Qian
, Yong Zeng
, Jun Xie
, Wei Zhao
, Yu Xu
, Tingting He
, Chengliang Dong
, Qunlong Liu
, Lisha Mou
, Jingxiao Lu
, Zheguang Lin

Song Wu, Shengjie Gao, Guangwu Guo, Qiang Feng, Yingrui Li, Xiuqing Zhang, Jun Wang, Huanming Yang, Jian Wang, Chengliang Xiong, Zhiming Cai, Yaoting Gui

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we successfully sequenced ∼650 infertility-related genes in 757 NOA patients and 709 fertile males. We evaluated the contributions of rare variants to the etiology of NOA by identifying individual genes showing nominal associations and testing the genetic burden of a given biological process as a whole. We found a significant excess of rare, non-silent variants in genes that are key epigenetic regulators of spermatogenesis, such as BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1 and USP26, in NOA patients (P = 5.5 × 10^-7), corresponding to a carrier frequency of 22.5% of patients and 13.7% of controls (P = 1.4 × 10^-5). An accumulation of low-frequency variants was also identified in additional epigenetic genes (BRDT and MTHFR). Our study suggested the potential associations of genetic defects in genes that are epigenetic regulators with spermatogenic failure in human.

Original language	English
Article number	8785
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep08785
State	Published - 2015
Externally published	Yes

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Li, Z., Huang, Y., Li, H., Hu, J., Liu, X., Jiang, T., Sun, G., Tang, A., Sun, X., Qian, W., Zeng, Y., Xie, J., Zhao, W., Xu, Y., He, T., Dong, C., Liu, Q., Mou, L., Lu, J., ... Gui, Y. (2015). Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia. Scientific Reports, 5, Article 8785. https://doi.org/10.1038/srep08785

@article{f51334f8bddf4b199cd9510e9d58f76d,

title = "Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia",

abstract = "Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we successfully sequenced ∼650 infertility-related genes in 757 NOA patients and 709 fertile males. We evaluated the contributions of rare variants to the etiology of NOA by identifying individual genes showing nominal associations and testing the genetic burden of a given biological process as a whole. We found a significant excess of rare, non-silent variants in genes that are key epigenetic regulators of spermatogenesis, such as BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1 and USP26, in NOA patients (P = 5.5 × 10-7), corresponding to a carrier frequency of 22.5\% of patients and 13.7\% of controls (P = 1.4 × 10-5). An accumulation of low-frequency variants was also identified in additional epigenetic genes (BRDT and MTHFR). Our study suggested the potential associations of genetic defects in genes that are epigenetic regulators with spermatogenic failure in human.",

author = "Zesong Li and Yi Huang and Honggang Li and Jingchu Hu and Xiao Liu and Tao Jiang and Guangqing Sun and Aifa Tang and Xiaojuan Sun and Weiping Qian and Yong Zeng and Jun Xie and Wei Zhao and Yu Xu and Tingting He and Chengliang Dong and Qunlong Liu and Lisha Mou and Jingxiao Lu and Zheguang Lin and Song Wu and Shengjie Gao and Guangwu Guo and Qiang Feng and Yingrui Li and Xiuqing Zhang and Jun Wang and Huanming Yang and Jian Wang and Chengliang Xiong and Zhiming Cai and Yaoting Gui",

year = "2015",

doi = "10.1038/srep08785",

language = "英语",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

}

Li, Z, Huang, Y, Li, H, Hu, J, Liu, X, Jiang, T, Sun, G, Tang, A, Sun, X, Qian, W, Zeng, Y, Xie, J, Zhao, W, Xu, Y, He, T, Dong, C, Liu, Q, Mou, L, Lu, J, Lin, Z, Wu, S, Gao, S, Guo, G, Feng, Q, Li, Y, Zhang, X, Wang, J, Yang, H, Wang, J, Xiong, C, Cai, Z & Gui, Y 2015, 'Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia', Scientific Reports, vol. 5, 8785. https://doi.org/10.1038/srep08785

TY - JOUR

T1 - Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia

AU - Li, Zesong

AU - Huang, Yi

AU - Li, Honggang

AU - Hu, Jingchu

AU - Liu, Xiao

AU - Jiang, Tao

AU - Sun, Guangqing

AU - Tang, Aifa

AU - Sun, Xiaojuan

AU - Qian, Weiping

AU - Zeng, Yong

AU - Xie, Jun

AU - Zhao, Wei

AU - Xu, Yu

AU - He, Tingting

AU - Dong, Chengliang

AU - Liu, Qunlong

AU - Mou, Lisha

AU - Lu, Jingxiao

AU - Lin, Zheguang

AU - Wu, Song

AU - Gao, Shengjie

AU - Guo, Guangwu

AU - Feng, Qiang

AU - Li, Yingrui

AU - Zhang, Xiuqing

AU - Wang, Jun

AU - Yang, Huanming

AU - Wang, Jian

AU - Xiong, Chengliang

AU - Cai, Zhiming

AU - Gui, Yaoting

PY - 2015

Y1 - 2015

N2 - Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we successfully sequenced ∼650 infertility-related genes in 757 NOA patients and 709 fertile males. We evaluated the contributions of rare variants to the etiology of NOA by identifying individual genes showing nominal associations and testing the genetic burden of a given biological process as a whole. We found a significant excess of rare, non-silent variants in genes that are key epigenetic regulators of spermatogenesis, such as BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1 and USP26, in NOA patients (P = 5.5 × 10-7), corresponding to a carrier frequency of 22.5% of patients and 13.7% of controls (P = 1.4 × 10-5). An accumulation of low-frequency variants was also identified in additional epigenetic genes (BRDT and MTHFR). Our study suggested the potential associations of genetic defects in genes that are epigenetic regulators with spermatogenic failure in human.

AB - Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we successfully sequenced ∼650 infertility-related genes in 757 NOA patients and 709 fertile males. We evaluated the contributions of rare variants to the etiology of NOA by identifying individual genes showing nominal associations and testing the genetic burden of a given biological process as a whole. We found a significant excess of rare, non-silent variants in genes that are key epigenetic regulators of spermatogenesis, such as BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1 and USP26, in NOA patients (P = 5.5 × 10-7), corresponding to a carrier frequency of 22.5% of patients and 13.7% of controls (P = 1.4 × 10-5). An accumulation of low-frequency variants was also identified in additional epigenetic genes (BRDT and MTHFR). Our study suggested the potential associations of genetic defects in genes that are epigenetic regulators with spermatogenic failure in human.

UR - https://www.scopus.com/pages/publications/84924362719

U2 - 10.1038/srep08785

DO - 10.1038/srep08785

M3 - 文章

C2 - 25739334

AN - SCOPUS:84924362719

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 8785

ER -

Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia

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