• PMID: 25739334
• Gene Name: UBR2
• Condition: Non-obstructive azoospermia
• Association: The study 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 fre
• Population size: 1466
• Population details: 1466 (757 NOA patients, 709 fertile males)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1, USP26, BRDT and MTHFR
• Other associated phenotypes: Non-obstructive azoospermia

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

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.

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. FAU - Li, Zesong AU - Li Z AD - 1] Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China [2] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [3] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. FAU - Huang, Yi AU - Huang Y AD - 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. FAU - Li, Honggang AU - Li H AD - Family Planning Research Institute/The Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Hu, Jingchu AU - Hu J AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Liu, Xiao AU - Liu X AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Jiang, Tao AU - Jiang T AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Sun, Guangqing AU - Sun G AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Tang, Aifa AU - Tang A AD - 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. FAU - Sun, Xiaojuan AU - Sun X AD - 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. FAU - Qian, Weiping AU - Qian W AD - The Center of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China. FAU - Zeng, Yong AU - Zeng Y AD - Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, China. FAU - Xie, Jun AU - Xie J AD - Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China. FAU - Zhao, Wei AU - Zhao W AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Xu, Yu AU - Xu Y AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - He, Tingting AU - He T AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Dong, Chengliang AU - Dong C AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Liu, Qunlong AU - Liu Q AD - The Center of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China. FAU - Mou, Lisha AU - Mou L AD - 1] Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China [2] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [3] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. FAU - Lu, Jingxiao AU - Lu J AD - 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. FAU - Lin, Zheguang AU - Lin Z AD - Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China. FAU - Wu, Song AU - Wu S AD - 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. FAU - Gao, Shengjie AU - Gao S AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Guo, Guangwu AU - Guo G AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Feng, Qiang AU - Feng Q AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Li, Yingrui AU - Li Y AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Zhang, Xiuqing AU - Zhang X AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Wang, Jun AU - Wang J AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Yang, Huanming AU - Yang H AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Wang, Jian AU - Wang J AD - BGI-Shenzhen, Shenzhen 518083, China. FAU - Xiong, Chengliang AU - Xiong C AD - Family Planning Research Institute/The Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Cai, Zhiming AU - Cai Z AD - 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.