title: Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs).
abstract: Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Zesong
authors.initials: Z
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Su
authors.affiliation: Shool of bioscience &bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Family Planning Research Institute/The Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|College of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing, 100094, China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Luo
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zeng
authors.affiliation: BGI-Wuhan, Wuhan, China.
authors.forename: Huaiqian
authors.initials: H
authors.lastname: Xu
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Mou
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jingchu
authors.initials: J
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Weiping
authors.initials: W
authors.lastname: Qian
authors.affiliation: The Center of Reproductive Medicine, Shenzhen Zhongshan Urological Hospital, Shenzhen 518045, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Family Planning Research Institute/The Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Chengliang
authors.initials: C
authors.lastname: Xiong
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
mesh_terms: D000465:Algorithms; D053713:Azoospermia / Q000235:genetics*; D016022:Case-Control Studies; D041322:Chromosomes, Human, Y / Q000235:genetics*; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D017384:Sequence Deletion; D016324:Sequence Tagged Sites