CONTEXT: TSPY1 is a tandemly-repeated gene on the human Y chromosome forming an array of approximately 21-35 copies. The testicular expression pattern and the inferred function of the TSPY1 protein suggest possible involvement in spermatogenesis. However, data are scarce on TSPY1 copy number variation in different Y lineages and its role in spermatogenesis. OBJECTIVES: We sought to define: 1) the extent of TSPY1 copy number variation within and among Y chromosome haplogroups; and 2) the role of TSPY1 dosage in spermatogenic efficiency. MATERIALS AND METHODS: A total of 154 idiopathic infertile men and 130 normozoospermic controls from Central Italy were analyzed. We used a quantitative PCR assay to measure TSPY1 copy number and also defined Y haplogroups in all subjects. RESULTS: We provide evidence that TSPY1 copy number shows substantial variation among Y haplogroups and thus that population stratification does represent a potential bias in case-control association studies. We also found: 1) a significant positive correlation between TSPY1 copy number and sperm count (P < 0.001); 2) a significant difference in mean TSPY1 copy number between patients and controls (28.4 +/- 8.3 vs. 33.9 +/- 10.7; P < 0.001); and 3) a 1.5-fold increased risk of abnormal sperm parameters in men with less than 33 copies (P < 0.001). CONCLUSIONS: TSPY copy number variation significantly influences spermatogenic efficiency. Low TSPY1 copy number is a new risk factor for male infertility with potential clinical consequences.
CONTEXT: TSPY1 is a tandemly-repeated gene on the human Y chromosome forming an array of approximately 21-35 copies. The testicular expression pattern and the inferred function of the TSPY1 protein suggest possible involvement in spermatogenesis. However, data are scarce on TSPY1 copy number variation in different Y lineages and its role in spermatogenesis. OBJECTIVES: We sought to define: 1) the extent of TSPY1 copy number variation within and among Y chromosome haplogroups; and 2) the role of TSPY1 dosage in spermatogenic efficiency. MATERIALS AND METHODS: A total of 154 idiopathic infertile men and 130 normozoospermic controls from Central Italy were analyzed. We used a quantitative PCR assay to measure TSPY1 copy number and also defined Y haplogroups in all subjects. RESULTS: We provide evidence that TSPY1 copy number shows substantial variation among Y haplogroups and thus that population stratification does represent a potential bias in case-control association studies. We also found: 1) a significant positive correlation between TSPY1 copy number and sperm count (P < 0.001); 2) a significant difference in mean TSPY1 copy number between patients and controls (28.4 +/- 8.3 vs. 33.9 +/- 10.7; P < 0.001); and 3) a 1.5-fold increased risk of abnormal sperm parameters in men with less than 33 copies (P < 0.001). CONCLUSIONS: TSPY copy number variation significantly influences spermatogenic efficiency. Low TSPY1 copy number is a new risk factor for male infertility with potential clinical consequences.
Authors: Mark A Jobling; Iek Chi C Lo; Daniel J Turner; Georgina R Bowden; Andrew C Lee; Yali Xue; Denise Carvalho-Silva; Matthew E Hurles; Susan M Adams; Yuet Meng Chang; Thirsa Kraaijenbrink; Jürgen Henke; Ginevra Guanti; Brian McKeown; Roland A H van Oorschot; R John Mitchell; Peter de Knijff; Chris Tyler-Smith; Emma J Parkin Journal: Hum Mol Genet Date: 2006-12-22 Impact factor: 6.150
Authors: Z H Rosser; T Zerjal; M E Hurles; M Adojaan; D Alavantic; A Amorim; W Amos; M Armenteros; E Arroyo; G Barbujani; G Beckman; L Beckman; J Bertranpetit; E Bosch; D G Bradley; G Brede; G Cooper; H B Côrte-Real; P de Knijff; R Decorte; Y E Dubrova; O Evgrafov; A Gilissen; S Glisic; M Gölge; E W Hill; A Jeziorowska; L Kalaydjieva; M Kayser; T Kivisild; S A Kravchenko; A Krumina; V Kucinskas; J Lavinha; L A Livshits; P Malaspina; S Maria; K McElreavey; T A Meitinger; A V Mikelsaar; R J Mitchell; K Nafa; J Nicholson; S Nørby; A Pandya; J Parik; P C Patsalis; L Pereira; B Peterlin; G Pielberg; M J Prata; C Previderé; L Roewer; S Rootsi; D C Rubinsztein; J Saillard; F R Santos; G Stefanescu; B C Sykes; A Tolun; R Villems; C Tyler-Smith; M A Jobling Journal: Am J Hum Genet Date: 2000-11-09 Impact factor: 11.043
Authors: Yang Yang; Ti-Cheng Chang; Hiroshi Yasue; Arvind K Bharti; Ernest F Retzel; Wan-Sheng Liu Journal: BMC Genomics Date: 2011-01-07 Impact factor: 3.969