• PMID: 19773397
• Gene Name: TSPY
• Condition: Spermatogenic efficiency, male infertility
• Association: Associated
• Mutation: TSPY copy number variation
• Population size: 284
• Population details: 284 (154 idiopathic infertile men, 130 normozoospermic controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: TSPY
• Other associated phenotypes: Spermatogenic efficiency, male infertility

TSPY1 copy number variation influences spermatogenesis and shows differences among Y lineages

Giachini C, Nuti F, Turner DJ, Laface I, Xue Y, Daguin F, Forti G, Tyler-Smith C, Krausz C.

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. FAU - Giachini, Claudia AU - Giachini C AD - Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence 50139, Italy. FAU - Nuti, Francesca AU - Nuti F FAU - Turner, Daniel J AU - Turner DJ FAU - Laface, Ilaria AU - Laface I FAU - Xue, Yali AU - Xue Y FAU - Daguin, Fabrice AU - Daguin F FAU - Forti, Gianni AU - Forti G FAU - Tyler-Smith, Chris AU - Tyler-Smith C