X chromosome-linked CNVs in male infertility: discovery of overall duplication load and recurrent, patient-specific gains with potential clinical relevance.

Introduction: Spermatogenesis is a highly complex process involving several thousand genes, only a minority of which have been studied in infertile men. In a previous study, we identified a number of Copy Number Variants (CNVs) by high-resolution array-Comparative Genomic Hybridization (a-CGH) analysis of the X chromosome, including 16 patient-specific X chromosome-linked gains. Of these, five gains (DUP1A, DUP5, DUP20, DUP26 and DUP40) were selected for further analysis to evaluate their clinical significance.

High resolution X chromosome-specific array-CGH detects new CNVs in infertile males.

Context: The role of CNVs in male infertility is poorly defined, and only those linked to the Y chromosome have been the object of extensive research. Although it has been predicted that the X chromosome is also enriched in spermatogenesis genes, no clinically relevant gene mutations have been identified so far.

Objectives: In order to advance our understanding of the role of X-linked genetic factors in male infertility, we applied high resolution X chromosome specific array-CGH in 199 men with different sperm count followed by the analysis of selected, patient-specific deletions in large groups of cases and normozoospermic controls.

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

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.