OBJECTIVE: To identify copy number variations (CNVs) as a hint toward genes relevant for spermatogenesis and related to male factor infertility. DESIGN: Analysis of genomic DNA with high resolution Illumina SNP arrays (HumanOmni1-Quad Bead Chip). Sanger sequencing of the CLCA4 gene in all patients of the study. Analysis of CLCA4 expression in various human tissue samples. SETTING: University department. PATIENT(S): A total of 39 infertile men with idiopathic infertility ranging from oligoasthenoteratozoospermia to azoospermia. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Copy number variations more than 10 kb. RESULT(S): We detected a heterozygous deletion including exons 4-9 of the CLCA4 gene in one man with cryptozoospermia, as well as a total of 149 CNVs not yet reported in various databases and carrying 200 protein coding genes in the 39 men. CONCLUSION(S): According to our results CLCA4 is apparently expressed in postmeiotic germ cells and somatic cells. We therefore conclude that CLCA4 might be functional during human spermatogenesis after meiosis, most likely as a modifier of CFTR gene expression. CLCA4 can thus be considered as a novel dominant germ line gene potentially causing male factor infertility if functionally disrupted. Our study demonstrates the power of DNA arrays to identify novel CNVs carrying candidate genes causing male factor infertility.
OBJECTIVE: To identify copy number variations (CNVs) as a hint toward genes relevant for spermatogenesis and related to male factor infertility. DESIGN: Analysis of genomic DNA with high resolution Illumina SNP arrays (HumanOmni1-Quad Bead Chip). Sanger sequencing of the CLCA4 gene in all patients of the study. Analysis of CLCA4 expression in various human tissue samples. SETTING: University department. PATIENT(S): A total of 39 infertilemen with idiopathic infertility ranging from oligoasthenoteratozoospermia to azoospermia. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Copy number variations more than 10 kb. RESULT(S): We detected a heterozygous deletion including exons 4-9 of the CLCA4 gene in one man with cryptozoospermia, as well as a total of 149 CNVs not yet reported in various databases and carrying 200 protein coding genes in the 39 men. CONCLUSION(S): According to our results CLCA4 is apparently expressed in postmeiotic germ cells and somatic cells. We therefore conclude that CLCA4 might be functional during human spermatogenesis after meiosis, most likely as a modifier of CFTR gene expression. CLCA4 can thus be considered as a novel dominant germ line gene potentially causing male factor infertility if functionally disrupted. Our study demonstrates the power of DNA arrays to identify novel CNVs carrying candidate genes causing male factor infertility.