X Chromosome-Linked CNVs in Male Infertility: Discovery of Overall Duplication Load and Recurrent, Patient-Specific Gains with Potential Clinical Relevance
| Autor: | Chianese, Chiara, Gunning, Adam C., Giachini, Claudia, Daguin, Fabrice, Balercia, Giancarlo, Ars, Elisabet, Giacco, Deborah Lo, Ruiz-Castañé, Eduardo, Forti, Gianni, Krausz, Csilla, Universitat Autònoma de Barcelona |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Candidate gene Genetic Screens Heredity DNA Copy Number Variations Genetic Linkage Physiology Urology Gene Identification and Analysis lcsh:Medicine Locus (genetics) Biology Bioinformatics Male infertility Gene Duplication Gene duplication medicine Genetics Medicine and Health Sciences Reproductive Endocrinology Humans Clinical significance Copy-number variation lcsh:Science X chromosome Infertility Male Clinical Genetics Chromosomes Human X Multidisciplinary Endocrine Physiology lcsh:R Case-control study Biology and Life Sciences Computational Biology Human Genetics Genomics male infertiliy X chromosome-linked CNVs medicine.disease Genome Analysis Sex Linkage X-Linked Traits Infertility Case-Control Studies lcsh:Q Research Article |
| Zdroj: | PLoS One r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname PLoS ONE, Vol 9, Iss 6, p e97746 (2014) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. Materials and Methods: The copy number state of the five selected loci was analyzed by quantitative-PCR on a total of 276 idiopathic infertile patients and 327 controls in a conventional case-control setting (199 subjects belonged to the previous a-CGH study). For one interesting locus (intersecting DUP1A) additional 338 subjects were analyzed. Results and Discussion: All gains were confirmed as patient-specific and the difference in duplication load between patients and controls is significant (p = 1.65 x 10(-4)). Two of the CNVs are private variants, whereas 3 are found recurrently in patients and none of the controls. These CNVs include, or are in close proximity to, genes with testis-specific expression. DUP1A, mapping to the PAR1, is found at the highest frequency (1.4%) that was significantly different from controls (0%) (p = 0.047 after Bonferroni correction). Two mechanisms are proposed by which DUP1A may cause spermatogenic failure: i) by affecting the correct regulation of a gene with potential role in spermatogenesis; ii) by disturbing recombination between PAR1 regions during meiosis. This study allowed the identification of novel spermatogenesis candidate genes linked to the 5 CNVs and the discovery of the first recurrent, X-linked gain with potential clinical relevance. |
| Databáze: | OpenAIRE |
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