Samudra Pal1, Pranab Paladhi1, Saurav Dutta1, Gunja Bose2, Papiya Ghosh3, Ratna Chattopadhyay2, Baidyanath Chakravarty2, Indranil Saha4, Sujay Ghosh5. 1. Cytogenetics & Genomics Research Unit, Department of Zoology, University of Calcutta, Taraknath-Palit-Siksha-Prangan, Ballygunge Science College Campus, 35 Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. 2. Institute of Reproductive Medicine (IRM), HB-36/A/3 1st Cross Rd Bidhannagar, Sector III, Bidhannagar, Kolkata, West Bengal, 700106, India. 3. Department of Zoology, Bijoy Krishna Girls' College (Affiliated to University of Calcutta), Howrah, West Bengal, India. 4. Genome-The Fertility Centre, 61-E, Sarat Bose Road, Kolkata, West Bengal, 700025, India. 5. Cytogenetics & Genomics Research Unit, Department of Zoology, University of Calcutta, Taraknath-Palit-Siksha-Prangan, Ballygunge Science College Campus, 35 Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. sgzoo@caluniv.ac.in.
Abstract
PURPOSE: Genetic etiology of idiopathic male infertility is enigmatic owing to involvement of multiple gene regulatory networks in spermatogenesis process. Any change in optimal function of the transcription factors involved in this process owing to polymorphisms/mutations may increase the risk of infertility. We investigated polymorphisms/mutations of spermatogenic transcription regulators TAF7 and RFX2 and analysed their association with incidence of azoospermia among the men from West Bengal, India. METHODS: Genotyping was carried by Sanger's dideoxy sequencing of 130 azoospermic men who were detected negative in Y chromosome microdeletion screening and 140 healthy controls. Association study was done by suitable statistical methods. In silico analysis was performed to infer the intuitive damaging effects of detected variants at transcripts and protein level. RESULTS: We found significant association of TAF7 C16T (MW827584 G > A), RFX2 562delT (MZ560629delA), rs11547633 A > C, rs17606721 A > G, MW827583 C > T, and MZ379836 C > T variants with the incidence of azoospermia. In silico analysis predicted that the variants either alter the natural splice junctions of the transcript or cause probable damage in the structure of proteins of respective genes. CONCLUSION: Polymorphisms/mutations of TAF7 and RFX2 genes increase risk of male infertility in Bengali population. The novel variants may be used as markers for male infertility screening in ART practise.
PURPOSE: Genetic etiology of idiopathic male infertility is enigmatic owing to involvement of multiple gene regulatory networks in spermatogenesis process. Any change in optimal function of the transcription factors involved in this process owing to polymorphisms/mutations may increase the risk of infertility. We investigated polymorphisms/mutations of spermatogenic transcription regulators TAF7 and RFX2 and analysed their association with incidence of azoospermia among the men from West Bengal, India. METHODS: Genotyping was carried by Sanger's dideoxy sequencing of 130 azoospermic men who were detected negative in Y chromosome microdeletion screening and 140 healthy controls. Association study was done by suitable statistical methods. In silico analysis was performed to infer the intuitive damaging effects of detected variants at transcripts and protein level. RESULTS: We found significant association of TAF7 C16T (MW827584 G > A), RFX2 562delT (MZ560629delA), rs11547633 A > C, rs17606721 A > G, MW827583 C > T, and MZ379836 C > T variants with the incidence of azoospermia. In silico analysis predicted that the variants either alter the natural splice junctions of the transcript or cause probable damage in the structure of proteins of respective genes. CONCLUSION: Polymorphisms/mutations of TAF7 and RFX2 genes increase risk of male infertility in Bengali population. The novel variants may be used as markers for male infertility screening in ART practise.