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.
Institute of Reproductive Medicine (IRM), HB-36/A/3 1st Cross Rd Bidhannagar, Sector III, Bidhannagar, Kolkata, West Bengal, 700106, India.
J Assist Reprod Genet. 2021 Dec;38(12):3195-3212. doi: 10.1007/s10815-021-02352-5. Epub 2021 Nov 11.
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.
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.
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.
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.
由于参与精子发生过程的多个基因调控网络，特发性男性不育的遗传病因仍然扑朔迷离。由于多态性/突变，参与该过程的转录因子的最佳功能发生任何变化都可能增加不育的风险。我们研究了精子发生转录调节因子 TAF7 和 RFX2 的多态性/突变，并分析了它们与印度西孟加拉邦男性无精子症发生率的关系。
对 130 名无精子症患者（Y 染色体微缺失筛查呈阴性）和 140 名健康对照者进行 Sanger 双脱氧测序进行基因分型。通过适当的统计方法进行关联研究。通过计算分析推断检测到的转录本和蛋白质水平变异的直观破坏性影响。
我们发现 TAF7 C16T（MW827584 G> A）、RFX2 562delT（MZ560629delA）、rs11547633 A> C、rs17606721 A> G、MW827583 C> T 和 MZ379836 C> T 变体与无精子症的发生率显著相关。计算分析预测，这些变体要么改变转录本的天然剪接接头，要么导致相应基因蛋白结构的可能损伤。
TAF7 和 RFX2 基因的多态性/突变增加了孟加拉人群男性不育的风险。新的变体可作为 ART 实践中男性不育筛查的标记物。
