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在先天性双侧输精管缺如的印度男性中检测CFTR基因轻度变异多聚T、TG重复序列和M470V

The CFTR gene mild variants poly-T, TG repeats and M470V detection in Indian men with congenital bilateral absence of vas deferens.

作者信息

Gaikwad A, Khan S, Kadam S, Kadam K, Dighe V, Shah R, Kulkarni V, Kumaraswamy R, Gajbhiye R

机构信息

Department of Clinical Research, National Institute for Research in Reproductive Health, Mumbai, India.

Department of Anatomy and Developmental Biology, Monash University, VIC, 3800, Australia.

出版信息

Andrologia. 2018 Mar;50(2). doi: 10.1111/and.12858. Epub 2017 Aug 3.

Abstract

The aim of the study was to detect the frequency of the CFTR gene variants poly-T, TG repeats and c.1408A>G p.Met470Val (M470V) in Indian men with congenital bilateral absence of the vas deferens (CBAVD). Men diagnosed with CBAVD (n = 76), their female partners (n = 76) and healthy men from general population (n = 50) were recruited. Genomic DNA was isolated and the polymorphic regions of IVS9- c.1210-12T [5] and M470V were amplified using specific primers followed by Sanger's DNA sequencing. A statistically significant increase in the frequency of heterozygous IVS9- c.1210-12T [5] (39.4%) was observed in CBAVD men as compared to controls (14%). The allelic distribution of c.1210-12T [5], c.1210-12T [7] and c.1210-12T [9] in CBAVD men was 21%, 64.4% and 13% and that in healthy controls was 7%, 73% and 20% respectively. Longest TG repeat c.1210-34TG [13] was found in association with c.1210-12T [5] with an allelic frequency of 5.9% in CBAVD men. We found a significant association of c.1210-34TG [12]/c.1210-34TG [13] - c.1210-12[5] -V470 allele in CBAVD men. Twelve female partners harboured a heterozygous c.1210-12T [5] allele. The study emphasises the need to screen both partners for the polymorphisms M470V, poly-T, TG tract repeats in addition to population-specific known CFTR gene mutations.

摘要

本研究旨在检测先天性双侧输精管缺如(CBAVD)的印度男性中CFTR基因变异多聚T、TG重复序列以及c.1408A>G p.Met470Val(M470V)的频率。招募了被诊断为CBAVD的男性(n = 76)、他们的女性伴侣(n = 76)以及来自普通人群的健康男性(n = 50)。分离基因组DNA,使用特异性引物扩增IVS9 - c.1210 - 12T [5]和M470V的多态性区域,随后进行桑格DNA测序。与对照组(14%)相比,CBAVD男性中杂合子IVS9 - c.1210 - 12T [5](39.4%)的频率有统计学意义的增加。CBAVD男性中c.1210 - 12T [5]、c.1210 - 12T [7]和c.1210 - 12T [9]的等位基因分布分别为21%、64.4%和13%,而健康对照组中分别为7%、73%和20%。在CBAVD男性中发现最长的TG重复序列c.1210 - 34TG [13]与c.1210 - 12T [5]相关联,等位基因频率为5.9%。我们发现CBAVD男性中c.1210 - 34TG [12]/c.1210 - 34TG [13] - c.1210 - 12[5] -V470等位基因存在显著关联。12名女性伴侣携带杂合的c.1210 - 12T [5]等位基因。该研究强调除了特定人群已知的CFTR基因突变外,还需要对伴侣双方进行M470V、多聚T、TG序列重复多态性的筛查。

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