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首页> 外文期刊>Biology of Reproduction: Offical Journal of the Society for the Study of Reproduction >Identification of potentially damaging amino acid substitutions leading to human male infertility.
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Identification of potentially damaging amino acid substitutions leading to human male infertility.

机译:识别潜在的破坏性的氨基酸替换导致人类男性不育。

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摘要

There are a number of known genetic alterations found in men with nonobstructive azoospermia, or testicular failure, such as Y microdeletions and cytogenetic abnormalities. However, the etiology of nonobstructive azoospermia is unknown in the majority of men. The aim of this study was to investigate the possibility that unexplained cases of nonobstructive azoospermia are caused by nonsynonymous single-nucleotide polymorphisms (SNPs) in the coding regions of autosomal genes associated with sperm production and fertility. Using a candidate gene approach based on genetics of male infertility in mice, we resequenced nine autosomal genes from 78 infertile men displaying testicular failure using custom-made next-generation resequencing chips. Analysis of the data revealed several novel heterozygous nonsynonymous SNPs in four of nine sequenced genes in 14 of 78 infertile men. Eight SNPs in SBF1, three SNPs in LIMK2, two SNPs in LIPE, and one SNP in TBPL1 were identified. All of the novel mutations were in a heterozygous configuration, suggesting that they may be de novo mutations with dominant negative properties.
机译:有许多已知的基因改变发现在影像学上的男性精子缺乏,或睾丸衰竭,如Y微小缺失细胞遗传学异常。影像学上的精子缺乏是未知的大多数的男人。调查原因不明的可能性例影像学精子缺乏引起的产生的单核苷酸多态性(snp)在常染色体基因的编码区与精子的产生和生育能力。使用一个基于基因的候选基因的方法男性不育的老鼠,我们重新测序9从78年不育男性显示常染色体基因睾丸衰竭使用定制的新一代测序芯片。数据显示几个小说杂合的产生的单核苷酸多态性在四个九测序基因在14 78名不育男性。在LIMK2 SBF1,三个单核苷酸多态性,在时间两个snp,一个SNP TBPL1被确定。小说在一个杂合的突变配置,这表明他们可能是德突变与新生显性负属性。

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