人类中KATNAL1基因序列变异与无精子症之间不存在关联。
Lack of association of KATNAL1 gene sequence variants and azoospermia in humans.
作者信息
Fedick Anastasia M, Eckert Kyle, Thompson Katharine, Forman Eric J, Devkota Batsal, Treff Nathan R, Taylor Deanne, Scott Richard T
机构信息
Department of Microbiology and Molecular Genetics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, 08854-5635, USA,
出版信息
J Assist Reprod Genet. 2014 Aug;31(8):1065-71. doi: 10.1007/s10815-014-0269-1. Epub 2014 Jun 10.
PURPOSE
A recent experiment indicated that a loss of function mutation in the murine Katnal1 gene resulted in male factor infertility due to premature exfoliation of spermatids. This study investigated the relevance of this gene to infertility in humans.
METHODS
Multiple methods of genetic analysis were employed to investigate whether mutations in human KATNAL1 have a causative role in male infertility. This was a genetic association study, which included DNA samples from 105 men with non-obstructive azoospermia (NOA) and 242 anonymous sperm donor controls. 28 commercially available TaqMan SNP assays were used to haplotype samples from both groups and genetically tag regions of interest across the entire gene. AmpliSeq primers were then designed for identified regions so that targeted next-generation sequencing (NGS) could be used to identify causative variants.
RESULTS
Four SNPs in the 3'UTR demonstrated a putative association with NOA. The AmpliSeq primers designed for the 3'UTR provided 83 % coverage of the 7,202 basepairs within the regions of interest. Variant sites were analyzed against genetic models to identify sequence polymorphisms which associated with NOA. No variants met standard criteria for significance when tested between the groups.
CONCLUSIONS
This study suggests a lack of association of KATNAL1 gene sequence variants and azoospermia in humans.
目的
最近的一项实验表明，小鼠Katnal1基因的功能缺失突变会导致精子细胞过早脱落，从而引发男性因素不育。本研究调查了该基因与人类不育的相关性。
方法
采用多种遗传分析方法来研究人类KATNAL1基因的突变是否在男性不育中起致病作用。这是一项遗传关联研究，纳入了105名非梗阻性无精子症（NOA）男性的DNA样本以及242名匿名精子捐献者作为对照。使用28种市售的TaqMan SNP检测法对两组样本进行单倍型分析，并对整个基因的感兴趣区域进行基因标记。然后针对已识别区域设计扩增子测序引物，以便使用靶向新一代测序（NGS）来识别致病变体。
结果
3'非翻译区（3'UTR）的四个单核苷酸多态性（SNP）显示出与NOA的假定关联。为3'UTR设计的扩增子测序引物覆盖了感兴趣区域内7202个碱基对的83%。根据遗传模型对变异位点进行分析，以识别与NOA相关的序列多态性。在两组之间进行测试时，没有变异符合显著意义的标准。
结论
本研究表明，KATNAL1基因序列变异与人类无精子症之间缺乏关联。
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