摘要： 目的·通过整合不孕症遗传因素大数据，挖掘突变规律及相关致病基因。方法·根据全球蛋白资源数据库（Universal Protein Resource，Uniprot）蛋白类别对搜集的人类不孕症致病基因进行分类，统计分析临床病例中每类基因的突变频数。针对功能异常的氧化还原酶这一重要致病因素，进行功能和通路分析，观察通路的相关情况。于小鼠基因数据库（Mouse Genome Informatics，MGI）获取人类类固醇激素生成通路的小鼠同源基因及致病信息，寻找规律并结合基因互作分析评估其中的潜在基因。结果·不孕症致病基因里氧化还原酶类基因突变最常见，可能最易发生突变；其聚集于类固醇激素生成通路，发现潜在相关突变基因，并发现此通路醛酮还原酶家族1成员C3（aldo-keto reductase family 1 member C3，
AKR1C3）是其中最可能的人类不孕症的潜在致病基因。结论·主要产生类固醇激素的氧化还原酶类致病基因在不孕症中突变最常见，可能包括
AKR1C3。
关键词: 不孕症, 大数据, 氧化还原酶, 类固醇激素通路, AKR1C3 Abstract: Objective·To mine regular patterns of mutation and associated causative genes through integrating big data from the perspective of genetic factors in infertility.
Methods·A classification of causative genes collected in human infertility according to the protein category in the Universal Protein Resource (Uniprot) and statistics of mutation frequency in each kind of genes in clinical cases were made. The function and pathway of oxidoreductase with abnormal function, an important pathogenic factor, were analyzed, and related information was investigated. The mouse ortholog genes and pathogenic information of human steroid hormone biosynthesis were acquired from Mouse Genome Informatics (MGI) in order to evaluate potential genes after finding out regularity and analysis of gene interaction.
Results·It's commonest for oxidoreductase genes to be mutated in infertility-causative genes. The genes that mutated most easily seemed possibly to focus on the steroid hormone biosynthesis pathway, and, furthermore, potential and related mutation genes were found. Aldo-keto reductase family 1 member C3 (AKR1C3), an oxidoreductase, was considered as a candidate gene bringing about human infertility most probably after analyzing this pathway.
Conclusion·It's commonest for oxidoreductase-causative genes, which are mainly responsible for generating steroid hormone, to be mutated in infertility, and these genes maybe include AKR1C3.
Key words: infertility, big data, oxidoreductase, steroid hormone biosynthesis, AKR1C3 PDF全文下载地址:
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