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。...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。展开更多
Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms thr...Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms three species, GLY0, GLY1, and GLY2. Here, we describe four independent families in which mutations in PANX1 cause familial or sporadic female infertility via a phenotype that we term “oocyte death.” The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.展开更多
上海交通大学医学院附属第九人民医院辅助生殖科匡延平研究组首次发现一种全新的遗传疾病,命名为“卵子死亡”,并就疾病的致病基因及作用机制进行挖掘。该研究成果以A pannexin 1channelopathy causes human oocyte death 为题于2019年3...上海交通大学医学院附属第九人民医院辅助生殖科匡延平研究组首次发现一种全新的遗传疾病,命名为“卵子死亡”,并就疾病的致病基因及作用机制进行挖掘。该研究成果以A pannexin 1channelopathy causes human oocyte death 为题于2019年3 月发表于国际著名学术期刊Sci Transl Med。展开更多
文摘目的·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。
文摘Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms three species, GLY0, GLY1, and GLY2. Here, we describe four independent families in which mutations in PANX1 cause familial or sporadic female infertility via a phenotype that we term “oocyte death.” The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.
