在线人类孟德尔遗传数据库的分析  

Analysis of online Mendelian inheritance in man

作　　者：吴静成 吕兴正 雷雅静 周婕[1] 周展[1] 陈枢青[1] 

机构地区：[1]浙江大学药学院/浙江省抗肿瘤药物临床前研究重点实验室,浙江杭州310058 [2]浙江大学计算机学院,浙江杭州310058 [3]杭州恩氏基因技术发展有限公司,浙江杭州310058

出　　处：《中国生化药物杂志》2017年第3期1-4,9,共5页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金项目(31501021);浙江省自然科学基金面上项目(LY15C06001)

摘　　要：目的 对在线人类孟德尔遗传数据库（OMIM）进行分析,加深对其的了解,为使用该数据库的研究人员提供参考。方法将OMIM数据库中19 414个遗传表型所对应的基因变异与1000 Genome Project,GO-ESP,ExAC等人类基因组或外显子组数据库进行比对,得到这些基因变异在各人群中的突变频率,对其进行统计学生物学分析。结果 19414个基因变异中,大约97.5%的基因变异的突变频率不高于1%,为罕见突变,320个基因变异的突变频率在3个数据库中均大于1%,为可信度较高的常见突变;19414个基因变异对应的表型中,127个表型为polymorphism,584个表型为susceptibility,而在320（1.6%）个常见突变对应的表型中有62个polymorphism,88个susceptibility,分别占48.8%和15.1%。结论OMIM中大部分基因变异为罕见突变;polymorphism和susceptibility在常见突变对应的表型中富集,在突变频率为10%~100%的变异中富集程度更高。Objective To analyze the data from Online Mendelian Inheritance in Man （OMIM） to understand more about it, and provide reference to researchers using this database.Methods 19414 mutations which have definite relevant phenotypes from OMIM were obtained, then these mutations with three databases （1000 Genome Project,GO-ESP,ExAC） which record the mutation frequency in different population were compared.Results Most of the phenotype-related mutations from OMIM are rare mutations whose mutation frequency is less than 1%：18866 in 1000 Genome Project, 18981 in GO-ESP, 18979 in ExAC.The number of mutation whose frequency is more than 1% is 548433435 in 1000 Genome Project, GO-ESP, ExAC, respectively.And there are 320 mutations whose frequency is more than 1% in all databases.In all phenotypes, there are 127 polymorphism phenotypes, 584 susceptibility phenotypes, while in 320 （ 1.6%） phenotypes with common mutations, there are 62 polymorphism phenotypes, 88 susceptibility phenotypes and occupies 48.8%, 15.1%, respectively.Conclusion Approximately 97.5% mutations in OMIM are rare mutations.Polymorphism and susceptibility enrich in common mutations, especially in the mutation whose frequency is more than 10%.

关 键 词：单基因遗传病 在线人类孟德尔遗传数据库 基因型与表型相互关系 罕见突变 基因频率 

分 类 号：R394.3[医药卫生—医学遗传学]