mirDNMR: a gene-centered database of background de novo mutation rates in human.
mirDNMR: a gene-centered database of background de novo mutation rates in human.
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mirDNMR：以基因为中心的人类背景从头突变率数据库。
DOI：
10.1093/nar/gkw1044
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发表时间：
2017-01-04
影响因子：
14.9
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Jiang Y;Li Z;Liu Z;Chen D;Wu W;Du Y;Ji L;Jin ZB;Li W;Wu J
新生生殖系突变（DNM）是最罕见的遗传变异，被证明会导致相当数量的散发性遗传疾病，如自闭症谱系障碍，癫痫性脑病，精神分裂症，先天性心脏病，1型糖尿病和听力损失。然而，很难准确地评估DNMs的原因，并从先证者中大量的DNMs中识别致病基因。解决这个问题的一种常用方法是鉴定含有比偶然预期显著更多DNM的基因，需要准确的背景DNM率（DNMR）。因此，在这项研究中，我们开发了一个新的数据库命名为mirDNMR收集基因为中心的背景DNMR从不同的方法和人口的变化数据。该数据库具有以下功能：（i）浏览和搜索由GC含量（DNMR-GC）、序列上下文（DNMR-SC）、多因子（DNMR-MF）和局部DNA甲基化水平（DNMR-DM）四种不同方法预测的每个基因的背景DNMR;（ii）在公开可用的数据库中搜索变体频率，包括ExAC、ESP 6500、UK 10 K，1000 G和dbSNP，以及（iii）使用三种统计方法（TADA、二项式和泊松检验）研究DNM负担以基于四种背景DNMR优先化候选基因。作为一个案例研究，我们成功地利用我们的数据库在候选基因的优先级为一个散发性的复杂疾病：智力残疾。总之，mirDNMR（https：//www.wzgenomics.cn/mirdnmr/）可广泛用于确定散发性遗传病的遗传基础。
De novo germline mutations (DNMs) are the rarest genetic variants proven to cause a considerable number of sporadic genetic diseases, such as autism spectrum disorders, epileptic encephalopathy, schizophrenia, congenital heart disease, type 1 diabetes, and hearing loss. However, it is difficult to accurately assess the cause of DNMs and identify disease-causing genes from the considerable number of DNMs in probands. A common method to this problem is to identify genes that harbor significantly more DNMs than expected by chance, with accurate background DNM rate (DNMR) required. Therefore, in this study, we developed a novel database named mirDNMR for the collection of gene-centered background DNMRs obtained from different methods and population variation data. The database has the following functions: (i) browse and search the background DNMRs of each gene predicted by four different methods, including GC content (DNMR-GC), sequence context (DNMR-SC), multiple factors (DNMR-MF) and local DNA methylation level (DNMR-DM); (ii) search variant frequencies in publicly available databases, including ExAC, ESP6500, UK10K, 1000G and dbSNP and (iii) investigate the DNM burden to prioritize candidate genes based on the four background DNMRs using three statistical methods (TADA, Binomial and Poisson test). As a case study, we successfully employed our database in candidate gene prioritization for a sporadic complex disease: intellectual disability. In conclusion, mirDNMR (https://www.wzgenomics.cn/mirdnmr/) can be widely used to identify the genetic basis of sporadic genetic diseases.
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影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
25
作者：
Chesi, Alessandra;Staahl, Brett T.;Jovicic, Ana;Couthouis, Julien;Fasolino, Maria;Raphael, Alya R.;Yamazaki, Tomohiro;Elias, Laura;Polak, Meraida;Kelly, Crystal;Williams, Kelly L.;Fifita, Jennifer A.;Maragakis, Nicholas J.;Nicholson, Garth A.;King, Oliver D.;Reed, Robin;Crabtree, Gerald R.;Blair, Ian P.;Glass, Jonathan D.;Gitler, Aaron D.
通讯作者：
Gitler, Aaron D.
1 型糖尿病患者 PHEX 新生突变
影响因子：
1.4
作者：
Fang, Chen;Li, Hui;Hu, Ji
通讯作者：
Hu, Ji
影响因子：
64.8
作者：
Sanders, Stephan J.;Murtha, Michael T.;Gupta, Abha R.;Murdoch, John D.;Raubeson, Melanie J.;Willsey, A. Jeremy;Ercan-Sencicek, A. Gulhan;DiLullo, Nicholas M.;Parikshak, Neelroop N.;Stein, Jason L.;Walker, Michael F.;Ober, Gordon T.;Teran, Nicole A.;Song, Youeun;El-Fishawy, Paul;Murtha, Ryan C.;Choi, Murim;Overton, John D.;Bjornson, Robert D.;Carriero, Nicholas J.;Meyer, Kyle A.;Bilguvar, Kaya;Mane, Shrikant M.;Sestan, Nenad;Lifton, Richard P.;Guenel, Murat;Roeder, Kathryn;Geschwind, Daniel H.;Devlin, Bernie;State, Matthew W.
通讯作者：
State, Matthew W.
影响因子：
4.5
作者：
Petrovski S;Wang Q;Heinzen EL;Allen AS;Goldstein DB
通讯作者：
Goldstein DB