Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics.
Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics.
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DOI：
10.1371/journal.pone.0181604
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Goldstein DB
中科院分区：
文献类型：
--
作者：
Gussow AB;Copeland BR;Dhindsa RS;Wang Q;Petrovski S;Majoros WH;Allen AS;Goldstein DB
人们普遍认为，发生在蛋白质编码区之外的基因突变在人类疾病中发挥着关键作用。尽管达成了这一共识，但我们还不能分辨出非编码序列的哪些部分在人类疾病的背景下是重要的。在这里，我们提出了猎户座，这是一种检测非编码基因组中没有变异的区域的方法，这表明这些区域对突变是不能容忍的，并受到人类谱系中净化选择的影响。我们发现猎户座与已知的不耐受区域以及可能存在致病变异的区域高度相关。这种方法提供了一种机制来识别人类非编码基因组中的致病变异，并将在患者基因组的诊断解释和使用全基因组序列的大型病例对照研究中立即有用。
There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease. Here, we present Orion, an approach that detects regions of the non-coding genome that are depleted of variation, suggesting that the regions are intolerant of mutations and subject to purifying selection in the human lineage. We show that Orion is highly correlated with known intolerant regions as well as regions that harbor putatively pathogenic variation. This approach provides a mechanism to identify pathogenic variation in the human non-coding genome and will have immediate utility in the diagnostic interpretation of patient genomes and in large case control studies using whole-genome sequences.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
9.8
作者：
通讯作者：
--
影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
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
DOI：
10.1073/pnas.0812824106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Kryukov, Gregory V.;Shpunt, Alexander;Sunyaev, Shamil R.
通讯作者：
Sunyaev, Shamil R.