Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals.
Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals.
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DOI：
10.1002/humu.22375
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发表时间：
2013-09
期刊：
影响因子：
3.9
通讯作者：
Jordan, Daniel M.
中科院分区：
文献类型：
--
作者：
Cassa, Christopher A.;Tong, Mark Y.;Jordan, Daniel M.
现在，从临床实验室订购临床解释的全基因组序列报告是负担得起的。这些报告的一个主要组成部分来自以前确定的致病性变异的知识库，包括研究文章，位点特异性和其他数据库。虽然已经确定了超过150，000种此类致病性变体，但其中许多最初是在受影响个体的小型队列研究中发现的，因此它们对无症状人群的适用性尚不清楚。我们分析了大量无症状个体（N= 1，092）的医学和科学文献中大量致病性变异的患病率，并在至少一个个体中发现了8.5%的这些致病性变异。在1000个基因组计划的平均个体中，先前鉴定的致病性变体在纯合形式中平均出现294次（σ= 25.5），在杂合形式中平均出现942次（σ = 68.2）。我们还发现，这些致病性变异中有许多是经常发生的：MAF >= 0.01的变异有3,744个（4.6%），MAF >= 0.05的变异有2,837个（3.5%）。这表明这些变体中的许多可能是错误的发现或具有比先前预期的更低的变异率。
It is now affordable to order clinically interpreted whole genome sequence reports from clinical laboratories. One major component of these reports is derived from the knowledge base of previously identified pathogenic variants, including research articles, locus specific and other databases. While over 150,000 such pathogenic variants have been identified, many of these were originally discovered in small cohort studies of affected individuals, so their applicability to asymptomatic populations is unclear. We analyzed the prevalence of a large set of pathogenic variants from the medical and scientific literature in a large set of asymptomatic individuals (N=1,092) and found 8.5% of these pathogenic variants in at least one individual. In the average individual in the 1000 Genomes Project, previously identified pathogenic variants occur on average 294 times (σ= 25.5) in homozygous form and 942 times (σ = 68.2) in heterozygous form. We also find that many of these pathogenic variants are frequently occurring: there are 3,744 variants with MAF >= 0.01 (4.6%) and 2,837 variants with MAF >= 0.05 (3.5%). This indicates that many of these variants may be erroneous findings or have lower penetrance than previously expected.
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影响因子：
5.8
作者：
Tong, Mark Y.;Cassa, Christopher A.;Kohane, Isaac S.
通讯作者：
Kohane, Isaac S.
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
DOI：
10.1038/gim.2011.68
发表时间：
2012-04
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1126/science.1217283
发表时间：
2012-05-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Keinan A;Clark AG
通讯作者：
Clark AG
影响因子：
3.9
作者：
Thompson, Bryony A.;Greenblatt, Marc S.;Vallee, Maxime P.;Herkert, Johanna C.;Tessereau, Chloe;Young, Erin L.;Adzhubey, Ivan A.;Li, Biao;Bell, Russell;Feng, Bingjian;Mooney, Sean D.;Radivojac, Predrag;Sunyaev, Shamil R.;Frebourg, Thierry;Hofstra, Robert M. W.;Sijmons, Rolf H.;Boucher, Ken;Thomas, Alun;Goldgar, David E.;Spurdle, Amanda B.;Tavtigian, Sean V.
通讯作者：
Tavtigian, Sean V.