Mutation rates and fitness consequences of mosaic chromosomal alterations in blood
Mutation rates and fitness consequences of mosaic chromosomal alterations in blood
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血液中镶嵌染色体改变的突变率和适应性后果
DOI：
10.1101/2022.05.07.491016
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Watson C
中科院分区：
文献类型：
--
作者：
Watson C
嵌合染色体改变（mCA）在癌症中很常见，并且可能在诊断前几十年出现。定量了解这些事件发生的速率及其功能后果，可以改善癌症风险预测和我们对体细胞进化的理解。使用来自大约50万名英国生物库参与者血液的mCA克隆大小估计值，我们估计了获得性获得、丢失和拷贝中性杂合性丢失事件的突变率和适应性后果。大多数mCA具有中度到高度的适应性效应，但发生率较低，比等效拟合的单核苷酸变异少十倍以上。值得注意的例外是X和Y的嵌合丢失，我们估计其突变率比常染色体mCA高约1,000倍。虽然大多数mCA的患病率随年龄增长的方式是一致的恒定增长率，一些mCA表现出不同的行为，这表明他们的健身可能取决于遗传变异，外在因素或健身效果的分布。
Mosaic chromosomal alterations (mCAs) are common in cancers and can arise decades before diagnosis. A quantitative understanding of the rate at which these events occur, and their functional consequences, could improve cancer risk prediction and our understanding of somatic evolution. Using mCA clone size estimates from the blood of approximately 500,000 UK Biobank participants, we estimate mutation rates and fitness consequences of acquired gain, loss and copy-neutral loss of heterozygosity events. Most mCAs have moderate to high fitness effects but occur at a low rate, being more than tenfold less common than equivalently fit single-nucleotide variants. Notable exceptions are mosaic loss of X and Y, which we estimate have roughly 1,000-fold higher mutation rates than autosomal mCAs. Although the way in which most mCAs increase in prevalence with age is consistent with constant growth rates, some mCAs exhibit different behavior, suggesting that their fitness may depend on inherited variants, extrinsic factors or distributions of fitness effects.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
9.8
作者：
Forsberg, Lars A.;Rasi, Chiara;Dumanski, Jan P.
通讯作者：
Dumanski, Jan P.
影响因子：
20.3
作者：
van Zeventer, Isabelle A.;de Graaf, Aniek O.;Huls, Gerwin
通讯作者：
Huls, Gerwin
影响因子：
11.4
作者：
Tasaka, T.;Tohyama, K.;Ozawa, K.
通讯作者：
Ozawa, K.