Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations.
Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations.
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DOI：
10.1038/s41586-018-0321-x
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发表时间：
2018-07
期刊：
影响因子：
64.8
通讯作者：
Price AL
中科院分区：
文献类型：
--
作者：
Loh PR;Genovese G;Handsaker RE;Finucane HK;Reshef YA;Palamara PF;Birmann BM;Talkowski ME;Bakhoum SF;McCarroll SA;Price AL
The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations (mCAs) of length 50kb–249Mb that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using new phase-based computational techniques (estimated false discovery rate, 6–9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3/TARSL2, and FRA10B), we identified a likely causal variant that acted with high penetrance (5–50%). Inherited alleles at one locus appeared to affect the probability of somatic mutation, and at three other loci to be objects of positive or negative clonal selection. Several specific mCAs strongly associated with future hematological malignancies. Our results reveal a multitude of paths toward clonal expansions with a wide range of effects on human health.
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影响因子：
12.3
作者：
Castel SE;Levy-Moonshine A;Mohammadi P;Banks E;Lappalainen T
通讯作者：
Lappalainen T
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：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian