De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families.
De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families.
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通过2396个家庭的基因组测序揭示了从头结构突变率和原始偏见。
DOI：
10.1016/j.ajhg.2021.02.012
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发表时间：
2021-04-01
影响因子：
9.8
通讯作者：
Quinlan AR
中科院分区：
文献类型：
--
作者：
Belyeu JR;Brand H;Wang H;Zhao X;Pedersen BS;Feusier J;Gupta M;Nicholas TJ;Brown J;Baird L;Devlin B;Sanders SJ;Jorde LB;Talkowski ME;Quinlan AR
Each human genome includes de novo mutations that arose during gametogenesis. While these germline mutations represent a fundamental source of new genetic diversity, they can also create deleterious alleles that impact fitness. Whereas the rate and patterns of point mutations in the human germline are now well understood, far less is known about the frequency and features that impact de novo structural variants (dnSVs). We report a family-based study of germline mutations among 9,599 human genomes from 33 multigenerational CEPH-Utah families and 2,384 families from the Simons Foundation Autism Research Initiative. We find that de novo structural mutations detected by alignment-based, short-read WGS occur at an overall rate of at least 0.160 events per genome in unaffected individuals, and we observe a significantly higher rate (0.206 per genome) in ASD-affected individuals. In both probands and unaffected samples, nearly 73% of de novo structural mutations arose in paternal gametes, and we predict most de novo structural mutations to be caused by mutational mechanisms that do not require sequence homology. After multiple testing correction, we did not observe a statistically significant correlation between parental age and the rate of de novo structural variation in offspring. These results highlight that a spectrum of mutational mechanisms contribute to germline structural mutations and that these mechanisms most likely have markedly different rates and selective pressures than those leading to point mutations.
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影响因子：
7
作者：
Gardner EJ;Lam VK;Harris DN;Chuang NT;Scott EC;Pittard WS;Mills RE;1000 Genomes Project Consortium;Devine SE
通讯作者：
Devine SE
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
56.9
作者：
An, Joon-Yong;Lin, Kevin;Sanders, Stephan J.
通讯作者：
Sanders, Stephan J.
影响因子：
9.8
作者：
Brand, Harrison;Collins, Ryan L.;Talkowski, Michael E.
通讯作者：
Talkowski, Michael E.
影响因子：
14.5
作者：
Arana ME;Kunkel TA
通讯作者：
Kunkel TA