Rates of contributory de novo mutation in high and low-risk autism families.
Rates of contributory de novo mutation in high and low-risk autism families.
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DOI：
10.1038/s42003-021-02533-z
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发表时间：
2021-09-01
影响因子：
5.9
通讯作者：
Iossifov I
中科院分区：
文献类型：
--
作者：
Yoon S;Munoz A;Yamrom B;Lee YH;Andrews P;Marks S;Wang Z;Reeves C;Winterkorn L;Krieger AM;Buja A;Pradhan K;Ronemus M;Baldwin KK;Levy D;Wigler M;Iossifov I
自闭症发生在高风险和低风险的家庭中。新生突变导致低风险家庭中自闭症的发病率较高，因为受影响的单纯家庭的发病率高于未受影响的兄弟姐妹。但低风险家庭的贡献程度不能仅根据单一家庭来确定，因为它们是低风险和高风险的混合体。此前尚未严格确定高风险家庭（即多重家庭）的近纯群体中的从头突变率。此外，基于低分辨率微阵列和全外显子组测序的研究低估了从头突变的发生率。在这里，我们报告了来自西蒙斯单纯收集（SSC）的两个单一家族和来自自闭症遗传资源交换（AGRE）的多重家族的全基因组序列（WGS）的发现。在去除细胞系遗传漂变过多的多重样本后，我们发现多重样本中从头突变的贡献明显小于单一样本中的贡献。我们使用全基因组测序（WGS）来提供高分辨率的 CNV 图谱，并分析多个编码区域，并向上修正由于针对内含子的从头事件过多而导致的单纯自闭症的发生率。根据这项研究，我们现在估计低风险家庭中 52-67% 的自闭症病例以及所有自闭症病例中的 30-39% 是由新生事件造成的。尹、穆尼奥斯等人。使用来自自闭症家庭集合的全基因组序列数据来调查自闭症高风险和低风险家庭中从头编码和非编码变异的比率。他们证明，de novo内含子变异会增加自闭症的风险，de novo变异的贡献在低风险家庭中显着更大，de novo变异占所有自闭症病例的30-39%。
Autism arises in high and low-risk families. De novo mutation contributes to autism incidence in low-risk families as there is a higher incidence in the affected of the simplex families than in their unaffected siblings. But the extent of contribution in low-risk families cannot be determined solely from simplex families as they are a mixture of low and high-risk. The rate of de novo mutation in nearly pure populations of high-risk families, the multiplex families, has not previously been rigorously determined. Moreover, rates of de novo mutation have been underestimated from studies based on low resolution microarrays and whole exome sequencing. Here we report on findings from whole genome sequence (WGS) of both simplex families from the Simons Simplex Collection (SSC) and multiplex families from the Autism Genetic Resource Exchange (AGRE). After removing the multiplex samples with excessive cell-line genetic drift, we find that the contribution of de novo mutation in multiplex is significantly smaller than the contribution in simplex. We use WGS to provide high resolution CNV profiles and to analyze more than coding regions, and revise upward the rate in simplex autism due to an excess of de novo events targeting introns. Based on this study, we now estimate that de novo events contribute to 52–67% of cases of autism arising from low risk families, and 30–39% of cases of all autism. Yoon, Munoz, et al. investigate the rate of de novo coding and non-coding variants in families with high- and low-risk for autism using whole-genome sequence data from collections of families with autism. They demonstrate that de novo intronic variants increase the risk of autism, that the contribution of de novo variants is significantly larger in low-risk families, and that de novo variants contribute to 30-39% of cases of all autism.
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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
自闭症谱系障碍中基因和细胞途径的收敛性。
影响因子：
9.8
作者：
Pinto D;Delaby E;Merico D;Barbosa M;Merikangas A;Klei L;Thiruvahindrapuram B;Xu X;Ziman R;Wang Z;Vorstman JA;Thompson A;Regan R;Pilorge M;Pellecchia G;Pagnamenta AT;Oliveira B;Marshall CR;Magalhaes TR;Lowe JK;Howe JL;Griswold AJ;Gilbert J;Duketis E;Dombroski BA;De Jonge MV;Cuccaro M;Crawford EL;Correia CT;Conroy J;Conceição IC;Chiocchetti AG;Casey JP;Cai G;Cabrol C;Bolshakova N;Bacchelli E;Anney R;Gallinger S;Cotterchio M;Casey G;Zwaigenbaum L;Wittemeyer K;Wing K;Wallace S;van Engeland H;Tryfon A;Thomson S;Soorya L;Rogé B;Roberts W;Poustka F;Mouga S;Minshew N;McInnes LA;McGrew SG;Lord C;Leboyer M;Le Couteur AS;Kolevzon A;Jiménez González P;Jacob S;Holt R;Guter S;Green J;Green A;Gillberg C;Fernandez BA;Duque F;Delorme R;Dawson G;Chaste P;Café C;Brennan S;Bourgeron T;Bolton PF;Bölte S;Bernier R;Baird G;Bailey AJ;Anagnostou E;Almeida J;Wijsman EM;Vieland VJ;Vicente AM;Schellenberg GD;Pericak-Vance M;Paterson AD;Parr JR;Oliveira G;Nurnberger JI;Monaco AP;Maestrini E;Klauck SM;Hakonarson H;Haines JL;Geschwind DH;Freitag CM;Folstein SE;Ennis S;Coon H;Battaglia A;Szatmari P;Sutcliffe JS;Hallmayer J;Gill M;Cook EH;Buxbaum JD;Devlin B;Gallagher L;Betancur C;Scherer SW
通讯作者：
Scherer SW
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
影响因子：
30.8
作者：
Lee, S. Hong;Ripke, Stephan;Neale, Benjamin M.;Faraone, Stephen V.;Purcell, Shaun M.;Perlis, Roy H.;Mowry, Bryan J.;Thapar, Anita;Goddard, Michael E.;Witte, John S.;Absher, Devin;Agartz, Ingrid;Akil, Huda;Amin, Farooq;Andreassen, Ole A.;Anjorin, Adebayo;Anney, Richard;Anttila, Verneri;Arking, Dan E.;Asherson, Philip;Azevedo, Maria H.;Backlund, Lena;Badner, Judith A.;Bailey, Anthony J.;Banaschewski, Tobias;Barchas, Jack D.;Barnes, Michael R.;Barrett, Thomas B.;Bass, Nicholas;Battaglia, Agatino;Bauer, Michael;Bayes, Monica;Bellivier, Frank;Bergen, Sarah E.;Berrettini, Wade;Betancur, Catalina;Bettecken, Thomas;Biederman, Joseph;Binder, Elisabeth B.;Black, Donald W.;Blackwood, Douglas H. R.;Bloss, Cinnamon S.;Boehnke, Michael;Boomsma, Dorret I.;Breen, Gerome;Breuer, Rene;Bruggeman, Richard;Cormican, Paul;Buccola, Nancy G.;Buitelaar, Jan K.;Bunney, William E.;Buxbaum, Joseph D.;Byerley, William F.;Byrne, Enda M.;Caesar, Sian;Cahn, Wiepke;Cantor, Rita M.;Casas, Miguel;Chakravarti, Aravinda;Chambert, Kimberly;Choudhury, Khalid;Cichon, Sven;Cloninger, C. Robert;Collier, David A.;Cook, Edwin H.;Coon, Hilary;Cormand, Bru;Corvin, Aiden;Coryell, William H.;Craig, David W.;Craig, Ian W.;Crosbie, Jennifer;Cuccaro, Michael L.;Curtis, David;Czamara, Darina;Datta, Susmita;Dawson, Geraldine;Day, Richard;De Geus, Eco J.;Degenhardt, Franziska;Djurovic, Srdjan;Donohoe, Gary J.;Doyle, Alysa E.;Duan, Jubao;Dudbridge, Frank;Duketis, Eftichia;Ebstein, Richard P.;Edenberg, Howard J.;Elia, Josephine;Ennis, Sean;Etain, Bruno;Fanous, Ayman;Farmer, Anne E.;Ferrier, I. Nicol;Flickinger, Matthew;Fombonne, Eric;Foroud, Tatiana;Frank, Josef;Franke, Barbara;Fraser, Christine;Freedman, Robert;Freimer, Nelson B.;Freitag, Christine M.;Friedl, Marion;Frisen, Louise;Gallagher, Louise;Gejman, Pablo V.;Georgieva, Lyudmila;Gershon, Elliot S.;Geschwind, Daniel H.;Giegling, Ina;Gill, Michael;Gordon, Scott D.;Gordon-Smith, Katherine;Green, Elaine K.;Greenwood, Tiffany A.;Grice, Dorothy E.;Gross, Magdalena;Grozeva, Detelina;Guan, Weihua;Gurling, Hugh;De Haan, Lieuwe;Haines, Jonathan L.;Hakonarson, Hakon;Hallmayer, Joachim;Hamilton, Steven P.;Hamshere, Marian L.;Hansen, Thomas F.;Hartmann, Annette M.;Hautzinger, Martin;Heath, Andrew C.;Henders, Anjali K.;Herms, Stefan;Hickie, Ian B.;Hipolito, Maria;Hoefels, Susanne;Holmans, Peter A.;Holsboer, Florian;Hoogendijk, Witte J.;Hottenga, Jouke-Jan;Hultman, Christina M.;Hus, Vanessa;Ingason, Andres;Ising, Marcus;Jamain, Stephane;Jones, Edward G.;Jones, Ian;Jones, Lisa;Tzeng, Jung-Ying;Kaehler, Anna K.;Kahn, Rene S.;Kandaswamy, Radhika;Keller, Matthew C.;Kennedy, James L.;Kenny, Elaine;Kent, Lindsey;Kim, Yunjung;Kirov, George K.;Klauck, Sabine M.;Klei, Lambertus;Knowles, James A.;Kohli, Martin A.;Koller, Daniel L.;Konte, Bettina;Korszun, Ania;Krabbendam, Lydia;Krasucki, Robert;Kuntsi, Jonna;Kwan, Phoenix;Landen, Mikael;Langstrom, Niklas;Lathrop, Mark;Lawrence, Jacob;Lawson, William B.;Leboyer, Marion;Ledbetter, David H.;Lee, Phil H.;Lencz, Todd;Lesch, Klaus-Peter;Levinson, Douglas F.;Lewis, Cathryn M.;Li, Jun;Lichtenstein, Paul;Lieberman, Jeffrey A.;Lin, Dan-Yu;Linszen, Don H.;Liu, Chunyu;Lohoff, Falk W.;Loo, Sandra K.;Lord, Catherine;Lowe, Jennifer K.;Lucae, Susanne;MacIntyre, Donald J.;Madden, Pamela A. F.;Maestrini, Elena;Magnusson, Patrik K. E.;Mahon, Pamela B.;Maier, Wolfgang;Malhotra, Anil K.;Mane, Shrikant M.;Martin, Christa L.;Martin, Nicholas G.;Mattheisen, Manuel;Matthews, Keith;Mattingsdal, Morten;McCarroll, Steven A.;McGhee, Kevin A.;McGough, James J.;McGrath, Patrick J.;McGuffin, Peter;McInnis, Melvin G.;McIntosh, Andrew;McKinney, Rebecca;McLean, Alan W.;McMahon, Francis J.;McMahon, William M.;McQuillin, Andrew;Medeiros, Helena;Medland, Sarah E.;Meier, Sandra;Melle, Ingrid;Meng, Fan;Meyer, Jobst;Middeldorp, Christel M.;Middleton, Lefkos;Milanova, Vihra;Miranda, Ana;Monaco, Anthony P.;Montgomery, Grant W.;Moran, Jennifer L.;Moreno-De-Luca, Daniel;Morken, Gunnar;Morris, Derek W.;Morrow, Eric M.;Moskvina, Valentina;Muglia, Pierandrea;Muehleisen, Thomas W.;Muir, Walter J.;Mueller-Myhsok, Bertram;Murtha, Michael;Myers, Richard M.;Myin-Germeys, Inez;Neale, Michael C.;Nelson, Stan F.;Nievergelt, Caroline M.;Nikolov, Ivan;Nimgaonkar, Vishwajit;Nolen, Willem A.;Noethen, Markus M.;Nurnberger, John I.;Nwulia, Evaristus A.;Nyholt, Dale R.;O'Dushlaine, Colm;Oades, Robert D.;Olincy, Ann;Oliveira, Guiomar;Olsen, Line;Ophoff, Roel A.;Osby, Urban;Owen, Michael J.;Palotie, Aarno;Parr, Jeremy R.;Paterson, Andrew D.;Pato, Carlos N.;Pato, Michele T.;Penninx, Brenda W.;Pergadia, Michele L.;Pericak-Vance, Margaret A.;Pickard, Benjamin S.;Pimm, Jonathan;Piven, Joseph;Posthuma, Danielle;Potash, James B.;Poustka, Fritz;Propping, Peter;Puri, Vinay;Quested, Digby J.;Quinn, Emma M.;Antoni Ramos-Quiroga, Josep;Rasmussen, Henrik B.;Raychaudhuri, Soumya;Rehnstroem, Karola;Reif, Andreas;Ribases, Marta;Rice, John P.;Rietschel, Marcella;Roeder, Kathryn;Roeyers, Herbert;Rossin, Lizzy;Rothenberger, Aribert;Rouleau, Guy;Ruderfer, Douglas;Rujescu, Dan;Sanders, Alan R.;Sanders, Stephan J.;Santangelo, Susan L.;Sergeant, Joseph A.;Schachar, Russell;Schalling, Martin;Schatzberg, Alan F.;Scheftner, William A.;Schellenberg, Gerard D.;Scherer, Stephen W.;Schork, Nicholas J.;Schulze, Thomas G.;Schumacher, Johannes;Schwarz, Markus;Scolnick, Edward;Scott, Laura J.;Shi, Jianxin;Shilling, Paul D.;Shyn, Stanley I.;Silverman, Jeremy M.;Slager, Susan L.;Smalley, Susan L.;Smit, Johannes H.;Smith, Erin N.;Sonuga-Barke, Edmund J. S.;St Clair, David;State, Matthew;Steffens, Michael;Steinhausen, Hans-Christoph;Strauss, John S.;Strohmaier, Jana;Stroup, T. Scott;Sutcliffe, James S.;Szatmari, Peter;Szelinger, Szabocls;Thirumalai, Srinivasa;Thompson, Robert C.;Todorov, Alexandre A.;Tozzi, Federica;Treutlein, Jens;Uhr, Manfred;van den Oord, Edwin J. C. G.;Van Grootheest, Gerard;Van Os, Jim;Vicente, Astrid M.;Vieland, Veronica J.;Vincent, John B.;Visscher, Peter M.;Walsh, Christopher A.;Wassink, Thomas H.;Watson, Stanley J.;Weissman, Myrna M.;Werge, Thomas;Wienker, Thomas F.;Wijsman, Ellen M.;Willemsen, Gonneke;Williams, Nigel;Willsey, A. Jeremy;Witt, Stephanie H.;Xu, Wei;Young, Allan H.;Yu, Timothy W.;Zammit, Stanley;Zandi, Peter P.;Zhang, Peng;Zitman, Frans G.;Zoellner, Sebastian;Devlin, Bernie;Kelsoe, John R.;Sklar, Pamela;Daly, Mark J.;O'Donovan, Michael C.;Craddock, Nicholas;Sullivan, Patrick F.;Smoller, Jordan W.;Kendler, Kenneth S.;Wray, Naomi R.
通讯作者：
Wray, Naomi R.
影响因子：
56.9
作者：
An, Joon-Yong;Lin, Kevin;Sanders, Stephan J.
通讯作者：
Sanders, Stephan J.