自闭症的遗传因素
“自闭症候群”(ASDs)是一类症候，其典型特征是重复性行为、严重受限的兴趣以及社交和沟通有困难。ASD具有高度遗传性，然而造成这种病症的遗传决定因素在很大程度上仍然不清楚。
一项全基因组分析显示，ASD患者所携带的“罕见版本号变异体”(CNVs，即版本号在不同基因组之间有所不同的DNA片段)较多，这种情况要么是遗传的，要么是后天形成的。这些分析结果表明，几个新基因可能是ASD的候选基因，同时也指出了细胞增殖、投射（projection）和运动以及特定信号作用通道在这种病症中的重要性。
Nature doi:10.1038/nature09146
Functional impact of global rare copy number variation in autism spectrum disorders
Dalila Pinto,Alistair T. Pagnamenta,Lambertus Klei,Richard Anney,Daniele Merico,Regina Regan,Judith Conroy,Tiago R. Magalhaes,Catarina Correia,Brett S. Abrahams,Joana Almeida,Elena Bacchelli,Gary D. Bader,Anthony J. Bailey,Gillian Baird,Agatino Battaglia,Tom Berney,Nadia Bolshakova,Sven B?lte,Patrick F. Bolton,Thomas Bourgeron,Sean Brennan,Jessica Brian,Susan E. Bryson,Andrew R. Carson,Guillermo Casallo,Jillian Casey,Brian H.Y. Chung,Lynne Cochrane,Christina Corsello,Emily L. Crawford,Andrew Crossett,Cheryl Cytrynbaum,Geraldine Dawson,Maretha de Jonge,Richard Delorme,Irene Drmic,Eftichia Duketis,Frederico Duque,Annette Estes,Penny Farrar,Bridget A. Fernandez,Susan E. Folstein,Eric Fombonne,Christine M. Freitag,John Gilbert,Christopher Gillberg,Joseph T. Glessner,Jeremy Goldberg,Andrew Green,Jonathan Green,Stephen J. Guter,Hakon Hakonarson,Elizabeth A. Heron,Matthew Hill,Richard Holt,Jennifer L. Howe,Gillian Hughes,Vanessa Hus,Roberta Igliozzi,Cecilia Kim,Sabine M. Klauck,Alexander Kolevzon,Olena Korvatska,Vlad Kustanovich,Clara M. Lajonchere,Janine A. Lamb,Magdalena Laskawiec,Marion Leboyer,Ann Le Couteur,Bennett L. Leventhal,Anath C. Lionel,Xiao-Qing Liu,Catherine Lord,Linda Lotspeich,Sabata C. Lund,Elena Maestrini,William Mahoney,Carine Mantoulan,Christian R. Marshall,Helen McConachie,Christopher J. McDougle,Jane McGrath,William M. McMahon,Alison Merikangas,Ohsuke Migita,Nancy J. Minshew,Ghazala K. Mirza,Jeff Munson,Stanley F. Nelson,Carolyn Noakes,Abdul Noor,Gudrun Nygren,Guiomar Oliveira,Katerina Papanikolaou,Jeremy R. Parr,Barbara Parrini,Tara Paton,Andrew Pickles,Marion Pilorge,Joseph Piven,Chris P. Ponting,David J. Posey,Annemarie Poustka,Fritz Poustka,Aparna Prasad,Jiannis Ragoussis,Katy Renshaw,Jessica Rickaby,Wendy Roberts,Kathryn Roeder,Bernadette Roge,Michael L. Rutter,Laura J. Bierut,John P. Rice,Jeff Salt,Katherine Sansom,Daisuke Sato,Ricardo Segurado,Ana F. Sequeira,Lili Senman,Naisha Shah,Val C. Sheffield,Latha Soorya,Inês Sousa,Olaf Stein,Nuala Sykes,Vera Stoppioni,Christina Strawbridge,Raffaella Tancredi,Katherine Tansey,Bhooma Thiruvahindrapduram,Ann P. Thompson,Susanne Thomson,Ana Tryfon,John Tsiantis,Herman Van Engeland,John B. Vincent,Fred Volkmar,Simon Wallace,Kai Wang,Zhouzhi Wang,Thomas H. Wassink,Caleb Webber,Rosanna Weksberg,Kirsty Wing,Kerstin Wittemeyer,Shawn Wood,Jing Wu,Brian L. Yaspan,Danielle Zurawiecki,Lonnie Zwaigenbaum,Joseph D. Buxbaum,Rita M. Cantor,Edwin H. Cook,Hilary Coon,Michael L. Cuccaro,Bernie Devlin,Sean Ennis,Louise Gallagher,Daniel H. Geschwind,Michael Gill,Jonathan L. Haines,Joachim Hallmayer,Judith Miller,Anthony P. Monaco,John I. Nurnberger Jr,Andrew D. Paterson,Margaret A. Pericak-Vance,Gerard D. Schellenberg,Peter Szatmari,Astrid M. Vicente,Veronica J. Vieland,Ellen M. Wijsman,Stephen W. Scherer,James S. Sutcliffe& Catalina Betancur
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable (~90%)3, the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. #p#分页标题#e#When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4?×?10-4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53–PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
