Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
作者： Zachary Warren , Amy Swanson , Amy Nicholson , James S. Sutcliffe , A. Pablo Juarez
DOI: 10.1038/S41525-019-0093-8
关键词:
摘要: Autism spectrum disorder (ASD) is a genetically heterogeneous condition, caused by combination of rare de novo and inherited variants as well common in at least several hundred genes. However, significantly larger sample sizes are needed to identify the complete set genetic risk factors. We conducted pilot study for SPARK (SPARKForAutism.org) 457 families with ASD, all consented online. Whole exome sequencing (WES) genotyping data were generated each family using DNA from saliva. identified genes loci that clinically recognized causes or significant contributors ASD 10.4% without previous findings. Additionally, we possibly associated autism an additional 3.4% families. A meta-analysis TADA framework false discovery rate (FDR) 0.2 provides statistical support 34 one damaging variant SPARK. Nine these (BRSK2, DPP6, EGR3, FEZF2, ITSN1, KDM1B, NR4A2, PAX5 RALGAPB) newly emerging autism, which BRSK2 has strongest gene (TADA q-value = 0.0015). Future studies leveraging thousands individuals have enrolled likely further clarify factors allow accelerate research incorporates etiology.
sci-hub.st 参考文章(104)
Warren G. Tourtellotte, Jeffrey Milbrandt, Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3 Nature Genetics. ,vol. 20, pp. 87- 91 ,(1998) , 10.1038/1757
Niklas Krumm, Tychele N Turner, Carl Baker, Laura Vives, Kiana Mohajeri, Kali Witherspoon, Archana Raja, Bradley P Coe, Holly A Stessman, Zong-Xiao He, Suzanne M Leal, Raphael Bernier, Evan E Eichler, Excess of rare, inherited truncating mutations in autism. Nature Genetics. ,vol. 47, pp. 582- 588 ,(2015) , 10.1038/NG.3303
James W. Bodfish, Frank J. Symons, Dawn E. Parker, Mark H. Lewis, Varieties of repetitive behavior in autism: comparisons to mental retardation. Journal of Autism and Developmental Disorders. ,vol. 30, pp. 237- 243 ,(2000) , 10.1023/A:1005596502855
Gabor Marth, Erik Garrison, Haplotype-based variant detection from short-read sequencing arXiv: Genomics. ,(2012)
Jonathan S. Packer, Evan K. Maxwell, Colm O’Dushlaine, Alexander E. Lopez, Frederick E. Dewey, Rostislav Chernomorsky, Aris Baras, John D. Overton, Lukas Habegger, Jeffrey G. Reid, CLAMMS: a scalable algorithm for calling common and rare copy number variants from exome sequencing data. Bioinformatics. ,vol. 32, pp. 133- 135 ,(2015) , 10.1093/BIOINFORMATICS/BTV547
Andrew S Allen, Samuel F Berkovic, Patrick Cossette, Norman Delanty, Dennis Dlugos, Evan E Eichler, Michael P Epstein, Tracy Glauser, David B Goldstein, Yujun Han, Erin L Heinzen, Yuki Hitomi, Katherine B Howell, Michael R Johnson, Ruben Kuzniecky, Daniel H Lowenstein, Yi-Fan Lu, Maura RZ Madou, Anthony G Marson, Heather C Mefford, Sahar Esmaeeli Nieh, Terence J O'Brien, Ruth Ottman, Slavé Petrovski, Annapurna Poduri, Elizabeth K Ruzzo, Ingrid E Scheffer, Elliott H Sherr, Christopher J Yuskaitis, Epilepsy Phenome, Genome Project, Bassel Abou-Khalil, Brian K Alldredge, Jocelyn F Bautista, Alex Boro, Gregory D Cascino, Damian Consalvo, Patricia Crumrine, Orrin Devinsky, Miguel Fiol, Nathan B Fountain, Jacqueline French, Daniel Friedman, Eric B Geller, Simon Glynn, Sheryl R Haut, Jean Hayward, Sandra L Helmers, Sucheta Joshi, Andres Kanner, Heidi E Kirsch, Robert C Knowlton, Eric H Kossoff, Rachel Kuperman, Shannon M McGuire, Paul V Motika, Edward J Novotny, Juliann M Paolicchi, Jack M Parent, Kristen Park, Renée A Shellhaas, Jerry J Shih, Rani Singh, Joseph Sirven, Michael C Smith, Joseph Sullivan, Liu Lin Thio, Anu Venkat, Eileen PG Vining, Gretchen K Von Allmen, Judith L Weisenberg, Peter Widdess-Walsh, Melodie R Winawer, Epi4K Consortium, De novo mutations in epileptic encephalopathies Nature. ,vol. 501, pp. 217- 221 ,(2013) , 10.1038/NATURE12439
Menachem Fromer, Shaun M. Purcell, Using XHMM software to detect copy number variation in whole-exome sequencing data Current protocols in human genetics. ,vol. 81, ,(2014) , 10.1002/0471142905.HG0723S81
Ivan Iossifov, Dan Levy, Jeremy Allen, Kenny Ye, Michael Ronemus, Yoon-ha Lee, Boris Yamrom, Michael Wigler, Low load for disruptive mutations in autism genes and their biased transmission Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 201516376- ,(2015) , 10.1073/PNAS.1516376112
Àlex Bayés, Louie N van de Lagemaat, Mark O Collins, Mike D R Croning, Ian R Whittle, Jyoti S Choudhary, Seth G N Grant, Characterization of the proteome, diseases and evolution of the human postsynaptic density Nature Neuroscience. ,vol. 14, pp. 19- 21 ,(2011) , 10.1038/NN.2719
Guan Ning Lin, Roser Corominas, Irma Lemmens, Xinping Yang, Jan Tavernier, David E. Hill, Marc Vidal, Jonathan Sebat, Lilia M. Iakoucheva, Spatiotemporal 16p11.2 Protein Network Implicates Cortical Late Mid-Fetal Brain Development and KCTD13-Cul3-RhoA Pathway in Psychiatric Diseases Neuron. ,vol. 85, pp. 742- 754 ,(2015) , 10.1016/J.NEURON.2015.01.010