%0 Journal Article %1 Iossifov2012285 %A Iossifov, Ivan %A Ronemus, Michael %A Levy, Dan %A Wang, Zihua %A Hakker, Inessa %A Rosenbaum, Julie %A Yamrom, Boris %A ha Lee, Yoon %A Narzisi, Giuseppe %A Leotta, Anthony %A Kendall, Jude %A Grabowska, Ewa %A Ma, Beicong %A Marks, Steven %A Rodgers, Linda %A Stepansky, Asya %A Troge, Jennifer %A Andrews, Peter %A Bekritsky, Mitchell %A Pradhan, Kith %A Ghiban, Elena %A Kramer, Melissa %A Parla, Jennifer %A Demeter, Ryan %A Fulton, Lucinda L. %A Fulton, Robert S. %A Magrini, Vincent J. %A Ye, Kenny %A Darnell, Jennifer C. %A Darnell, Robert B. %A Mardis, Elaine R. %A Wilson, Richard K. %A Schatz, Michael C. %A McCombie, W. Richard %A Wigler, Michael %D 2012 %J Neuron %K autism de.novo %N 2 %P 285 - 299 %R 10.1016/j.neuron.2012.04.009 %T De Novo Gene Disruptions in Children on the Autistic Spectrum %U http://www.sciencedirect.com/science/article/pii/S0896627312003406 %V 74 %X Summary Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.

@article{Iossifov2012285, abstract = {Summary Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.}, added-at = {2013-02-24T03:24:12.000+0100}, author = {Iossifov, Ivan and Ronemus, Michael and Levy, Dan and Wang, Zihua and Hakker, Inessa and Rosenbaum, Julie and Yamrom, Boris and ha Lee, Yoon and Narzisi, Giuseppe and Leotta, Anthony and Kendall, Jude and Grabowska, Ewa and Ma, Beicong and Marks, Steven and Rodgers, Linda and Stepansky, Asya and Troge, Jennifer and Andrews, Peter and Bekritsky, Mitchell and Pradhan, Kith and Ghiban, Elena and Kramer, Melissa and Parla, Jennifer and Demeter, Ryan and Fulton, Lucinda L. and Fulton, Robert S. and Magrini, Vincent J. and Ye, Kenny and Darnell, Jennifer C. and Darnell, Robert B. and Mardis, Elaine R. and Wilson, Richard K. and Schatz, Michael C. and McCombie, W. Richard and Wigler, Michael}, biburl = {https://www.bibsonomy.org/bibtex/24ab05b569b429ccf26c0bc7f2bfcb08f/ytyoun}, doi = {10.1016/j.neuron.2012.04.009}, interhash = {2e3af4dca9f41569ebae008dd8b35fd5}, intrahash = {4ab05b569b429ccf26c0bc7f2bfcb08f}, issn = {0896-6273}, journal = {Neuron}, keywords = {autism de.novo}, number = 2, pages = {285 - 299}, timestamp = {2013-02-24T03:24:12.000+0100}, title = {De Novo Gene Disruptions in Children on the Autistic Spectrum}, url = {http://www.sciencedirect.com/science/article/pii/S0896627312003406}, volume = 74, year = 2012 }