@article{08441215e3ac43de82e14fcff377dccb,
title = "The Role of De Novo Noncoding Regulatory Mutations in Neurodevelopmental Disorders",
abstract = "Advances in sequencing technology have significantly expanded our understanding of the genetics of autism and neurodevelopmental disorders (NDDs). Continued technological improvements and cost reductions have now shifted the focus to investigations into the functional noncoding portions of the genome. There is a patient trend toward an excess of de novo and potentially disruptive mutations among conserved noncoding sequences implicated in the regulation of genes. The signals become stronger when restricted to genes already implicated in NDDs, but de novo mutation in such elements is estimated to account for <5% of patients. Larger sample sizes, improved variant detection, functional testing, and better approaches to classify noncoding variation will be required to identify specific pathogenic variants underlying disease.",
keywords = "autism, genetic architecture, genome sequencing, neurodevelopmental disorders, noncoding, regulatory mutations",
author = "Turner, {Tychele N.} and Eichler, {Evan E.}",
note = "Funding Information: We thank Jay Shendure, Daniela Witten, Jessica Chong, and members of the Eichler laboratory for helpful discussions regarding the contents of this review. We thank Bernie Devlin, Michael Talkowski, and Stephan Sanders for letting us reproduce a figure from their Nature Genetics paper in this review. We thank Bradley Coe and Mark Chaisson for early access to data included in this review. We also thank Tonia Brown for edits. The authors{\textquoteright} research is supported, in part, by grants from the US National Institutes of Health (NIH R01MH101221 ) to E.E.E. and the National Institute of Mental Health to T.N.T. ( 1K99MH117165 ). We are grateful to all of the families who participated in research studies to understand the genetic risk factors underlying autism and NDDs. E.E.E. is an investigator of the Howard Hughes Medical Institute. Funding Information: We thank Jay Shendure, Daniela Witten, Jessica Chong, and members of the Eichler laboratory for helpful discussions regarding the contents of this review. We thank Bernie Devlin, Michael Talkowski, and Stephan Sanders for letting us reproduce a figure from their Nature Genetics paper in this review. We thank Bradley Coe and Mark Chaisson for early access to data included in this review. We also thank Tonia Brown for edits. The authors? research is supported, in part, by grants from the US National Institutes of Health (NIH R01MH101221) to E.E.E. and the National Institute of Mental Health to T.N.T. (1K99MH117165). We are grateful to all of the families who participated in research studies to understand the genetic risk factors underlying autism and NDDs. E.E.E. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2019",
month = feb,
doi = "10.1016/j.tins.2018.11.002",
language = "English",
volume = "42",
pages = "115--127",
journal = "Trends in Neurosciences",
issn = "0166-2236",
number = "2",
}