Anne B Arnett1,2, Tianyun Wang3, Evan E Eichler3,4, Raphael A Bernier5. 1. Department of Psychiatry and Behavioral Sciences, University of Washington, CHDD, Box 357920, Seattle, WA, 98195, USA. arnettab@uw.edu. 2. Department of Psychiatry and Behavioral Medicine, Seattle Children's Hospital, Seattle, WA, USA. arnettab@uw.edu. 3. Department of Genome Sciences, University of Washington, Seattle, WA, USA. 4. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA. 5. Department of Psychiatry and Behavioral Sciences, University of Washington, CHDD, Box 357920, Seattle, WA, 98195, USA.
Abstract
BACKGROUND: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are common diagnoses with highly heterogeneous phenotypes and etiology. The genetics-first approach to research on NDDs has led to the identification of hundreds of genes conferring risk for ASD, ID, and related symptoms. MAIN BODY: Although relatively few individuals with NDDs share likely gene-disruptive (LGD) mutations in the same gene, characterization of overlapping functions, protein networks, and temporospatial expression patterns among these genes has led to increased understanding of the neurobiological etiology of NDDs. This shift in focus away from single genes and toward broader gene-brain-behavior pathways has been accelerated by the development of publicly available transcriptomic databases, cell type-specific research methods, and sequencing of non-coding genomic regions. CONCLUSIONS: The genetics-first approach to research on NDDs has advanced the identification of critical protein function pathways and temporospatial expression patterns, expanding the impact of this research beyond individuals with single-gene mutations to the broader population of patients with NDDs.
BACKGROUND:Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are common diagnoses with highly heterogeneous phenotypes and etiology. The genetics-first approach to research on NDDs has led to the identification of hundreds of genes conferring risk for ASD, ID, and related symptoms. MAIN BODY: Although relatively few individuals with NDDs share likely gene-disruptive (LGD) mutations in the same gene, characterization of overlapping functions, protein networks, and temporospatial expression patterns among these genes has led to increased understanding of the neurobiological etiology of NDDs. This shift in focus away from single genes and toward broader gene-brain-behavior pathways has been accelerated by the development of publicly available transcriptomic databases, cell type-specific research methods, and sequencing of non-coding genomic regions. CONCLUSIONS: The genetics-first approach to research on NDDs has advanced the identification of critical protein function pathways and temporospatial expression patterns, expanding the impact of this research beyond individuals with single-gene mutations to the broader population of patients with NDDs.
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Authors: Holly A F Stessman; Bo Xiong; Bradley P Coe; Tianyun Wang; Kendra Hoekzema; Michaela Fenckova; Malin Kvarnung; Jennifer Gerdts; Sandy Trinh; Nele Cosemans; Laura Vives; Janice Lin; Tychele N Turner; Gijs Santen; Claudia Ruivenkamp; Marjolein Kriek; Arie van Haeringen; Emmelien Aten; Kathryn Friend; Jan Liebelt; Christopher Barnett; Eric Haan; Marie Shaw; Jozef Gecz; Britt-Marie Anderlid; Ann Nordgren; Anna Lindstrand; Charles Schwartz; R Frank Kooy; Geert Vandeweyer; Celine Helsmoortel; Corrado Romano; Antonino Alberti; Mirella Vinci; Emanuela Avola; Stefania Giusto; Eric Courchesne; Tiziano Pramparo; Karen Pierce; Srinivasa Nalabolu; David G Amaral; Ingrid E Scheffer; Martin B Delatycki; Paul J Lockhart; Fereydoun Hormozdiari; Benjamin Harich; Anna Castells-Nobau; Kun Xia; Hilde Peeters; Magnus Nordenskjöld; Annette Schenck; Raphael A Bernier; Evan E Eichler Journal: Nat Genet Date: 2017-02-13 Impact factor: 38.330