Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Network analysis of genome-wide selective constraint reveals a gene network active in early fetal brain intolerant of mutation

Jinmyung Choi, Parisa Shooshtari, Kaitlin E Samocha, Mark J Daly, Chris Cotsapas
doi: https://doi.org/10.1101/017277
Jinmyung Choi
1Department of Neurology, Yale School of Medicine, New Haven CT, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Parisa Shooshtari
1Department of Neurology, Yale School of Medicine, New Haven CT, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kaitlin E Samocha
2Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
3Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
4Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
5Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark J Daly
2Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
3Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
4Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chris Cotsapas
1Department of Neurology, Yale School of Medicine, New Haven CT, USA
2Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
3Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
4Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
6Department of Genetics, Yale School of Medicine, New Haven CT, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Using robust, integrated analysis of multiple genomic datasets, we show that genes depleted for non-synonymous de novo mutations form a subnetwork of 72 members under strong selective constraint. We further show this subnetwork is preferentially expressed in the early development of the human hippocampus and is enriched for genes mutated in neurological, but not other, Mendelian disorders. We thus conclude that carefully orchestrated developmental processes are under strong constraint in early brain development, and perturbations caused by mutation have adverse outcomes subject to strong purifying selection. Our findings demonstrate that selective forces can act on groups of genes involved in the same process, supporting the notion that adaptation can act coordinately on multiple genes. Our approach provides a statistically robust, interpretable way to identify the tissues and developmental times where groups of disease genes are active. Our findings highlight the importance of considering the interactions between genes when analyzing genome-wide sequence data.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted March 29, 2015.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Network analysis of genome-wide selective constraint reveals a gene network active in early fetal brain intolerant of mutation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Network analysis of genome-wide selective constraint reveals a gene network active in early fetal brain intolerant of mutation
Jinmyung Choi, Parisa Shooshtari, Kaitlin E Samocha, Mark J Daly, Chris Cotsapas
bioRxiv 017277; doi: https://doi.org/10.1101/017277
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Network analysis of genome-wide selective constraint reveals a gene network active in early fetal brain intolerant of mutation
Jinmyung Choi, Parisa Shooshtari, Kaitlin E Samocha, Mark J Daly, Chris Cotsapas
bioRxiv 017277; doi: https://doi.org/10.1101/017277

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3506)
  • Biochemistry (7348)
  • Bioengineering (5324)
  • Bioinformatics (20266)
  • Biophysics (10020)
  • Cancer Biology (7744)
  • Cell Biology (11306)
  • Clinical Trials (138)
  • Developmental Biology (6437)
  • Ecology (9954)
  • Epidemiology (2065)
  • Evolutionary Biology (13325)
  • Genetics (9361)
  • Genomics (12587)
  • Immunology (7702)
  • Microbiology (19027)
  • Molecular Biology (7444)
  • Neuroscience (41049)
  • Paleontology (300)
  • Pathology (1230)
  • Pharmacology and Toxicology (2138)
  • Physiology (3161)
  • Plant Biology (6861)
  • Scientific Communication and Education (1273)
  • Synthetic Biology (1897)
  • Systems Biology (5313)
  • Zoology (1089)