De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-12

AUTHORS

Bin Xu, Iuliana Ionita-Laza, J Louw Roos, Braden Boone, Scarlet Woodrick, Yan Sun, Shawn Levy, Joseph A Gogos, Maria Karayiorgou

ABSTRACT

To evaluate evidence for de novo etiologies in schizophrenia, we sequenced at high coverage the exomes of families recruited from two populations with distinct demographic structures and history. We sequenced a total of 795 exomes from 231 parent-proband trios enriched for sporadic schizophrenia cases, as well as 34 unaffected trios. We observed in cases an excess of de novo nonsynonymous single-nucleotide variants as well as a higher prevalence of gene-disruptive de novo mutations relative to controls. We found four genes (LAMA2, DPYD, TRRAP and VPS39) affected by recurrent de novo events within or across the two populations, which is unlikely to have occurred by chance. We show that de novo mutations affect genes with diverse functions and developmental profiles, but we also find a substantial contribution of mutations in genes with higher expression in early fetal life. Our results help define the genomic and neural architecture of schizophrenia. More... »

PAGES

1365

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2446

    DOI

    http://dx.doi.org/10.1038/ng.2446

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039601161

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23042115


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