Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes

Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes

Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the...

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Main Authors: Guipponi, Michel, Santoni, Federico A., Setola, Vincent, Gehrig, Corinne, Rotharmel, Maud, Cuenca, Macarena, Guillin, Olivier, Dikeos, Dimitris, Georgantopoulos, Georgios, Papadimitriou, George, Curtis, Logos, Méary, Alexandre, Schürhoff, Franck, Jamain, Stéphane, Avramopoulos, Dimitri, Leboyer, Marion, Rujescu, Dan, Pulver, Ann, Campion, Dominique, Siderovski, David P., Antonarakis, Stylianos E.
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242613/
id pubmed-4242613
recordtype oai_dc
spelling pubmed-42426132014-11-26 Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes Guipponi, Michel Santoni, Federico A. Setola, Vincent Gehrig, Corinne Rotharmel, Maud Cuenca, Macarena Guillin, Olivier Dikeos, Dimitris Georgantopoulos, Georgios Papadimitriou, George Curtis, Logos Méary, Alexandre Schürhoff, Franck Jamain, Stéphane Avramopoulos, Dimitri Leboyer, Marion Rujescu, Dan Pulver, Ann Campion, Dominique Siderovski, David P. Antonarakis, Stylianos E. Research Article Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7×10−8 per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene. Public Library of Science 2014-11-24 /pmc/articles/PMC4242613/ /pubmed/25420024 http://dx.doi.org/10.1371/journal.pone.0112745 Text en © 2014 Guipponi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Guipponi, Michel
Santoni, Federico A.
Setola, Vincent
Gehrig, Corinne
Rotharmel, Maud
Cuenca, Macarena
Guillin, Olivier
Dikeos, Dimitris
Georgantopoulos, Georgios
Papadimitriou, George
Curtis, Logos
Méary, Alexandre
Schürhoff, Franck
Jamain, Stéphane
Avramopoulos, Dimitri
Leboyer, Marion
Rujescu, Dan
Pulver, Ann
Campion, Dominique
Siderovski, David P.
Antonarakis, Stylianos E.
spellingShingle Guipponi, Michel
Santoni, Federico A.
Setola, Vincent
Gehrig, Corinne
Rotharmel, Maud
Cuenca, Macarena
Guillin, Olivier
Dikeos, Dimitris
Georgantopoulos, Georgios
Papadimitriou, George
Curtis, Logos
Méary, Alexandre
Schürhoff, Franck
Jamain, Stéphane
Avramopoulos, Dimitri
Leboyer, Marion
Rujescu, Dan
Pulver, Ann
Campion, Dominique
Siderovski, David P.
Antonarakis, Stylianos E.
Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes
author_facet Guipponi, Michel
Santoni, Federico A.
Setola, Vincent
Gehrig, Corinne
Rotharmel, Maud
Cuenca, Macarena
Guillin, Olivier
Dikeos, Dimitris
Georgantopoulos, Georgios
Papadimitriou, George
Curtis, Logos
Méary, Alexandre
Schürhoff, Franck
Jamain, Stéphane
Avramopoulos, Dimitri
Leboyer, Marion
Rujescu, Dan
Pulver, Ann
Campion, Dominique
Siderovski, David P.
Antonarakis, Stylianos E.
author_sort Guipponi, Michel
title Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes
title_short Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes
title_full Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes
title_fullStr Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes
title_full_unstemmed Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes
title_sort exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes
description Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7×10−8 per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242613/
_version_ 1613160252962766848

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