Document Type
Article
Publication Date
2014
College/Unit
School of Medicine
Department/Program/Center
Physiology, Pharmacology & Neuroscience
Abstract
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.
Digital Commons Citation
Guipponi, Michel; Santoni, Federico A.; Setola, Vincent; Gehrig, Corinne; Rotharmel, Maud; Cuenca, Macarena; Guillin, Olivier; Dikeos, Dimitris; Georgantopoulos, Georgios; Papadimitriou, George; Curtis, Logos; Meary, Alexandre; Schurhoff, Frank; Jamain, Stephane; Avramopoulos, Dimitri; Leboyer, Marion; Rujescu, Dan; Pulver, Ann; Campion, Dominique; Siderovski, David P.; and Antonarakis, Stylianos E., "Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes" (2014). Faculty & Staff Scholarship. 2486.
https://researchrepository.wvu.edu/faculty_publications/2486
Source Citation
Guipponi M, Santoni FA, Setola V, Gehrig C, Rotharmel M, Cuenca M, et al. (2014) Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes. PLoS ONE 9(11): e112745. https://doi.org/10.1371/journal.pone.0112745
Comments
© 2014 Guipponi et al. 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 credited.