Genome-wide changes in protein translation efficiency are associated with autism

dc.contributor.authorRogozin, Igor B.
dc.contributor.authorGertz, E. Michael
dc.contributor.authorBaranov, Pavel V.
dc.contributor.authorPoliakov, Eugenia
dc.contributor.authorSchaffer, Alejandro A.
dc.contributor.funderNational Eye Institute
dc.contributor.funderU.S. National Library of Medicine
dc.contributor.funderNational Institutes of Health
dc.date.accessioned2018-09-27T12:08:16Z
dc.date.available2018-09-27T12:08:16Z
dc.date.issued2018
dc.description.abstractWe previously proposed that changes in the efficiency of protein translation are associated with autism spectrum disorders (ASDs). This hypothesis connects environmental factors and genetic factors because each can alter translation efficiency. For genetic factors, we previously tested our hypothesis using a small set of ASD-associated genes, a small set of ASD-associated variants, and a statistic to quantify by how much a single nucleotide variant (SNV) in a protein coding region changes translation speed. In this study, we confirm and extend our hypothesis using a published set of 1,800 autism quartets (parents, one affected child and one unaffected child) and genome-wide variants. Then, we extend the test statistic to combine translation efficiency with other possibly relevant variables: ribosome profiling data, presence/absence of CpG dinucleotides, and phylogenetic conservation. The inclusion of ribosome profiling abundances strengthens our results for male–male sibling pairs. The inclusion of CpG information strengthens our results for female–female pairs, giving an insight into the significant gender differences in autism incidence. By combining the single-variant test statistic for all variants in a gene, we obtain a single gene score to evaluate how well a gene distinguishes between affected and unaffected siblings. Using statistical methods, we compute gene sets that have some power to distinguish between affected and unaffected siblings by translation efficiency of gene variants. Pathway and enrichment analysis of those gene sets suggest the importance of Wnt signaling pathways, some other pathways related to cancer, ATP binding, and ATP-ase pathways in the etiology of ASDs.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationRogozin, I. B., Gertz, E. M., Baranov, P. V., Poliakov, E. and Schaffer, A. A. (2018) 'Genome-wide changes in protein translation efficiency are associated with autism', Genome Biology and Evolution, 10(8), pp. 1902-1919. doi:10.1093/gbe/evy146en
dc.identifier.doi10.1093/gbe/evy146
dc.identifier.endpage1919
dc.identifier.issn1759-6653
dc.identifier.issued8
dc.identifier.journaltitleGenome Biology and Evolutionen
dc.identifier.startpage1902
dc.identifier.urihttps://hdl.handle.net/10468/6931
dc.identifier.volume10
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urihttps://academic.oup.com/gbe/article/10/8/1902/5050464
dc.rights© 2018, the Authors. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAutism spectrum disorderen
dc.subjectRibosome profilingen
dc.subjectCodon usageen
dc.subjectExpressionen
dc.subjectCpG dinucleotidesen
dc.subjectSingle nucleotide varianten
dc.titleGenome-wide changes in protein translation efficiency are associated with autismen
dc.typeArticle (peer-reviewed)en
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