Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology

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  • dc.contributor.author Spataro, Nino, 1984-ca
  • dc.contributor.author Rodríguez, Juan Antonioca
  • dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-ca
  • dc.contributor.author Bosch Fusté, Elenaca
  • dc.date.accessioned 2017-07-04T07:59:04Z
  • dc.date.available 2017-07-04T07:59:04Z
  • dc.date.issued 2017
  • dc.description.abstract Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevant implications when designing mapping strategies in future genetic studies. Here we show that, relative to non-disease genes, human disease (HD) genes have specific evolutionary profiles and protein network properties. Additionally, our results indicate that the mutation-selection balance renders an insufficient account of the evolutionary history of some HD genes and that adaptive selection could also contribute to shape their genetic architecture. Notably, several biological features of HD genes depend on the type of pathology (complex or Mendelian) with which they are related. For example, genes harbouring both causal variants for Mendelian disorders and risk factors for complex disease traits (Complex-Mendelian genes), tend to present higher functional relevance in the protein network and higher expression levels than genes associated only with complex disorders. Moreover, risk variants in Complex-Mendelian genes tend to present higher odds ratios than those on genes associated with the same complex disorders but with no link to Mendelian diseases. Taken together, our results suggest that genetic variation at genes linked to Mendelian disorders plays an important role in driving susceptibility to complex disease.
  • dc.description.sponsorship This work was supported by Ministerio de Ciencia e Innovación, Spain (SAF2011-29239 to EB and BFU2012-38236 to AN), by Direcció General de Recerca, Generalitat de Catalunya (2014SGR1311 and 2014SGR866), by the Spanish National Institute of Bioinfomatics of the Instituto de Salud Carlos III (PT13/0001/0026) and by FEDER (Fondo Europeo de Desarrollo Regional)/FSE (Fondo Social Europeo). Funding to pay the Open Access publication charges for this article was provided by the ICREA Award granted to EB by the Institució Catalana de Recerca i Estudis Avançats (Generalitat de Catalunya).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Spataro N, Rodríguez JA, Navarro i Cuartiellas A, Bosch Fusté E. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology. Human Molecular Genetics. 2017;26(3):489-500. DOI: 10.1093/hmg/ddw405
  • dc.identifier.doi http://dx.doi.org/10.1093/hmg/ddw405
  • dc.identifier.issn 0964-6906
  • dc.identifier.uri http://hdl.handle.net/10230/32497
  • dc.language.iso eng
  • dc.publisher Oxford University Pressca
  • dc.relation.ispartof Human Molecular Genetics. 2017;26(3):489-500
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29239
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-38236
  • dc.rights © The Author 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Genes
  • dc.subject.keyword Mendelian disorders
  • dc.title Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiologyca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Departament de Medicina i Ciències de la Vida)
Articles (Center for Genomic Regulation (CRG))