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dc.contributor.authorLu, H-Cen_US
dc.contributor.authorChung, SSen_US
dc.contributor.authorFornili, Aen_US
dc.contributor.authorFraternali, Fen_US
dc.date.accessioned2016-01-12T11:37:59Z
dc.date.available2015-07-29en_US
dc.date.issued2015en_US
dc.identifier.issn2296-889Xen_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/10431
dc.description.abstractIntegration of protein structural information with human genetic variation and pathogenic mutations is essential to understand molecular mechanisms associated with the effects of polymorphisms on protein interactions and cellular processes. We investigate occurrences of non-synonymous SNPs in ordered and disordered protein regions by systematic mapping of common variants and disease-related SNPs onto these regions. We show that common variants accumulate in disordered regions; conversely pathogenic variants are significantly depleted in disordered regions. These different occurrences of pathogenic and common SNPs can be attributed to a negative selection on random mutations in structurally highly constrained regions. New approaches in the study of quantitative effects of pathogenic-related mutations should effectively account for all the possible contexts and relative functional constraints in which the sequence variation occurs.en_US
dc.description.sponsorshipThis research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to FF), the British Heart Foundation (FS/12/41/29724 to AF and FF) and the Leukaemia & Lymphoma Research (to FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship.en_US
dc.format.extent47 - ?en_US
dc.languageengen_US
dc.relation.ispartofFront Mol Bioscien_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.subjectdisease-related mutationsen_US
dc.subjectnon-synonymous SNPsen_US
dc.subjectorder-disorder propensityen_US
dc.subjectprotein disorderen_US
dc.subjectprotein flexibilityen_US
dc.titleAnatomy of protein disorder, flexibility and disease-related mutations.en_US
dc.typeArticle
dc.identifier.doi10.3389/fmolb.2015.00047en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/26322316en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
pubs.volume2en_US
dcterms.dateAccepted2015-07-29en_US


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