dc.contributor.author | Lu, H-C | en_US |
dc.contributor.author | Chung, SS | en_US |
dc.contributor.author | Fornili, A | en_US |
dc.contributor.author | Fraternali, F | en_US |
dc.date.accessioned | 2016-01-12T11:37:59Z | |
dc.date.available | 2015-07-29 | en_US |
dc.date.issued | 2015 | en_US |
dc.identifier.issn | 2296-889X | en_US |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/10431 | |
dc.description.abstract | Integration 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.sponsorship | This 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.extent | 47 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Front Mol Biosci | en_US |
dc.rights | This 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.subject | disease-related mutations | en_US |
dc.subject | non-synonymous SNPs | en_US |
dc.subject | order-disorder propensity | en_US |
dc.subject | protein disorder | en_US |
dc.subject | protein flexibility | en_US |
dc.title | Anatomy of protein disorder, flexibility and disease-related mutations. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.3389/fmolb.2015.00047 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/26322316 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 2 | en_US |
dcterms.dateAccepted | 2015-07-29 | en_US |