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A phylogenetic approach to assessing the significance of missense mutations in disease genes

Item Type:Article
Title:A phylogenetic approach to assessing the significance of missense mutations in disease genes
Creators Name:Koref, M.E.S. and Gangeswaran, R. and Koref, I.P.S. and Shanahan, N. and Hancock, J.M.
Abstract:The identification of deleterious mutations within candidate genes is a crucial step in the elucidation of the genetic bases of human disease. However, the significance of any base or amino acid change within a gene is unknown until detailed structural and functional analysis has been carried out. A potentially rapid way of identifying functionally important sites within a gene is to identify evolutionarily conserved regions. Mutations affecting such sites are assumed to be deleterious for the carrier. In this communication we generalize this approach and present a formal framework to assess whether a specific mutation is deleterious given sequence data from a set of homologues. We propose a score that takes into account the nature of the mutation, the conservation of the affected residue among the different species, and their phylogenetic relationships. Its performance is examined using published TP53 mutations and frequent polymorphic variants.
Keywords:Evolution, Inherited Disease, Mutation Analysis, P53, TP53
Source:Human Mutation
ISSN:1059-7794
Publisher:Wiley (U.K.)
Volume:22
Number:1
Page Range:51-58
Date:July 2003
Official Publication:https://doi.org/10.1002/humu.10235
PubMed:View item in PubMed

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