Avtor/Urednik		Santibáñez-Koref, Mauro F.; Gangeswaran, Rathithevy; Santibañez Koref, I. P.; Shanahan, N.; Hancock, John M.
Naslov		A phylogenetic approach to assessing the significance of missense mutations in disease genes
Tip		članek
Vol. in št.		Letnik 22, št. 1
Leto izdaje		2003
Obseg		str. 51-58
ISSN		1059-7794 - Human mutation
Jezik		eng
Abstrakt		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.
Proste vsebinske oznake		analiza mutacij dedna bolezen evolucija mutation analysis inherited disease evolution