TY - JOUR
T1 - Functional classification of proteins and protein variants
AU - Lau, Albert Y.
AU - Chasman, Daniel I.
PY - 2004/4/27
Y1 - 2004/4/27
N2 - To help characterize the diversity in biological function of proteins emerging from the analysis of whole genomes, we present an operational definition of biological function that provides an explicit link between the functional classification of proteins and the effects of genetic variation or mutation on protein function. Using phylogenetic information, we establish definite criteria for functional relatedness among proteins and a companion procedure for predicting deleterious alleles or mutations. Applied to the functional classification of sequences similar to 13 human tumor suppressor proteins, our methods predict there are functional properties unique to mammals for three of them, BRCA1, BRCA2, and WT1. We examine protein variants caused by nonsynonymous single-nucleotide polymorphisms in a set of clinically important genes and estimate the magnitude of a disproportionate propensity for disruption of function among the nonsynomous single-nucleotide polymorphisms that are maintained at low frequency in the human population.
AB - To help characterize the diversity in biological function of proteins emerging from the analysis of whole genomes, we present an operational definition of biological function that provides an explicit link between the functional classification of proteins and the effects of genetic variation or mutation on protein function. Using phylogenetic information, we establish definite criteria for functional relatedness among proteins and a companion procedure for predicting deleterious alleles or mutations. Applied to the functional classification of sequences similar to 13 human tumor suppressor proteins, our methods predict there are functional properties unique to mammals for three of them, BRCA1, BRCA2, and WT1. We examine protein variants caused by nonsynonymous single-nucleotide polymorphisms in a set of clinically important genes and estimate the magnitude of a disproportionate propensity for disruption of function among the nonsynomous single-nucleotide polymorphisms that are maintained at low frequency in the human population.
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U2 - 10.1073/pnas.0305043101
DO - 10.1073/pnas.0305043101
M3 - Article
C2 - 15087495
AN - SCOPUS:2342626490
SN - 0027-8424
VL - 101
SP - 6576
EP - 6581
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -