Identification and analysis of deleterious human SNPs.
We have developed two methods of identifying which non-synonomous single base changes have a deleterious effect on protein function in vivo. One method, described elsewhere, analyzes the effect of the resulting amino acid change on protein stability, utilizing structural information. The other method, introduced here, makes use of the conservation and type of residues observed at a base change position within a protein family. A machine learning technique, the support vector machine, is trained on single amino acid changes that cause monogenic disease, with a control set of amino acid changes fixed between species. Both methods are used to identify deleterious single nucleotide polymorphisms (SNPs) in the human population. After carefully controlling for errors, we find that approximately one quarter of known non-synonymous SNPs are deleterious by these criteria, providing a set of possible contributors to human complex disease traits.
Yue
Peng
P
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville MD 20850, USA.
Moult
John
J
D000818:Animals; D004252:DNA Mutational Analysis; D030562:Databases, Protein; D019143:Evolution, Molecular; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D012680:Sensitivity and Specificity
D011506:Proteins