Functional prediction of nsSNPs in the human genome

HERNÁN DOPAZO, & JOAQUÍN DOPAZO

Oviedo, España

Congreso; XXXII Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM); 2009

Sociedad Española de Bioquímica y Biología Molecular

Functional prediction of nsSNPs in the human genome Hernán Dopazo & Joaquín Dopazo Comparative Genomics Unit. Bioinformatics & Genomics Department Centro de Investigación Príncipe Felipe (CIPF). Valencia. Since the earlier works of J. B. S. Haldane on sickle-cell anemia, biologists recognize the power of natural selection on genetic variation and its association to human diseases. In this talk, we will overview many of the main methods developed to predict the functional properties of nsSNPs in the human genome (Dopazo, 2008). WeI will insist that most of these methods are based on features derived from protein structures and/or the evolutionary conservation which represent proxies in order to infer its cost on fitness. Next, we will focus on the measure and description of the selective constraints associated to nsSNPs in the human genome as a direct way to search for selective pressures acting at the codon level. Using maximum likelihood models to estimate the ratio (ω) of nonsynonymous to synonymous rates of substitutions Arbiza et al, (2006) introduced, and Capriotti et al, (2007) extend, an explicit evolutionary measure of selective pressures at a codon level as a direct functional predictor of nsSNPs. We found that codons with ω