Mouse SNP Miner: an annotated database of mouse functional single nucleotide polymorphisms

To help identify functional DNA sequence variations within quantitative trait loci we have used the Ensembl annotated genome sequence to compile a database of mouse single nucleotide polymorphisms (SNPs) that are predicted to cause missense, nonsense, frameshift, or splice site mutations (available at http://bioinfo.embl.it/SnpApplet/ webcite). For missense mutations we have used the PolyPhen and PANTHER algorithms to predict whether amino acid changes are likely to disrupt protein function.We have developed a database of mouse SNPs predicted to cause missense, nonsense, frameshift, and splice-site mutations. Our analysis revealed that 20% and 14% of missense SNPs are likely to be deleterious according to PolyPhen and PANTHER, respectively, and 6% are considered deleterious by both algorithms. The database also provides gene expression and functional annotations from the Symatlas, Gene Ontology, and OMIM databases to further assess candidate phenotype-causing mutations. To demonstrate its utility, we show that Mouse SNP Miner successfully finds a previously identified candidate SNP in the taste receptor, Tas1r3, that underlies sucrose preference in the C57BL/6J strain. We also use Mouse SNP Miner to derive a list of candidate phenotype-causing mutations within a previously uncharacterized QTL for response to morphine in the 129/Sv strain.The laboratory mouse is a powerful model for studying the genetic determinants of human disease-related phenotypes. One way to study genetic modifiers of such phenotypes is to take advantage of genetic variations existing between mouse inbred strains to map chromosomal regions, or loci, that are associated with quantitative traits, so-called quantitative trait loci (QTL). Over 2,000 QTL are listed in the Mouse Genome Informatics database [1], and many of these are relevant to human disease.However, the identification of causal functional DNA polymorphisms underlying QTL has remained problematic, with such variations having been conv