The Cancer Genome Anatomy Project's Genetic Annotation I

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As part of the National Cancer Institute's Cancer Genome Anatomy Project (CGAP), the Genetic Annotation Initiative (GAI) seeks to expand the collection of gene-based genetic analysis reagents for cancer research. We have identified more than 30,000 high-probability candidate single nucleotide polymorphisms (SNPs) by analyzing publicly available expressed sequence tag chromatograms with a set of sequence analysis tools. This approach has also been applied to identify more than 16,000 candidate SNPs in the mouse. Using pooled DNA from 92 unrelated individuals and MALDI-TOF mass spectrometry, we have validated more than 7,000 human SNPs. To present the genetic variants in a format useful for the human genetics community we have constructed an integrated genetic/physical SNP map. Genetic map positions of reference markers are from the the CHLC/ABI version 1 linkage map; physical map positions are from the GeneMap'98 Genebridge4 radiation hybrid map. Tissue-specific and cancer-specific views of these maps are also available. These maps permit the selection of SNPs for genes with specific expression patterns. Through related CGAP infrastructure it is also possible to view the SNP data in other biologically relevant contexts. The Gene Ontology browser enables users to identify genes by biological process, cellular component or molecular function. Other CGAP tools allow the visualization of biochemical pathways. We have integrated our SNP discovery efforts with those from other workers to give a comprehensive view of gene-based SNPs. We provide a browser that shows the location of polymorphisms in mRNA sequences and indicates whether variants cause amino acid substitutions. Coding regions and conserved protein motifs from the Pfam database are also displayed in the browser. If a SNP alters an amino acid in a conserved protein domain, we assess how the amino acid substitution affects the fit of the protein to the motif model. The integrated maps, a Java-based tool for viewing candidate SNPs in the context of EST assemblies, reagent information (including PCR primers and extension primers), and a SNP search engine are available at our website: http://lpgws.nci.nih.gov/GAI/. We provide access to our SNP detection software for non-commercial use.