topoSNP: a topographic database of non-synonymous single nucleotide polymorphisms with and without known disease association

The database of topographic mapping of Single Nucleotide Polymorphism (topoSNP) provides an online resource for analyzing non-synonymous SNPs (nsSNPs) that can be mapped onto known 3D structures of proteins. These include disease- associated nsSNPs derived from the Online Mendelian Inheritance in Man (OMIM) database and other nsSNPs derived from dbSNP, a resource at the National Center for Biotechnology Information that catalogs SNPs. TopoSNP further classifies each nsSNP site into three categories based on their geometric location: those located in a surface pocket or an interior void of the protein, those on a convex region or a shallow depressed region, and those that are completely buried in the interior of the protein structure. These unique geometric descriptions provide more detailed mapping of nsSNPs to protein structures. The current release also includes relative entropy of SNPs calculated from multiple sequence alignment as obtained from the Pfam database (a database of protein families and conserved protein motifs) as well as manually adjusted multiple alignments obtained from ClustalW. These structural and conservational data can be useful for studying whether nsSNPs in coding regions are likely to lead to phenotypic changes. TopoSNP includes an interactive structural visualization web interface, as well as downloadable batch data. The database will be updated at regular intervals and can be accessed at: http://gila.bioengr.uic.edu/snp/toposnp.

[1]  P. Bork,et al.  Towards a structural basis of human non-synonymous single nucleotide polymorphisms. , 2000, Trends in genetics : TIG.

[2]  A Yoshida,et al.  Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Henikoff,et al.  Accounting for human polymorphisms predicted to affect protein function. , 2002, Genome research.

[4]  C. Fischer.  Handbook of statistical genetics: , 2002, Human Genetics.

[5]  John P. Huelsenbeck,et al.  MRBAYES: Bayesian inference of phylogenetic trees , 2001, Bioinform..

[6]  S. Kasif,et al.  Structural location of disease-associated single-nucleotide polymorphisms. , 2003, Journal of molecular biology.

[7]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology , 2003, Nucleic Acids Res..

[8]  P. Bork,et al.  Human non-synonymous SNPs: server and survey. , 2002, Nucleic acids research.

[9]  Elizabeth M. Smigielski,et al.  dbSNP: the NCBI database of genetic variation , 2001, Nucleic Acids Res..

[10]  Steven Henikoff,et al.  SIFT: predicting amino acid changes that affect protein function , 2003, Nucleic Acids Res..

[11]  R. Proia,et al.  Synthesis of beta-hexosaminidase in cell-free translation and in intact fibroblasts: an insoluble precursor alpha chain in a rare form of Tay-Sachs disease. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Henikoff,et al.  Predicting deleterious amino acid substitutions. , 2001, Genome research.

[13]  A. Munnich,et al.  In Vitro Splicing Deficiency Induced by a C to T Mutation at Position −3 in the Intron 10 Acceptor Site of the Phenylalanine Hydroxylase Gene in a Patient with Phenylketonuria(*) , 1995, The Journal of Biological Chemistry.

[14]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information: update , 2004, Nucleic acids research.

[15]  Ziheng Yang,et al.  Adaptive Molecular Evolution , 2004, Handbook of Statistical Genomics.

[16]  D. Balding,et al.  Handbook of statistical genetics , 2004 .

[17]  D. Chasman,et al.  Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. , 2001, Journal of molecular biology.

[18]  M. Madera,et al.  A comparison of profile hidden Markov model procedures for remote homology detection. , 2002, Nucleic acids research.