Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Sep 1;30(17):3894-900.
doi: 10.1093/nar/gkf493.

Human non-synonymous SNPs: server and survey

Vasily Ramensky  1 , Peer Bork, Shamil Sunyaev
Affiliations

Human non-synonymous SNPs: server and survey

Vasily Ramensky et al. Nucleic Acids Res. .

Abstract

Human single nucleotide polymorphisms (SNPs) represent the most frequent type of human population DNA variation. One of the main goals of SNP research is to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. Non-synonymous coding SNPs (nsSNPs) comprise a group of SNPs that, together with SNPs in regulatory regions, are believed to have the highest impact on phenotype. Here we present a World Wide Web server to predict the effect of an nsSNP on protein structure and function. The prediction method enabled analysis of the publicly available SNP database HGVbase, which gave rise to a dataset of nsSNPs with predicted functionality. The dataset was further used to compare the effect of various structural and functional characteristics of amino acid substitutions responsible for phenotypic display of nsSNPs. We also studied the dependence of selective pressure on the structural and functional properties of proteins. We found that in our dataset the selection pressure against deleterious SNPs depends on the molecular function of the protein, although it is insensitive to several other protein features considered. The strongest selective pressure was detected for proteins involved in transcription regulation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
PolyPhen query processing flowchart. PolyPhen combines information on sequence features, multiple alignment with homologous proteins and structural parameters and contacts to make a prediction of nsSNP effect on protein function. hs_swall is the abbreviation for the Homo sapiens subset of the SWALL database (also known as SPTR, i.e. SwissProt + TrEMBL). Var1,2, two amino acid variants; ACC/ID, SWALL accession number or ID.
Figure 2
Figure 2
Results of the PolyPhen analysis of the HGVbase database v.12. hs_swall denotes the Homo sapiens subset of the SWALL database. snp2prot is an in-house command line tool to map HGVbase SNPs onto sequences of known human proteins. 11 152 nsSNPs were identified. 1591 of them have been predicted as possibly damaging for protein structure and function and an additional 1257 as probably damaging. The number of structure-based predictions is much lower compared with the number of sequence-based predictions because structural information was available in only 1026 cases.
See this image and copyright information in PMC

References

    1. Risch N. and Merikangas,K. (1996) The future of genetic studies of complex human diseases. Science, 273, 1516–1517. - PubMed
    1. Risch N.J. (2000) Searching for genetic determinants in the new millennium. Nature, 15, 847–856. - PubMed
    1. Lai E., Riley,J., Purvis,I. and Roses,A. (1998) A 4-Mb high-density single nucleotide polymorphism-based map around human APOE. Genomics, 54, 31–38. - PubMed
    1. Emahazion T., Feuk,L., Jobs,M., Sawyer,S.L., Fredman,D., St Clair,D., Prince,J.A. and Brookes,A.J. (2001) SNP association studies in Alzheimer’s disease highlight problem for complex disease analysis. Trends Genet., 17, 407–413. - PubMed
    1. Schork N.J., Fallin,D. and Lanchbury,J.S. (2000) Single nucleotide polymorphisms and the future of genetic epidemiology. Clin. Genet., 58, 250–264. - PubMed