Accounting for Human Polymorphisms Predicted to Affect Protein Function

  1. Pauline C. Ng1,2 and
  2. Steven Henikoff1,3,4
  1. 1Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; 2Department of Bioengineering, University of Washington, Seattle, Washington 98105, USA; 3Howard Hughes Medical Institute, Seattle, Washington 98109, USA

Abstract

A major interest in human genetics is to determine whether a nonsynonymous single-base nucleotide polymorphism (nsSNP) in a gene affects its protein product and, consequently, impacts the carrier's health. We used the SIFT (Sorting Intolerant From Tolerant) program to predict that 25% of 3084 nsSNPs from dbSNP, a public SNP database, would affect protein function. Some of the nsSNPs predicted to affect function were variants known to be associated with disease. Others were artifacts of SNP discovery. Two reports have indicated that there are thousands of damaging nsSNPs in an individual's human genome; we find the number is likely to be much lower.

Footnotes

  • 4 Corresponding author.

  • E-MAIL steveh{at}fhcrc.org; FAX (206) 667-5889.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.212802.

    • Received August 27, 2001.
    • Accepted December 20, 2001.
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