Accounting for Human Polymorphisms Predicted to Affect Protein Function

Pauline C. Ng; Steven Henikoff

doi:10.1101/gr.212802

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.

Keywords

dbSNPBiologySingle-nucleotide polymorphismGeneticsNonsynonymous substitutionSNPAffect (linguistics)Human genomeGeneGenomeComputational biologyGenotype

Affiliated Institutions

Related Publications

SIFT: predicting amino acid changes that affect protein function

P.C. Ng

Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to ...

2003 Nucleic Acids Research 6603 citations

Human non-synonymous SNPs: server and survey

Vasily Ramensky

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 genet...

2002 Nucleic Acids Research 2284 citations

Predicting the Effects of Amino Acid Substitutions on Protein Function

Pauline C. Ng , Steven Henikoff

Nonsynonymous single nucleotide polymorphisms (nsSNPs) are coding variants that introduce amino acid changes in their corresponding proteins. Because nsSNPs can affect protein f...

2006 Annual Review of Genomics and Human G... 974 citations

SIFT web server: predicting effects of amino acid substitutions on proteins

Ngak-Leng Sim , P. Naresh Kumar , Jing Hu +3 more

The Sorting Intolerant from Tolerant (SIFT) algorithm predicts the effect of coding variants on protein function. It was first introduced in 2001, with a corresponding website t...

2012 Nucleic Acids Research 2357 citations

Predicting Deleterious Amino Acid Substitutions

Pauline C. Ng , Steven Henikoff

Many missense substitutions are identified in single nucleotide polymorphism (SNP) data and large-scale random mutagenesis projects. Each amino acid substitution potentially aff...

2001 Genome Research 2643 citations

Publication Info

Year: 2002
Type: article
Volume: 12
Issue: 3
Pages: 436-446
Citations: 700
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

Accounting for Human Polymorphisms Predicted to Affect Protein Function

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

700

OpenAlex

Cite This

APA Style

                            
                                    Pauline C. Ng, 
                                
                                    Steven Henikoff
                                
                            (2002). 
                            Accounting for Human Polymorphisms Predicted to Affect Protein Function. 
                            Genome Research
                            , 12
                            (3)
                            , 436-446.
                            https://doi.org/10.1101/gr.212802

Identifiers

DOI: 10.1101/gr.212802