Jul 26, 2011

Ranking insertion, deletion and nonsense mutations based on their effect on genetic information

BMC Bioinformatics
Amin Zia, Alan M Moses

Abstract

Genetic variations contribute to normal phenotypic differences as well as diseases, and new sequencing technologies are greatly increasing the capacity to identify these variations. Given the large number of variations now being discovered, computational methods to prioritize the functional importance of genetic variations are of growing interest. Thus far, the focus of computational tools has been mainly on the prediction of the effects of amino acid changing single nucleotide polymorphisms (SNPs) and little attention has been paid to indels or nonsense SNPs that result in premature stop codons. We propose computational methods to rank insertion-deletion mutations in the coding as well as non-coding regions and nonsense mutations. We rank these variations by measuring the extent of their effect on biological function, based on the assumption that evolutionary conservation reflects function. Using sequence data from budding yeast and human, we show that variations which that we predict to have larger effects segregate at significantly lower allele frequencies, and occur less frequently than expected by chance, indicating stronger purifying selection. Furthermore, we find that insertions, deletions and premature stop codons asso...Continue Reading

Mentioned in this Paper

TP53 gene
Transcription Repressor/Corepressor
Mutation, Nonsense
Exons
Saccharomyces cerevisiae allergenic extract
Medical Genetics Specialty
Amino Acids, I.V. solution additive
Pseudo brand of pseudoephedrine
Codon, Terminator
Neoplasms

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