Mutation patterns of amino acid tandem repeats in the human proteome.
Abstract
Amino acid tandem repeats are found in nearly one-fifth of human proteins. Abnormal expansion of these regions is associated with several human disorders. To gain further insight into the mutational mechanisms that operate in this type of sequence, we have analyzed a large number of mutation variants derived from human expressed sequence tags (ESTs). We identified 137 polymorphic variants in 115 different amino acid tandem repeats. Of these, 77 contained amino acid substitutions and 60 contained gaps (expansions or contractions of the repeat unit). The analysis showed that at least about 21% of the repeats might be polymorphic in humans. We compared the mutations found in different types of amino acid repeats and in adjacent regions. Overall, repeats showed a five-fold increase in the number of gap mutations compared to adjacent regions, reflecting the action of slippage within the repetitive structures. Gap and substitution mutations were very differently distributed between different amino acid repeat types. Among repeats containing gap variants we identified several disease and candidate disease genes. This is the first report at a genome-wide scale of the types of mutations occurring in the amino acid repeat component of th...Continue Reading
References
A relationship between lengths of microsatellites and nearby substitution rates in mammalian genomes
Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes
Time dependency of molecular rate estimates and systematic overestimation of recent divergence times
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