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Heterogeneous mutation processes in human microsatellite DNA sequences


Although microsatellite polymorphisms are one of the most commonly used tools in genetic analyses1,2,3, it remains to be understood how microsatellite DNA has evolved as a ubiquitous and highly abundant class of repetitive sequences in eukaryotic genomes4. On the basis of analyses of spontaneous human microsatellite mutations of germline origin, I show here that different mutation biases underlie the evolution of microsatellite repeats. The within-locus mutation rate increases with allele length, but is not affected by the size difference between an individual's two alleles (allele span). Within loci, long alleles tend to mutate to shorter lengths, thereby acting to prevent infinite growth. Expansions are more common than contractions among dinucleotide repeats, whereas no such trend is evident among tetranucleotide repeats. This observation is consistent with the longer repeat lengths and higher frequency of di- compared with tetranucleotide repeats. An excess of paternally transmitted mutations (male-to-female ratio of 4.9) supports a male-biased mutation rate in the human genome.

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Figure 1: The number of human germline microsatellite mutations in relation to standardized allele size.
Figure 2: Size and direction (magnitude) of human germline microsatellite mutations.
Figure 3: Number of repeat units in mutating human microsatellite alleles.
Figure 4: Size and direction (magnitude) of human germline microsatellite mutations in relation to standardized allele size.

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I thank B. Sheldon for discussions and comments on the manuscript, and P. Gunn, B. Rolf and P. Stapleton for data on microsatellite mutations. Financial support was obtained from the Swedish Research Councils for Agriculture and Forestry, for Natural Sciences and for Medicine.

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Correspondence to Hans Ellegren.

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Ellegren, H. Heterogeneous mutation processes in human microsatellite DNA sequences. Nat Genet 24, 400–402 (2000).

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