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dc.contributor.authorAmos, William
dc.contributor.authorFlint, Jonathan
dc.contributor.authorXu, Xin
dc.date.accessioned2010-11-16T15:22:58Z
dc.date.issued2008
dc.identifier.citationAmos, William, Jonathan Flint, and Xin Xu. 2008. Heterozygosity increases microsatellite mutation rate, linking it to demographic history. BMC Genetics 9:72.en_US
dc.identifier.issn1471-2156en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4556381
dc.description.abstractBackground: Biochemical experiments in yeast suggest a possible mechanism that would cause heterozygous sites to mutate faster than equivalent homozygous sites. If such a process operates, it could undermine a key assumption at the core of population genetic theory, namely that mutation rate and population size are indpendent, because population expansion would increase heterozygosity that in turn would increase mutation rate. Here we test this hypothesis using both direct counting of microsatellite mutations in human pedigrees and an analysis of the relationship between microsatellite length and patterns of demographically-induced variation in heterozygosity. Results: We find that microsatellite alleles of any given length are more likely to mutate when their homologue is unusually different in length. Furthermore, microsatellite lengths in human populations do not vary randomly, but instead exhibit highly predictable trends with both distance from Africa, a surrogate measure of genome-wide heterozygosity, and modern population size. This predictability remains even after statistically controlling for non-independence due to shared ancestry among populations. Conclusion: Our results reveal patterns that are unexpected under classical population genetic theory, where no mechanism exists capable of linking allele length to extrinsic variables such as geography or population size. However, the predictability of microsatellite length is consistent with heterozygote instability and suggest that this has an important impact on microsatellite evolution. Whether similar processes impact on single nucleotide polymorphisms remains unclear.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1471-2156-9-72en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615044/pdf/en_US
dash.licenseLAA
dc.titleHeterozygosity Increases Microsatellite Mutation Rate, Linking it to Demographic Historyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Geneticsen_US
dash.depositing.authorXu, Xin
dc.date.available2010-11-16T15:22:58Z
dash.affiliation.otherSPH^Environmental+Occupational Medicine+Epien_US
dc.identifier.doi10.1186/1471-2156-9-72*
dash.contributor.affiliatedXu, Xin


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