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> Maximum Likelihood Estimation Of Site-specific Mutation Rates In Human Mitochondrial Dna From Partial Phylogenetic Classification, Saharon Rosset et al (2008)
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сообщение 17.9.2008, 10:12
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Saharon Rosset et al - Maximum Likelihood Estimation of Site-Specific Mutation Rates in Human Mitochondrial DNA from Partial Phylogenetic Classification // Genetics doi: 10.1534/genetics.108.091116

Abstract

The mitochondrial DNA hyper-variable segment I (HVS-I) is widely used in studies of human evolutionary genetics, and therefore accurate estimates of mutation rates among nucleotide sites in this region are essential. We have developed a novel maximum-likelihood methodology for estimating site-specific mutation rates from partial phylogenetic information, such as haplogroup association. The resulting estimation problem is a generalized linear model, with a non-standard link function. We develop inference and bias correction tools for our estimates and a hypothesis testing approach for site independence. We demonstrate our methodology using 16,609 HVS-I samples from the Genographic Project. Our results suggest that mutation rates among nucleotide sites in HVS-I are highly variable. The 16,400--16,500 region exhibits significantly lower rates compared to other regions, suggesting potential functional constraints. Several loci identified in the literature as possible termination associated sequences (TAS) do not yield statistically slower rates than the rest of HVS-I, casting doubt on their functional importance. Our tests do not reject the null hypothesis of independent mutation rates among nucleotide sites, supporting the use of site-independence assumption for analyzing HVS-I. Potential extensions of our methodology include its application to estimation of mutation rates in other genetic regions, like Y-chromosome short tandem repeats.

http://www.genetics.org/cgi/content/abstra...cs.108.091116v1
PDF - http://www.genetics.org/cgi/rapidpdf/genetics.108.091116v1
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