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Methods Mol Biol. 2009;573:189-212. doi: 10.1007/978-1-60761-247-6_11.

Computing genetic imprinting expressed by haplotypes.

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Department of Statistics, University of Florida, Gainesville, FL, USA.


Different expression of maternally and paternally inherited alleles at certain genes is called genetic imprinting. Despite its great importance in trait formation, development, and evolution, it remains unclear how genetic imprinting operates in a complex network of interactive genes located throughout the genome. Genetic mapping has proven to be a powerful tool that can estimate the distribution and effects of imprinted genes. While traditional mapping models attempt to detect imprinted quantitative trait loci based on a linkage map constructed from molecular markers, we have developed a statistical model for estimating the imprinting effects of haplotypes composed of multiple sequenced single-nucleotide polymorphisms. The new model provides a characterization of the difference in the effect of maternally and paternally derived haplotypes, which can be used as a tool for genetic association studies at the candidate gene or genome-wide level. The model was used to map imprinted haplotype effects on body mass index in a random sample from a natural human population, leading to the detection of significant imprinted effects at the haplotype level. The new model will be useful for characterizing the genetic architecture of complex quantitative traits at the nucleotide level.

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