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Genetic linkage analysis in the presence of germline mosaicism. (English) Zbl 1296.92174

Summary: Germline mosaicism is a genetic condition in which some germ cells of an individual contain a mutation. This condition violates the assumptions underlying classic genetic analysis and may lead to failure of such analysis. In this work we extend the statistical model used for genetic linkage analysis in order to incorporate germline mosaicism. We develop a likelihood ratio test for detecting whether a genetic trait has been introduced into a pedigree by germline mosaicism. We analyze the statistical properties of this test and evaluate its performance via computer simulations. We demonstrate that genetic linkage analysis has high power to identify linkage in the presence of germline mosaicism when our extended model is used. We further use this extended model to provide solid statistical evidence that the MDN syndrome studied by M. Genzer-Nir et al. [“Mammary-digital-nail (MDN) syndrome: a novel phenotype maps to human chrmosome 22q12.3-13.1”, Eur. J. Human Genetics 18, No. 6, 662–667 (2010)] has been introduced by germline mosaicism.

MSC:

92D10 Genetics and epigenetics
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