Modelling germline mosaicism and different new mutation rates simultaneously for appropriate risk calculations in families with Duchenne muscular dystrophy

Annals of Human Genetics
C FischerT Grimm

Abstract

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic ...Continue Reading

References

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Citations

Aug 8, 2008·The Journal of Heredity·Ronny C Woodruff, Mingcai Zhang
Nov 19, 2013·Genetic Testing and Molecular Biomarkers·Cesárea Bermúdez-LópezMiguel Angel Alcántara-Ortigoza
Jan 29, 2013·Gene·Mariam TajirAbdelaziz Sefiani

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