Parent of origin, mosaicism, and recurrence risk: probabilistic modeling explains the broken symmetry of transmission genetics.

ABSTRACT: Most new mutations are observed to arise in fathers, and increasing paternal age positively correlates with the risk of new variants. Interestingly, new mutations in X-linked recessive disease show elevated familial recurrence rates. In male offspring, these mutations must be inherited from mothers. We previously developed a simulation model to consider parental mosaicism as a source of transmitted mutations. In this paper, we extend and formalize the model to provide analytical results and flexible formulas. The results implicate parent of origin and parental mosaicism as central variables in recurrence risk. Consistent with empirical data, our model predicts that more transmitted mutations arise in fathers and that this tendency increases as fathers age. Notably, the lack of expansion la

SUBMITTER: Campbell IM 

PROVIDER: S-EPMC4185125 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature