Figure 1.

Under-calling heterozygous genotypes affects de novo detection at a given site. In the top panel, the mother’s genotype is called AA by the sample-independent approach since the binomial probability of sampling once the C allele among 20 reads if the mother is heterozygote is very small. (Nielsen et al., 2011, suggest calling a site homozygous if the minor allele is less than 20%, a rule which we adopt for these examples.) When the family data is considered jointly, identifying a C in the child increases the probability of the AC genotype for the mother, leading to a low probability of de novo mutation at this site. (It is much more likely that the mother’s chromosomes were sampled unevenly, ≈10⁻⁵, than that there is an actual mutation at the site, ≈10⁻⁸.) In the bottom panel, the child’s genotype is called AA. However, given an error rate and the parental coverage, the probability of a de novo mutation at this site is high. The de novo mutation probabilities were computed using the method described here with the following parameters: θ = 0.001, ε = 0.005, μ = μ_s = 2 × 10⁻⁸. (See section 2.1 for a description of these parameters.)