Figure 1.

Partial Pedigree Showing Mutation Status

Open symbols represent unaffected individuals; filled squares represent affected males and filled circles affected females. Individual generations are numbered with roman numerals on the left. Individuals heterozygous for the p.His306Arg mutation are indicated as N/M. For the LOD-score calculation we assumed a rare autosomal-dominant model with a disease-allele frequency of 0.0001 and phenocopy rate of 0. The mutant DYNC1H1 allele is rare (frequency <0.001); because we only tested affected individuals to avoid issues of predictive testing and variable penetrance and because there are 12 meioses separating the nine sequenced individuals, the LOD score for the variant can be approximated as −log10(0.5¹²) = 3.6.