To evaluate the significance of potential disease-causing variants, we assessed cosegregation with disease using a method previously described36. We calculated lod scores using a model assuming 100% penetrance of mental retardation–causing variants, variant prevalence of 0.1% and an mental retardation sporadic rate of 1%, using the Genehunter program. An estimate of the proportion of variants that were deleterious was derived by calculating a heterogeneity lod score over all families, assuming that a proportion (alpha) of variants were associated with the disease risk, and maximizing over alpha.
