Counseling for dominant traits: a correction for the ascertainment bias due to referral for analysis

Genetic heterogeneity complicates genetic counseling because the correct mode of inheritance must be determined independently for each pedigree. When autosomal and X-linked dominants inheritance mechanisms are known, as for example with retinitis pigmentosa, then only families where male-to-male transmission is observed may be readily counseled. The other pedigrees may be autosomal but lack male-to-male transmission due to chance segregation. Since only the pedigrees without male-to-male transmission are analyzed for their mode of inheritance, there is an ascertainment bias which must be corrected when evaluating the likelihood of the two inheritance patterns. A method to correct for this bias using conditional likelihoods is given, along with examples to demonstrate its use.