STATISTICAL-MODELS FOR TRISOMIC PHENOTYPES

Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on t he trisomic chromosome. As with all aneuploid syndromes, however, a co nsiderable degree of variation exists within each phenotype so that an y given trait is present only among a subset of the trisomic populatio n. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for su ch traits. The mapping strategy does not depend on the simple model bu t works in theory under any model that predicts that affected individu als have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by inv estigating what kinds of models give an expected increase in disomic h omozygosity. We describe a number of basic statistical models for tris omic phenotypes. Some of these are logical extensions of standard mode ls for disomic phenotypes, and some are more specific to trisomy. Wher e possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait, Finall y, we determine the sample sizes required to identify the increased di somic homozygosity under each model. Most of the models we explore yie ld detectable increases in disomic homozygosity for some reasonable ra nge of parameter values, usually corresponding to smaller trait freque ncies. It therefore appears that our mapping method should be effectiv e for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known.