Parametric and non-parametric linkage analysis of several candidate regions for genes for human handedness.

The frequency of left-handedness in the general population is around 11%. Both environmental and genetic models have been proposed to explain the aetiology of human handedness. The majority of genetic models, such as those of Annett, McManus and Klar, propose a single gene determinant with a non-Mendelian inheritance pattern. As left-handedness is correlated with cerebral asymmetry and is a feature of left-right asymmetry, genes involved in the development of left-right asymmetry can be considered as candidate genes. Candidate gene analysis was performed using an informative extended pedigree, and also using nuclear families of right-handed parents with left-handed children. Segregation analysis in the extended pedigree identified allele sharing in the NODAL and DNAHC13 candidate regions on chromosome 10 and 1. Linkage analysis using the models of Klar and McManus, and non-parametric analysis on nuclear families, subsequently excluded all candidate regions tested. This demonstrates the power to identify the genes specifying handedness by the conduct of extended genetic studies on these and similar cohorts.