title: Whole exome sequencing for handedness in a large and highly consanguineous family.
abstract: Pinpointing genes involved in non-right-handedness has the potential to clarify developmental contributions to human brain lateralization. Major-gene models have been considered for human handedness which allow for phenocopy and reduced penetrance, i.e. an imperfect correspondence between genotype and phenotype. However, a recent genome-wide association scan did not detect any common polymorphisms with substantial genetic effects. Previous linkage studies in families have also not yielded significant findings. Genetic heterogeneity and/or polygenicity are therefore indicated, but it remains possible that relatively rare, or even unique, major-genetic effects may be detectable in certain extended families with many non-right-handed members. Here we applied whole exome sequencing to 17 members from a single, large consanguineous family from Pakistan. Multipoint linkage analysis across all autosomes did not yield clear candidate genomic regions for involvement in the trait and single-point analysis of exomic variation did not yield clear candidate mutations/genes. Any genetic contribution to handedness in this unusual family is therefore likely to have a complex etiology, as at the population level.
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
authors.forename: Tulya
authors.initials: T
authors.lastname: Kavaklioglu
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), 24-Mauve Area, G-9/1, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ajmal
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), 24-Mauve Area, G-9/1, Islamabad, Pakistan. Electronic address: ahameed0786@hotmail.com.
authors.forename: Abdul
authors.initials: A
authors.lastname: Hameed
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands. Electronic address: Clyde.Francks@mpi.nl.
authors.forename: Clyde
authors.initials: C
authors.lastname: Francks
mesh_terms: D003241:Consanguinity; D059472:Exome; D005190:Family; D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D008040:Genetic Linkage; D014644:Genetic Variation; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010154:Pakistan; D010375:Pedigree
keywords: Asymmetry; Consanguineous; Exome sequencing; Handedness; Linkage