Abstract
Handedness is the most pronounced behavioral asymmetry in humans. Genome-wide association studies have largely failed to identify genetic loci associated with phenotypic variance in handedness, supporting the idea that the trait is determined by a multitude of small, possibly interacting genetic and non-genetic influences. However, these studies typically are not capable of detecting influences of rare mutations on handedness. Here, we used whole exome sequencing in a Turkish family with history of consanguinity and overrepresentation of left-handedness and performed quantitative trait analysis with handedness lateralization quotient as a phenotype. While rare variants on different loci showed significant association with the phenotype, none was functionally relevant for handedness. This finding was further confirmed by gene ontology group analysis. Taken together, our results add further evidence to the suggestion that there is no major gene or mutation that causes left-handedness.
Highlights
Handedness is a heritable trait [1] and, historically, it was thought that left-handedness was determined by a major gene effect [2]
All nine family members investigated were left-handed according to EHI results
Analysis of pegboard data showed that seven family members showed superior left hand skill and two family members slightly superior right hand skills
Summary
Handedness is a heritable trait [1] and, historically, it was thought that left-handedness was determined by a major gene effect [2]. This idea was based on the statistical distribution of the phenotype, but has since been refuted by molecular studies. A number of contributing loci have been identified by GWAS and candidate gene studies using handedness questionnaires or hand skill tests like the pegboard test as phenotypes, e.g., LRRTM1, PCSK6 and AR [9,10,11,12,13,14,15].
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