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Its a question that has spurred many hypotheses over the years. The general consensus in modern science is that right- or left-brain hemisphere dominance dictates our handedness.

Studies of human fetuses have shown that right-lateralized predominance of arm movements can occur as early as 10 weeks into gestation in right-handed individuals. The fact that this right- or left-sided preference is apparent so early on in human development suggests that genetically regulated mechanisms could be at play.

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To further probe how genetics might contribute to handedness, scientists at the Max Planck Institute (MPI) for Psycholinguistics turned to the UK Biobank, a large-scale biomedical database that contains genetic data from thousands of individuals in the UK. Their research is published in Nature Communications.

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Led by Dr. Clyde Francks, senior investigator in the language and genetics department at MPI, the scientists analyzed and compared exome data from 313,271 right-handed people and 38,043 left-handed people.

The collection of exons protein-coding DNA sequences in the genome is known as the exome.

A specific genetic variant was found to be much more common in left-handed people than right.

The beta-tubulin gene TUBB4B shows exome-wide significant association, with a rate of rare coding variants 2.7 times higher in left-handers than right-handers, the authors said.

TUBB genes encode proteins found in microtubules, which help to control the structure and movement of cells. Microtubules are prominent parts of the cytoskeleton the framework of protein filaments internal to cells that contributes to a wide range of processes including cellular growth, division, migration, shape and axis formation, axon outgrowth and intracellular transport, the researchers explained.

How microtubules affect variation in human handedness is not currently known. Previous research suggests a role in cellular chirality during brain development, which might impact the formation of the brains leftright axis.

Brain magnetic resonance imaging (MRI) data was only available for 13 of the UK Biobank TUBB4B variant carriers (left- and right-handers together), which is too small a sample for reliable association mapping with respect to brain structural or functional asymmetries, Francks and team said. Neither of the left-handed frameshift variant carriers had MRI data.

Some studies have identified TUBB genes as the underlying cause of incredibly rare neurological disorders. Intriguingly, mutations in TUBB2B can cause asymmetrical polymicrogyria (many and small folds) of the cerebral cortex, the researchers said. Mutations in TUBB3 can cause asymmetrical cortical dysplasia and unilateral hypohidrosis (reduced sweating on one side of the body, thought to be linked to disrupted function of the cortex, brain stem and spine). It may therefore be informative to collect brain MRI data from TUBB4B variant carriers in future studies, they add.

Reference: Schijven D, Soheili-Nezhad S, Fisher SE, Francks C. Exome-wide analysis implicates rare protein-altering variants in human handedness. Nat Comms. 2024;15(1):2632. doi: 10.1038/s41467-024-46277-w

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Is Left-Handedness Tied to Your Genetics? Possibly, New Study Suggests - Technology Networks