Study: Rare gene could be source of left-handedness

[Dewsloth]

https://www.courthousenews.com/study-rar...andedness/

“This was really curiosity-driven research about a mystery in human biology: what is the genetic basis of the brain's left-right axis? We know that the two cerebral hemispheres already start to develop differently in the human embryo, but the mechanism is not known. Finding genes linked to asymmetries of the brain or behavior, like handedness, can give some clues,” said Clyde Francks, one of the authors of the study published Tuesday in Nature Communications, over email. 

Using data in a large biomedical database called UK Biobank, Francks and his colleagues trawled through the genetic data of 350,000 people looking for markers of left-handedness. They found a gene called TUBB4B — which gets integrated into microtubule proteins, which are filaments that acts as something akin to the internal skeleton of cells — which was 2.7 times more likely to show up in left-handed people than right-handed people.     

“It suggests that microtubules are involved in setting up the normal asymmetries of the brain, like left-hemisphere language dominance and hand control," Francks said. “In the embryonic brain, microtubules might help to create the left-right axis by giving some cells an asymmetrical twist at a certain stage.”

Francks and his colleagues also studied how genes that affect handedness, or which hand people use as the dominant one, are associated with aliments like schizophrenia, Parkinson’s disease, Alzheimer’s disease and autism.

"Exome-wide analysis implicates rare protein-altering variants in human handedness"
study is here:
https://www.nature.com/articles/s41467-024-46277-w

Handedness is a manifestation of brain hemispheric specialization. Left-handedness occurs at increased rates in neurodevelopmental disorders. Genome-wide association studies have identified common genetic effects on handedness or brain asymmetry, which mostly involve variants outside protein-coding regions and may affect gene expression. Implicated genes include several that encode tubulins (microtubule components) or microtubule-associated proteins. Here we examine whether left-handedness is also influenced by rare coding variants (frequencies ≤ 1%), using exome data from 38,043 left-handed and 313,271 right-handed individuals from the UK Biobank. 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 TUBB4B variants are mostly heterozygous missense changes, but include two frameshifts found only in left-handers. Other TUBB4B variants have been linked to sensorineural and/or ciliopathic disorders, but not the variants found here. Among genes previously implicated in autism or schizophrenia by exome screening, DSCAM and FOXP1 show evidence for rare coding variant association with left-handedness. The exome-wide heritability of left-handedness due to rare coding variants was 0.91%. This study reveals a role for rare, protein-altering variants in left-handedness, providing further evidence for the involvement of microtubules and disorder-relevant genes.