Rare Gene Variants Linked to Left-Handedness
A recent study has linked uncommon mutations in certain genes to the occurrence of left-handedness in humans. Understanding the implications of these genetic variations on other aspects of left-handers’ characteristics could provide insights into phenomena such as the genetic predisposition to neurodevelopmental disorders or the onset of neurodegenerative diseases.
Researchers from the Max Planck Institute for Psycholinguistics in the Netherlands analyzed genetic data from over 350,000 individuals. In their investigation, they identified potential correlations between brain-related disorders and rare genetic variations associated with left-handedness.
In nature, symmetrical orientations akin to mirrored hand reflections are quite common. Even at the molecular level, many entities exhibit consistent orientations known as chirality. For instance, the structural configuration of protein building blocks typically leans towards the left, while naturally occurring DNA in all living organisms twists in a right-handed manner.
Exploring Nature’s Preferences and the Prevalence of Left-Handedness
However, the reasons behind nature’s preferences for specific orientations are not always apparent. Despite possessing two equally capable hands and arms, there is a notable imbalance in handedness among individuals, with right-handers comprising the majority, while left-handers make up only around 10 percent of the population.
“This consistent bias remains prevalent across different continents and has remained stable throughout human history,” note geneticist Clyde Francks and his team in their published findings.
Left-handedness is more prevalent among individuals with certain neurodevelopmental disorders, and the connection between handedness and language has prompted extensive research. Increasingly, evidence suggests that our genes play a significant role in this relationship.
A study based on twins revealed that left-handedness is inherited in approximately one out of every four cases. Brain asymmetries responsible for hand dominance begin to develop early in life, with a baby’s hand preference observable even before birth.
Researchers are making headway in identifying the genetic factors underlying the specialization of our left hand in tasks that our non-dominant hand finds challenging, such as writing.
In 2019, an analysis of 400,000 individual records identified the initial four genetic regions associated with left-handedness. Subsequently, a genome-wide association study involving over 1.7 million individuals in 2020 pinpointed 41 gene variants influencing left-handedness.
Genetic Insights into Left-Handedness
“Implicated genes include several encoding tubulins (components of microtubules) or microtubule-associated proteins,” the researchers note. “In this study, we explore whether rare coding variants also impact left-handedness.”
The researchers examined genetic data from more than 350,000 individuals in the UK Biobank to assess the influence of rare gene variants on left-handedness. Their analysis encompassed 38,043 left-handed individuals and 313,271 right-handed individuals.
They identified specific genes linked to left-handedness and calculated the collective impact of these rare genetic alterations on left-handedness. At the population level, they determined that the heritability of left-handedness associated with these rare coding variants was approximately 1 percent.
Franks and his team discovered that left-handed individuals are 2.7 times more likely to carry rare coding variants in the TUBB4B gene, which codes for tubulins involved in microtubule assembly.
Microtubules constitute a component of the cytoskeleton, which is integral to cell structure and plays a crucial role in neuronal development, migration, and plasticity.
“The mechanism by which microtubules influence individual variability in human handedness remains unclear,” state the authors, “but it’s been proposed that they may contribute to cellular chirality during early brain development, thereby influencing the intrinsic formation of the brain’s left-right axis.”
Genetic Links to Left-Handedness
Despite the lack of correlation between left-handedness and any of the nine genes associated with neurodegenerative conditions in extensive exome studies, individuals with alterations in two genes linked to autism, namely DSCAM and FOXP1, may demonstrate notably increased likelihoods of being left-handed.
While the majority of left-handed individuals do not have autism, the authors suggest that the elevated incidence of left-handedness may stem from rare genetic alterations. When DSCAM or FOXP1 mutations contribute to autism, it’s plausible that changes in the development of the brain’s left-right axis play a role.
“This study highlights the involvement of rare, protein-altering variants in left-handedness, offering additional evidence for the significance of microtubules and genes relevant to disorders,” conclude the authors.
Francks and his team anticipate that larger-scale studies employing rare variant association mapping will likely identify additional genes associated with left-handedness.
Read the original article on: Science Alert
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