Rare gene variant believed to play a role in understanding why people are left-hand dominant

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What do Lady Gaga, Barack Obama, Bill Gates, Paul McCartney and Justin Bieber have in common with Ronald Reagan, Jimi Hendrix, Judy Garland, Fidel Castro and David Bowie? They are all left-handed, a trait shared by roughly 10% of people.

But why are some people left-handed while most are righties? That is an area of active research, and a new study sheds light on a genetic component of left-handedness in some people. Researchers identified rare variants of a gene involved in controlling the shape of cells and found them to be 2.7 times more common in left-handed people.

While these genetic variants account for only a tiny fraction – perhaps 0.1% – of left-handedness, the researchers said the study shows that this gene, called TUBB4B, may play a role in the development of the brain asymmetry that underlies the determination of a dominant hand.

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In most people, the two halves, or hemispheres, of the brain have slightly different anatomies and are dominant for different functions.

“For example, most people have left-hemisphere dominance for language, and right-hemisphere dominance for tasks that require directing visual attention to a location in space,” said neurobiologist Clyde Francks of the Max Planck Institute for Psycholinguistics in the Netherlands, senior author of the study published on Tuesday in the journal Nature Communications.

“In most people, the left hemisphere also controls the dominant right hand. The relevant nerve fibers cross from left-to-right in the lower part of the brain. In left-handers, the right hemisphere is in control of the dominant hand. The question is: what causes the asymmetry of the brain to develop differently in left-handers?”

TUBB4B controls a protein that gets integrated into filaments called microtubules that provide internal structure for cells. The identification of rare mutations in this gene that are more common in left-handers suggests that microtubules are involved in setting up the brain’s normal asymmetries, Francks said.

The two cerebral hemispheres start to develop differently in the human embryo, though the mechanism has remained unclear.

“Rare genetic variants in just a handful of people can pinpoint genes that give clues to developmental mechanisms of brain asymmetry in everyone. TUBB4B could be a good example of this,” Francks added.

The findings were based on genetic data covering more than 350,000 middle-aged to older adults in Britain in a dataset called the UK Biobank. About 11% were left-handed.

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For most people, the determination of which hand is dominant may come down to chance.

“We think that most instances of left-handedness occur simply due to random variation during development of the embryonic brain, without specific genetic or environmental influences. For example, random fluctuations in the concentrations of certain molecules during key stages of brain formation,” Francks said.

Over the centuries, many cultures disparaged left-handedness and tried to force lefties to become right-handed. In English, the word “right” also means “correct” or “proper.” The word “sinister” derives from a Latin word meaning “on the left side.” And a “left-handed compliment” means an insult masquerading as praise.

The prevalence of left-handedness varies in different parts of the world, with lower rates in Africa, Asia and the Middle East compared to Europe and North America, Francks said.

“This likely reflects suppression of left-handedness in some cultures – making left-handed kids switch to right-handedness, which also used to happen in Europe and North America,” Francks added.

The new findings might have relevance in the field of psychiatry. While the overwhelming majority of left-handed people have neither of these conditions, people with schizophrenia are around twice as likely to be left-handed or ambidextrous and people with autism are around three times as likely, Francks said.

“Some of the genes that function in the developing brain during early life might be involved in both brain asymmetry and psychiatric traits. Our study found suggestive evidence of this, and we have also seen it in previous studies where we looked at more common genetic variants in the population,” Francks added.

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