07 October 2013 Left and Right

Are you left-handed? If so, you’re in a special group making up around one in six of the population around the world. The bias towards right-handedness in our species is so unusual in the animal kingdom that humans have been dubbed the ‘Lopsided Ape’. But it’s not really clear what causes it. To solve the mystery, scientists are trying to unpick the genetic differences between us that might contribute to left- or right-handedness. So far they’ve discovered that genes involved in distinguishing the left and right sides of our bodies as we grow in the womb probably play a role in left and right handedness too. One of these is called NODAL, which (among its many other jobs) makes sure our heart grows on the left. Variations in another gene called PCSK6, which switches on NODAL, are strongly linked to left-handedness, hinting at the molecular machinery controlling this trait.

Written by Kat Arney

Genes for body symmetry may also control handedness

Lefties and righties can thank same DNA that puts hearts on left side for hand dominance

Left- or right-handedness may be determined by the genes that position people’s internal organs.

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About 10 percent of people prefer using their left hand. That ratio is found in every population in the world and scientists have long suspected that genetics controls hand preference. But finding the genes has been no simple task, says Chris McManus, a neuropsychologist at University College London who studies handedness but was not involved in the new research.

“There’s no single gene for the direction of handedness. That’s clear,” McManus says. Dozens of genes are probably involved, he says, which means that one person’s left-handedness might be caused by a variant in one gene, while another lefty might carry variants in an entirely different gene.

To find handedness genes, William Brandler, a geneticist at the University of Oxford, and colleagues  conducted a statistical sweep of DNA from 3,394 people. Statistical searches such as this are known as genome-wide association studies; scientists often do such studies to uncover genes that contribute to complex diseases or traits such as diabetes and height. The people in this study had taken tests involving moving pegs on a board. The difference in the amount of time they took with one hand versus the other reflected how strongly left- or right-handed they were.

A variant in a gene called PCSK6 was most tightly linked with strong hand preference, the researchers report in the Sept. 12 PLOS Genetics. The gene has been implicated in handedness before, including in a 2011 study by the same research group. PCSK6 is involved in the asymmetrical positioning of internal organs in organisms from snails to vertebrates.

Brandler, who happens to be a lefty, knew the gene wasn’t the only cause of hand preference, so he and his colleagues looked at other genetic variants that didn’t quite cross the threshold of statistical significance. Many of the genes the team uncovered had previously been shown in studies of mice to be necessary for correctly placing organs such as the heart and liver. Four of the genes when disrupted in mice can cause cilia-related diseases. Cilia are hairlike appendages on cells that act a bit like GPS units and direct many aspects of development of a wide range of species, including humans.

One of the cilia genes, GLI3, also helps build the corpus callosum, a bundle of nerves that connects the two hemispheres of the brain. Some studies have suggested that the structure is bigger in left-handers.

It’s still a mystery how these genes direct handedness, says Larissa Arning, a human geneticist at Ruhr University Bochum in Germany. In addition to genes that direct body plans, she says, the study suggests that many more yet-to-be-discovered genes probably play a role in handedness.

Brandler hopes the study will also help remove some of the stigma of being left-handed. Left-handedness isn’t a character flaw or a sign of being sinister, he says: “It’s an outcome of genetic variation.”

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