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Home | Pregnancy Timeline | News Alerts |News Archive Sep 17, 2013

 

Genes have an influence on whether we are left or right handed.






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Right or left-handedness genes identified

A genetic study has identified a biological process that influences whether we are right handed or left handed.

Scientists at the Universities of Oxford, St Andrews, Bristol and the Max Plank Institute in Nijmegen, the Netherlands, found correlations between handedness and a network of genes involved in establishing left-right asymmetry in developing embryos.

"The genes are involved in the biological process through which an early embryo moves on from being a round ball of cells and becomes a growing organism with an established left and right side," explains first author William Brandler, a PhD student in the MRC Functional Genomics Unit at Oxford University.


The research suggests that these genes may also help establish left-right differences in the brain, which in turn influences handedness.


They report their findings in the open-access journal PLOS Genetics.

Humans are the only species to show such a strong bias in handedness, with approximately 90% of people being right-handed. The cause of this bias remains largely a mystery.

Researchers, led by Dr Silvia Paracchini at the University of St Andrews, were interested in understanding which genes might have an influence on handedness, in order to gain an insight into its causes and evolution.

Carring out a genome-wide association study to identify any common gene variants that might correlate with which hand people prefer using, the most statistically significant variant was located in the gene PCSK6, which is involved in the early establishment of left and right in the growing embryo.

The researchers then made full use of knowledge from previous studies of what PCSK6 and similar genes do in mice to reveal more about the biological processes involved.


Disrupting the PCSK6 gene in mice causes 'left-right asymmetry' defects, such as abnormal positioning of organs in the body. A heart and stomach may develope on the right and the liver on the left, for example.

Scientists found that when disrupted in mice, gene variants known to cause left-right defects were more likely to affect relative 'hand skill' than expected by chance.


While the team identified a role for genes involved in establishing left from right in embryo development, William Brandler cautions that results do not completely explain the variation in handedness seen among humans.

He adds: "The development of handedness derives from a mixture of genes, environment, and cultural pressure to conform to right-handedness."

Abstract
Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10−9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development.


This work was supported by the University of St Andrews, the UK Medical Research Council, the Wellcome Trust, the Max Plank Society, and the EU 6th Framework Programme.

Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in the study.

The paper 'Common variants in left-right asymmetry genes and pathways are associated with relative hand skill' is to be published in the journal PLOS Genetics with an embargo of 22:00 UK time on Thursday 12 September 2013.

This paper details a genome-wide association study meta-analysis for a measure of relative hand skill in 728 individuals with dyslexia from three different cohorts. The results were replicated in a general population cohort of over 2,600 people who are unaffected with dyslexia (the longitudinal cohort ALSPAC).

The inclusion of three study groups of individuals with dyslexia is more accident than design. It just so happens that these studies in individuals with dyslexia included a test of relative hand skill. Being right or left-handed does not correlate with dyslexia. None of the genes in this study have any effect on the risk of developing dyslexia.

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. http://www.wellcome.ac.uk

Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK's top-ranked medical school.

From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.

Original press releas: http://www.ox.ac.uk/media/news_stories/2013/130913.html