William Brandler

Will

The Genetics of Dyslexia, Handedness and Cerebral Asymmetry

Developmental dyslexia is a difficulty with reading that cannot be accounted for by a lack of educational opportunity, general intelligence, or neurological damage. It is a highly heritable trait; the proportion of variation in the population that can be attributed to genetics is estimated at 40-70%.

The language centre of our brains is typically located in the left hemisphere. Functional brain imaging studies have shown that we use these same areas when we read. Since the left-hemisphere also controls the right side of our body and vice versa, most humans are also left hemisphere dominant for motor-control (handedness). This is reflected in the fact that 85-90% of individuals are right-handed and there are no known populations in the world in which left-handers are the majority. The heritability of hand preference (left / right) has been estimated at 25%.

It has been hypothesised that handedness emerged as a consequence of the evolution of language. Functional brain imaging studies have shown a weak correlation between handedness and cerebral dominance for language; with 96% of strong right-handers, compared to 73% of strong left-handers, showing left-hemisphere dominance for language. Also, there is suggestive evidence from structural brain imaging studies indicating that there may be atypical cerebral asymmetry in patients with neurodevelopmental disorders such as specific language impairment (SLI) or dyslexia. However, individuals with SLI and dyslexia are as likely to be right- or left-handed as the rest of the population.

Understanding the genetic basis of handedness can help define the relationships between handedness, language, cerebral asymmetry, and neurodevelopmental disorders. It may also offer us insights into human evolution, particularly with respect to language. Given the complex genetic nature of both handedness and dyslexia, very little is currently known about the specific variants and genes that contribute to these traits.

Therefore, my DPhil is concerned with utilising recent advances in genetic technologies in order to identify genetic variants associated with these traits, which will allow us to better understand their underlying biology.

I am supervised jointly by Prof. Anthony Monaco, Dr. Caleb Webber, and Dr. Andrew Morris. My DPhil is funded by the NDM Prize Studentship.

 

Publications

Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. (2013) Brandler WM, Morris AP, Evans DM, Scerri TS, Kemp JP, Timpson NJ, St Pourcain B, Smith GD, Ring SM, Stein J, Monaco AP, Talcott JB, Fisher SE, Webber C, Paracchini S. PLoS Genet. Sept 9. PMID: 24068947

 

PCSK6 is associated with handedness in individuals with dyslexia. (2010) Scerri TS, Brandler WM, Paracchini S, Morris AP, Ring SM, Talcott JB, Stein J, Monaco AP. Hum Mol Genet. Nov 9. PMID: 21051773 [Epub ahead of print]