Dyslexia may be one of the world's most common learning disorders, but it is no common task to establish the genetic factors that underlie this complex condition. As part of this ongoing quest, researchers at the Wellcome Trust Centre for Human Genetics (WTCHG), in collaboration with colleagues at the National Human Genome Research Institute (NHGRI), recently made a discovery that has opened a new window into dyslexia, as well as other common diseases caused by multiple genes.
At least one in 10 Americans has dyslexia, a brain-based disorder that can cause difficulty in reading and spelling. Both genetic and environmental factors are thought to contribute to the condition. Dyslexia tends to run in families, with the disorder affecting up to half of children born to parents with dyslexia.
Previous studies have found genetic variants associated with dyslexia in or near six genes, including several that have been implicated in brain development. But researchers have been unable to pinpoint exactly how any of these variants act to disrupt the brain's normal development or function. The research team now reports that it has identified a functional variant that can reduce production of a protein thought to play a key role in brain development
The research team focused on a region of human chromosome 6 near a gene called KIAA0319, which previous research indicated is important for proper development of areas of the brain involved in reading ability. Other studies also suggested that the gene may be involved in dyslexia, but no functional variants directly affecting the protein could be identified.
In this new study, the researchers looked at seven variants that did not lie within the KIAA0319 gene, which means the variants themselves did not code for a protein. Instead, such variants have the potential to serve influence the regulation of KIAA0319, indirectly affecting protein production by acting to turn the gene on or off. From this group of variants, the group zeroed in on one most strongly associated with dyslexia
Specifically, they found that the genetic variant creates a new transcriptional regulatory element where a regulatory protein called OCT-1 can bind to DNA. Previous work involving other genes had shown that when OCT-1 binds to DNA, it turns nearby genes off, preventing them from producing proteins.
Dr Paracchini of the WTCHG said: "This work shows for the first time the mechanism by which a common genetic variant (present in about 15% of the population) has an impact on cognitive function. These findings will help us to take a step forward in the understanding of dyslexia and might have diagnostic implications in a longer term. More in general the same approach we have described can be used to identify genetic variants that are functionally relevant to other common diseases such as cancer, diabetes or hypertension."
Dennis MY, Paracchini S, Scerri TS, Prokunina-Olsson L, Knight JC, et al. (2009) A Common Variant Associated with Dyslexia Reduces Expression of the KIAA0319 Gene. PLoS Genet 5(3): e1000436. doi:10.1371/journal.pgen.1000436
For more information on Dr Paracchini's dyslexia research, click here.