Genetic Linkage Study

Many of you have contributed to our genetic linkage study of over 400 families with at least 1 dyslexic child; this was the largest in the world so far. We have found a new site on chromosome 18 and are now trying to pin down the specific gene involved.

Even more excitingly we have also confirmed what had been suspected from earlier, smaller, studies that there is a gene on the short arm of chromosome 6 (6p21.3-23 for experts!) that contributes to dyslexic problems. We have now used more markers on this part of chromosome 6 to pin it down more precisely. We’ve been able to narrow our search to the 'promotor' region of the 'KIAA 0319' gene that is found there. This promotor seems to be down regulated, so the gene is less strongly expressed in dyslexics.

We've now shown that this gene, whose function was previously unknown, regulates the synthesis of 'signature' molecules on the surface of nerve cells. These help to control how they migrate to their final positions during development of the brain in utero. So it is likely that the underexpression of this gene is why some nerve cells in dyslexics fail to move to their correct positions during brain development, as has been found in dyslexic brains examined post mortem.

Also later in life, these cell signature molecules controlled by KIAA 0319 probably help neurones and antibodies to identify each other. This might explain why magnocellular neurones tend to fail to make effective connections in dyslexics, and why many dyslexics suffer from immune anomalies such as allergies and eczema.  But KIAA downregulation does not seem to affect general intelligence; so it is likely specifically to underlie the development of the special perceptual processes required for reading, possibly the development of magnocellular neurones. We’re at a very exciting juncture. Watch this space over the next few months!

In a large Finnish family a mutation in a gene on chromosome 15 (christened DYX1C1 because it was the first dyslexia gene to be discovered) is definitely associated with their dyslexic problems. However when we looked at the DNA of over 1000 individuals from our Oxford families we found that those who had this fairly common mutation actually had slightly better orthographic scores than those with the commonest variant. This suggests that the Finns have dyslexic problems because of a complex interaction of the C15 gene with another, as yet unidentified, more important one.