Genetic variations that cause miscues in brain development may play an important role in dyslexia, according to new research presented last week at a meeting of the American Society of Human Genetics in Salt Lake City.
People with dyslexia have reading impairments despite normal intelligence. The problem affects between 5% and 17% of the population. In the last few years, geneticists have begun to point the finger at particular genes (ScienceNOW, 22 February). However, little is known about how these genes might contribute to the condition.
In one new study, a collaboration of 20 researchers led by Haiying Meng and Jeffrey Gruen of Yale University School of Medicine homed in on a region of chromosome 6 that has been implicated in previous dyslexia studies. Using DNA collected from 536 people with a dyslexic in their families, the researchers tracked 147 single-nucleotide polymorphisms (SNPs), places where the genetic code differs by one letter in different people. Searching for SNPs that tend to have one "spelling" in people with reading impairments and another spelling in normal readers, the researchers found that a disproportionate number of such SNPs showed up in a gene called DCDC2. They also found that about 17% of dyslexics in the study were missing a short stretch of DNA within DCDC2. Additional experiments with cadaver brains revealed high levels of DCDC2 expression in brain regions that are used during reading. And when the researchers used a technique called RNA interference to turn off DCDC2 in fetal rats, neurons didn't migrate to their proper positions in the cerebral cortex, the team reported at the meeting and online this week in Proceedings of the National Academy of Sciences. This suggests that certain variations of the DCDC2 gene may mess up the development of the neural circuits normally used for reading, says Gruen. People who inherit those variations probably compensate by using other, less efficient circuits for reading, he says.
Also at the meeting, and in a paper published 28 October in PLoS Genetics, Juha Kere of the Karolinska Institute in Stockholm, Sweden, and colleagues reported evidence linking a gene called ROBO1 to dyslexia. The fruit fly version of ROBO1 helps shape neural connections between the two sides of the brain during development. A third gene previously linked to dyslexia, KIAA0319, also may have a role in brain development, says Anthony Monaco at the Wellcome Trust Centre for Human Genetics in Oxford, U.K.
Before these studies no one really knew what in the brain was causing dyslexia, says Kere. Taken together, the new work strongly suggests that miscues during development are to blame, he says.
Related sites
Kere's
PLoS Genetics paper
Gruen's
site
Monaco's site
Dyslexia
information from NINDS
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