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Genetic link to dyslexia

A gene variant involved in brain development may contribute to reading problems, including dyslexia

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4:15pm, October 3, 2008
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Unlike speaking, reading is a thoroughly unnatural act. That doesn’t mean that biology has no role in literacy. A gene involved in early brain development influences a range of reading problems, including dyslexia, a new study published online October 1 in the American Journal of Psychiatry suggests.

British children ages 7 to 9 who inherited a particular genetic sequence on chromosome 6 tended to perform poorly on tests of reading and spelling abilities, whether or not they had already been classified as dyslexic, say geneticist Silvia Paracchini of the University of Oxford in England and her colleagues. On average, carriers of the key genetic sequence scored as well on IQ tests as other kids did.

In an earlier report, the scientists found that the DNA sequence spans part of a gene called KIAA0319 and is linked to dyslexia in children in England and the United States. Paracchini’s group has also shown that the chromosome 6 sequence often accompanies a reduced ability of the KIAA0319 gene to direct the prenatal migration of brain cells to appropriate destinations.

Decreased protein production by KIAA0319 prompts subtle brain changes, beginning before birth, that contribute to reading problems, including dyslexia, the researchers propose.

“Our findings suggest that there is a wide degree of variability in reading ability across the population, and people with dyslexia are at one end of the spectrum,” Paracchini says.

It was important to search for an association of the chromosome 6 sequence with a range of reading difficulties, Paracchini says. Because the critical DNA sequence occurs in about 15 percent of both the general population and in children with dyslexia, studies that don’t account for youngsters who have reading problems that fall short of dyslexia may miss the relevant genetic link, in her view.

“This is a state-of-the-art, extremely well-done study, but we’re still left with major uncertainty about the nature of reading problems and dyslexia,” remarks YaleUniversity neuroscientist Sally Shaywitz. Such findings can’t be used to develop a genetic test for dyslexia or to make recommendations for reading instruction, she says. Genes and genetic sequences linked to reading difficulties, including the KIAA0319-related sequence, account for only a small amount of the differences in how children perform on reading tests, she explains.

Dyslexia characterizes people of at least average intelligence whose language problems include severe difficulties in sounding out written words, spelling and reading text fluently. This condition affects an estimated 4 percent to 15 percent of children and adults. No standard dyslexia measure or test exists.

Variants of at least six genes, including KIAA0319, have been reported to create a susceptibility to dyslexia. Attempts to replicate those results have yielded a mix of success and failure.

Paracchini and her coworkers studied more than 6,000 British children, born in 1991 and 1992 and participating in a long-term health investigation. For each child, the scientists conducted DNA analyses and examined scores on a battery of reading and spelling tests administered at ages 7 and 9.

For now, the scientists regard the chromosome 6 sequence as an indicator of susceptibility to reading problems in white children of European ancestry, who made up most of their sample.

Much remains unknown about how KIAA0319 may influence reading ability in different populations, Yale’s Shaywitz cautions. A 2007 investigation of 440 Australian families uncovered a link between the same gene sequence studied by Paracchini and especially proficient reading.

Paracchini’s team plans to probe for additional genetic sequences linked to reading problems in the same population of British children. The researchers will also explore possible environmental contributions to reading difficulties, including a lack of early exposure to books and disturbed relationships between parents and children.

Within the next decade, a major shift will occur in how scientists study reading and dyslexia, Shaywitz predicts. The emphasis will shift to probing the interactions of genetic, biological and environmental factors in individuals as they grow up and adopt any of a variety of strategies for decoding text, she says.

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