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Utah Researchers Confirm Chromosome may Harbor Autism Gene

Published: Wednesday, January 18, 2006
Last Updated: Wednesday, January 18, 2006
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Researchers have ruled out one gene that appeared to be a good candidate for being linked to autism.

Using technology that allows DNA from thousands of genes to be collected and surveyed on a 3 x 1½-inch chip, University of Utah medical researchers have confirmed that a region on a single chromosome probably harbors a gene that causes autism.

The researchers at the U School of Medicine made the finding by tracing variations in the DNA of an extended Utah family that has a high occurrence of the disorder and whose members are descended from one couple.

As part of the study, the researchers also ruled out one gene that appeared to be a good candidate for being linked to autism. They're now looking at other genes for a connection to the disorder.

Published in Human Heredity online, the study is part of the Utah Autism Research Project. The researchers are interested in finding more families with a history of autism to join the study.

The just-published research confirms Finnish studies of families that linked autism to the same region on chromosome 3, according to principal author Hilary Coon, Ph.D., research associate professor of psychiatry.

In fact, the results of the U of U research were surprisingly similar to the Finnish studies, Coon said.

"It was remarkable to confirm the Finnish studies," she said. "Our results were so close to their evidence, we thought it was important."

The study involved 31 members of a family of Northern European ancestry, seven of whom have autism or an autism-related disorder. The family members are part of the Utah Population Database.

The researchers used a gene chip similar to a microarray to search for genetic markers of autism.

They used a coated glass chip from Affymetrix, Inc. This chip has 10,000 short segments of DNA with known gene sequence variations, called single nucleotide polymorphisms, attached to 3/8 by 3/8-inch area.

The DNA strands of the family members were broken up and then bonded to the DNA on the chip, allowing researchers to compare the variations in the SNPs of the different DNA on an extremely fine scale.

The chance of the same variants of SNPs in a particular region on a chromosome being passed through several generations from a founding couple to multiple affected family members is slight.

When such identical blocks of SNPs are found, the chromosomal region often is a good candidate for being linked to a disease.

Other studies, including the Finnish ones, have found a high degree of evidence linking chromosome 3 to autism, so Coon and the other U researchers began their search on that chromosome.

The first region of the chromosome they looked at contained 106 SNPs, 70 of which strongly indicated a gene in that region being linked to autism.

One gene, FXR1, appeared to be a likely candidate for a link to autism. FXR1 is similar to the X-chromosome Fragile X gene, FMR1.

Mutations in FMR1 cause Fragile X Syndrome, an inherited condition that can cause mental impairments ranging from learning disabilities to severe cognitive problems.

Fragile X syndrome has been shown to overlap with autism, and because FXR1 is similar to the gene that causes the syndrome, U researchers suspected FXR1 might be linked to autism. But after analyzing the entire coding sequence of FXR1, the researchers found no alterations in the gene likely to contribute to autism.

Based on statistical evidence, they're now looking at other genes. But evidence that a gene on a particular region of chromosome 3 is linked to the disorder doesn't preclude other genes from being a cause of autism, according to Coon.

"We're just looking for the needle in the haystack," Coon said.

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