U. of U. researchers find genetic clues to birth defects

Genomic technology » The study focused on a group of 30 youngsters, most of them age 2 to 8.
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University of Utah researchers studying a small group of people with different, rare forms of Down syndrome have produced a genetic map that may help shed new light on the causes of mental retardation and other birth defects.

Julie Korenberg, a professor of pediatric genetics at the U.'s Brain Institute, studied 30 people -- most of them ranging from 2 years to 8 years old -- who have missing or extra segments of chromosome 21. No two children had the same anomaly, she said.

Using state-of-the-art genomic technology, Korenberg was able to hone in on particular regions of genes that are likely responsible for eight different kinds of congenital malformations and diseases, some of which are not only found in people with Down syndrome, but also in the general population.

One gene, for example, plays a role in the formation of the heart and may offer a clue to the causes of congential heart disease. Yet others may be linked to leukemia and Alzheimer's disease.

Korenberg, who collaborated with researchers at Yale University and other institutions, published her findings today in the Proceedings of the National Academy of Sciences.

Sought out by parents of children with Down children, Korenberg began studying the children's genetic make-up in hopes of better explaining the cause of their syndrome.

One child, for instance, had a complete set of 46 chromosomes, but his chromosome 21 was too big.

"Frequently they (the parents) felt very lonely, to tell you the truth," said Korenberg, who is also the director of the Center for Integrated Neuroscience and Human Behavior at the U.'s School of Medicine. "They (the children) were rare and no one had seen anything like them."

Mapping these Down patients' genomes helped Korenberg winnow down sequences of genes and relate them to particular conditions and diseases. A number of the Down children with heart disease, for instance, had rare overlapping DNA duplications, allowing Korenberg to focus on a very small region that likely contains the gene or genes responsible for the condition.

"The fact we have these cases really delimits quite a number of genes," she said.

Korenberg said the next step is to further research the suspect genes in mouse models, as well as re-examine the original patients with Down syndrome to begin identifying genes that play a role in their brain structure and function.