Durham, N.C. A research team led by scientists from the Duke University Medical Center has developed a way to simultaneously look at the effects of 125 mutations occurring on 14 different genes. They used zebrafish as a model to analyze the function of every known mutation in an inherited syndrome called BBS, Bardet-Biedl Syndrome.
Being able to analyze the functions and interactions of all mutations in a complex inherited disease could have implications for a broad range of disorders. The study found that, while mutations at one of at least 14 genes are responsible for the disorder, mutations elsewhere in the genome may modify the severity and diversity of the symptoms.
"The human genome project and new technologies can help us identify mutations in patients' genomes, but the challenge is how to interpret such variation and how to use it to improve the ability to predict what this means with respect to a patient's clinical presentation," said senior author Nicholas Katsanis, Ph.D., Jean and George Brumley Jr., M.D., Professor of Developmental Biology, Professor of Pediatrics and Cell Biology, and Director of the Duke Center for Human Disease Modeling. "Our work demonstrates that it is possible to develop functional bioassays using a vertebrate model that predicts whether a mutation has a role in a complex disease, like Bardet-Biedl syndrome, which we studied."
The study was published online during the week of May 24 in the Proceedings of the National Academy of Sciences.
BBS is an interesting disease to use as a study model because it involves a number of different traits that are highly variable among patients, said Katsanis, whose endowed professorship is in the Neonatal-Perinatal Research Institute at Duke. People with BBS may have retinopathy, obesity, mental retardation, more than the usual number of fingers or toes, and other distinct traits. BBS has become something of a workhorse for understanding variab
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Duke University Medical Center