Pediatrics researchers at the Children's Hospital of Philadelphia and McGill University in Montreal have identified a gene variant that raises a child's risk for type 1 diabetes, formerly called juvenile diabetes. As investigators continue to pinpoint genes contributing to diabetes, they have their eyes on providing a scientific basis for designing better treatments and preventive measures for the disease.
The research adds a new gene and new knowledge to the four genes previously discovered for type 1 diabetes, in which the immune system destroys insulin-producing beta cells in the pancreas and makes patients dependent on frequent insulin injections to keep the body's blood sugar under control. As the project continues, the study team expects to identify additional genes (perhaps as many as 15 or 20) thought to interact with each other in the disease.
The study appeared July 15 in an advance online letter in the journal Nature.
"The genotyping technology we now have available has revolutionized the way we can ask and answer research questions," said the study's lead author, Hakon Hakonarson, M.D., Ph.D., the director of the Center for Applied Genomics at The Children's Hospital of Philadelphia.
"Unlike the previous technology, which was quite limited and dealt largely with relatively rare gene variants, we can now detect common genetic variants that are important in large numbers of individuals, and begin to understand how multiple genes interact in complex diseases such as diabetes."
In the discovery phase of the study, the investigators examined the genomes of 1,046 children with type 1 diabetes. These DNA samples came from patients and families followed in pediatric diabetes clinics in Philadelphia and four Canadian cities.
Specifically, the researchers compared the genomes of 563 patients with type 1 diabetes with those of 1,146 matched control subjects. Those results were combined with those obtained from an independent analysis of 483 family trios, in which the genomes of a child with the disease and both parents were examined.
The researchers confirmed the four previously identified locations for genes contributing to type 1 diabetes, but also uncovered a new type 1 diabetes locus on chromosome 16, occupied by a gene called KIAA0350. The team then replicated this discovery in yet another independent cohort of 1,333 children with the disease from the Type 1 Diabetes Genetics Consortium, which includes children of European descent in Europe, North America and Australia, as well as in 390 additional type 1 diabetes family trios from Canada.
The current research used a technique called genome-wide association, in which highly automated analytic equipment rapidly scans each patient's DNA for more than half a million genetic markers. It was performed at the Center for Applied Genomics at Children's Hospital. The Center's tools spell out a patient's genotype -- the specific pattern of variations among an individual's 30,000 genes. Established in the summer of 2006, the center is taking on one of the largest genotyping projects in the world, and is the largest one dedicated to genetic analysis of childhood diseases.
Financial support for the study came from Genome Canada through the Ontario Genomics Institute, the Juvenile Diabetes Research Foundation and The Children's Hospital of Philadelphia. Hakonarson's and Polychronakos' co- authors were affiliated with the University of Pennsylvania School of Medicine, the University of Manitoba, the Children's Hospital of Eastern Ontario, the University of Ottawa, and Markham-Stoufville Hospital of Markham, Ontario.