Children's Hospital researchers identify genetic mutation that may predict organ...( Using a novel combination of cutting...)

Using a novel combination of cutting-edge technologies to scan the human genome, researchers at Children's Hospital of Pittsburgh of UPMC have identified a genetic mutation that identifies transplant recipients who experience rejection.

Known as a single nucleotide polymorphism (SNP), the genetic mutation validates the effectiveness of the system the researchers developed to search the human genome, according to principal investigator Rakesh Sindhi, MD, director of Pediatric Transplant Research in the Hillman Center for Pediatric Transplantation at Children's Hospital. They studied DNA samples from 80 children who received liver transplants and their parents.

"To identify mutations that mark a disease, from the millions of known mutations in the human genome, one needs to study hundreds, even thousands of patients with that disease. As a result, large-scale scanning of known mutations has not been applied to rarer diseases, such as those that affect children. However, by combining multiple layers of genetic information, with information from the cell types and processes affected by these genes, we can now study less common diseases using smaller numbers of subjects," Dr. Sindhi said. "Such mutations are likely to become the basis of a genomic fingerprint, which will allow us to predict who will experience rejection beforehand, and to personalize antirejection medication. The novel combination of techniques used in this study is a major methodological advance toward developing personalized diagnostics for transplant recipients, which will improve outcomes and quality of life."

Results of the study are published in the September issue of Gastroenterology, the official publication of the American Gastroenterological Association.

The approach used by Dr. Sindhi and colleagues involves powerful new tools known as microarrays. Over 500,000 known mutations spanning the entire genome are evaluated in one type of microarray. Th
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