RESEARCH ADVANCE SPEEDS SEARCH FOR GENES
Instead of searching for disease causes gene by gene, researchers may now search entire chromosomes at once. Scientists at Case Western Reserve University School of Medicine, the Whitehead Institute for Biomedical Research, and Baylor College of Medicine discovered that by swapping one chromosome at a time in mice, they were able to detect the locations of genes involved in complex medical conditions more simply. Using this approach, the researchers found 17 locations for genes linked to diet-induced obesity, compared to past studies identifying only two to four genes. They also found eight locations for genes connected to cholesterol metabolism, while three previous studies had found only one to four locations. Once the gene location is found, researchers can look on the genetic maps created by Celera, Inc. to find the gene sequences. "The more genes we know about, the more potential candidates there are for drug targets to treat the disease," said one of the study's authors. The study is published in the April 16 issue of Science.
LONGEVITY GENE MAY BE LINKED TO BREAST CANCER PROGNOSIS
A gene known to promote longevity in animals has now been discovered to encode a tumor suppressor. A team of scientists from the University of Texas M.D. Anderson Cancer Center found the link between FOXO, linked to longevity in laboratory animals, and FOXO3, a tumor suppressor, while studying how normal cells turn cancerous. They then examined tumor cells from 131 breast cancer patients, finding FOXO3 in 113 of the samples. The protein was inactive in 83 samples, and active in the remaining 30. The scientists found a strong correlation between active FOXO3 and better patient survival. "This is a very good prognostic marker for breast cancer patient outcome," said one investigator. The study also found that FOXO3 is inactivated in many cancer patients by an enzyme called IKK, and determined that IKK is an oncoprotein. "This research has identified an important new tumor suppressor protein and a new oncogene that provides targets for cancer therapy," the study reports. The findings are reported in the April 16 issue of Cell.
GENE LINKED TO EVOLUTIONARY CHANGE IN FISH
In at least some fish, alterations in a single gene led to the loss of hind limbs, or fins. Researchers at the Stanford University School of Medicine made the discovery while studying a unique species of fish called the threespine stickleback. Pockets of these fish were isolated by geologic change at the end of the Ice Age, leading each separated population to evolve in response to local ecological conditions. Some of these populations lost their hind fins and associated spines. When the researchers bred these hind finless fish with their four-finned saltwater relatives, all the resulting fish had hind fins. This indicated that the fish needed only one copy of the saltwater genes to develop hind fins. The researchers linked this change from two-finned to four-finned to a gene that is the stickleback version of a gene in mice called Pitx1, that, when mutated, causes mice to have greatly reduced hind limbs. The results of this study were published in the April 15 issue of Nature.
PREDICTING CANCER PATIENT SURVIVAL WITH GENE EXPRESSION DATA
A procedure combining gene expression data and patients' clinical history is a powerful predictor of cancer patient survival. Scientists at Stanford have pioneered an approach that uses clinical data to identify a list of genes that correspond to a particular clinical factor - such as survival time, tumor stage or metastasis - together with statistical analysis to look for additional patterns in the data to identify clinically relevant subsets of genes. Using retrospective studies, they calculated the correlation of each gene in the microarray data with patient survival to generate a list of "significant" genes and then used those genes to identify tumor subtypes. The researchers believe this method will help identify new cancer subtypes, predict expected patient survival and help suggest the most appropriate course of treatment. The Public Library of Science Biology released the study on April 13.
CROHN'S DISEASE GENE IDENTIFIED
Researchers have isolated a gene that predisposes people to Crohn's disease, an inflammatory bowel disease. University of Toronto researchers used DNA samples from family groups, then employed positional cloning to first locate the chromosome containing the gene and then the gene itself. The gene codes for a protein that sits on the cell surface, regulating how substances enter and exit the cell. In the majority of Crohn's disease patients, this protein functions improperly, allowing toxins easier access to the cell. The ability to test for this protein malfunction will help physicians distinguish between Crohn's disease and ulcerative colitis, the other major form of inflammatory bowel disease known. "Isolating this gene is a critical step towards improved diagnosis of this disease and developing better therapies for Crohn's sufferers," said one researcher. A biotechnology firm called Ellipsis Biotherapeutics Corp. is currently investigating the mutant protein's effects on cell function with the eventual goal of developing treatments. The study was published online April 11 in Nature Genetics.
EDITORS: For more information about RESEARCH, contact George Stamatis at 216-368-3635 or [email protected]. For LONGEVITY, Nancy Jensen at 713-792-0655 or [email protected]. For GENE, Amy Adams at 650-723-3900 or [email protected]. For PREDICTING, Barbara Cohen at 415-624-1206 or [email protected]. For CROHN'S, Elaine Smith at 416-978-5949 or [email protected].
