Gene That Causes a Form of Deafness Discovered

Researchers at the University of Cincinnati and Cincinnati Children’s Hospital Medical Center have found a new genetic mutation responsible for deafness and hearing loss associated with Usher syndrome type 1.

These findings, published in the Sept. 30 advance online edition of the journal Nature Genetics, could help researchers develop new therapeutic targets for those at risk for this syndrome.

Partners in the study included the National Institute on Deafness and other Communication Disorders (NIDCD), Baylor College of Medicine and the University of Kentucky.

Usher syndrome is a genetic defect that causes deafness, night-blindness and a loss of peripheral vision through the progressive degeneration of the retina.

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Understanding how salamanders grow new limbs provides insights into the potential of human regenerative medicine

By studying a real lizard-like amphibian, which can regenerate missing limbs, the Salk researchers discovered that it isn’t enough to activate genes that kick start the regenerative process. In fact, one of the first steps is to halt the activity of so-called jumping genes.

In research published August 23 in Development, Growth & Differentiation, and July 27 in Developmental Biology, the researchers show that in the Mexican axolotl, jumping genes have to be shackled or they might move around in the genomes of cells in the tissue destined to become a new limb, and disrupt the process of regeneration.

They found that two proteins, piwi-like 1 (PL1) and piwi-like 2 (PL2), perform the job of quieting down jumping genes in this immature tadpole-like form of a salamander, known as an axolotl - a creature whose name means water monster and who can regenerate everything from parts of its brain to eyes, spinal cord, and tail.

"What our work suggests is that jumping genes would be an issue in any situation where you wanted to turn on regeneration," says the studies’ senior author, Tony Hunter, a professor in the Molecular and Cell Biology Laboratory and director of the Salk Institute Cancer Center.

The zebrafish is a major player in the study of vertebrate biology and human disease. Its transparent, externally fertilized eggs, short reproductive cycle and fast growth mean that its embryonic development can be studied closely while the animal is alive, and the fish is a useful model for studying gene behaviour and function.

Now, researchers led by Stephen Ekker, a molecular biologist at the Mayo Clinic in Rochester, Minnesota, have for the first time made custom changes to parts of the zebrafish (Danio rerio) genome, using artificial enzymes to cut portions of DNA out of targeted positions in a gene sequence, and replace them with synthetic DNA.

At any given moment, millions of cells are on the move in the human body, typically on their way to aid in immune response, make repairs, or provide some other benefit to the structures around them. When the migration process goes wrong, however, the results can include tumor formation and metastatic cancer. Little has been known about how cell migration actually works, but now, with the help of some tiny worms, researchers at the California Institute of Technology (Caltech) have gained new insight into this highly complex task.

The team’s findings are outlined this week online in the early edition of the Proceedings of the National Academy of Sciences (PNAS).

New gene-therapy approach could improve obesity treatment

Medical researchers at the University of Alberta have found a new way of using gene therapy to treat obesity. The treatment was successful, resulting in less weight gain, higher activity levels and decreased insulin resistance in lab models on a high-fat, high-sugar diet.

Faculty of Medicine & Dentistry researcher Jason Dyck, who works in the Department of Pediatrics and the Department of Pharmacology, published his findings this week in the peer-reviewed journal Nutrition and Diabetes. His team found a way to deliver the obesity treatment via DNA as opposed to a virus, which has had limited success in the past, especially over the long term. The results they demonstrated corroborated findings by other researchers who conducted short-term studies or used more risky methods of gene delivery.

“I think our findings may bring this treatment one step closer to clinical trials, as this approach appears to be much safer than conventional forms of gene therapy,” said Dyck.

The obesity treatment focused on increasing levels of adiponectin, a hormone secreted from fat cells. As a person gains weight and fat cells get larger, the body secretes less of this hormone. People who are thin secrete high levels of this hormone.

“This hormone seems to be protective against a number of diseases, including diabetes and cardiovascular disease, as well as weight gain,” says Dyck. “But as you gain weight, less adiponectin is secreted and you lose the beneficial effects associated with this hormone.”

Lab animal models fed a high-fat, high-sugar diet that were given this treatment gained less weight, burned more calories, were more active, used more oxygen, and were better protected against glucose intolerance and insulin resistance than those that were fed the same diet but didn’t get the anti-obesity treatment. Dyck hopes other research teams will move his work forward.

Researchers have long known that individual diseases are associated with genes in specific locations of the genome

Genetics researchers at the University of North Carolina at Chapel Hill now have shown definitively that a small number of places in the human genome are associated with a large number and variety of diseases. In particular, several diseases of aging are associated with a locus which is more famous for its role in preventing cancer.

For this analysis, researchers at UNC Lineberger Comprehensive Cancer Center catalogued results from several hundred human Genome-Wide Association Studies (GWAS) from the National Human Genome Research Institute. These results provided an unbiased means to determine if varied different diseases mapped to common ‘hotspot’ regions of the human genome. This analysis showed that two different genomic locations are associated with two major subcategories of human disease.

“Our team is interested in understanding genetic susceptibility to diseases associated with aging, including cancer,” said PhD student William Jeck, who was first author on the study, published in the journal Aging Cell.

First extensive analysis of Allen Human Brain Atlas published in Nature has implications for basic understanding of the human brain and for medicine

Scientists at the Allen Institute for Brain Science reported in the latest issue of the journal Nature that human brains share a consistent genetic blueprint and possess enormous biochemical complexity. The findings stem from the first deep and large-scale analysis of the vast data set publicly available in the Allen Human Brain Atlas.

The results of this study are based on extensive analysis of the Allen Human Brain Atlas, specifically the detailed all-genes, all-structures survey of genes at work throughout the human brain. This dataset profiles 400 to 500 distinct brain areas per hemisphere using microarray technology and comprises more than 100 million gene expression measurements covering three individual human brains to date. Among other findings, these data show that 84% of all genes are expressed somewhere in the human brain and in patterns that are substantially similar from one brain to the next.

"This study demonstrates the value of a global analysis of gene expression throughout the entire brain and has implications for understanding brain function, development, evolution and disease," said Ed Lein, Ph.D., Associate Investigator at the Allen Institute for Brain Science and co-lead author on the paper. "These results only scratch the surface of what can be learned from this immense data set. We look forward to seeing what others will discover."