Daily Archives: January 18, 2014

Jan. 16, 2014 Gene therapies developed by University of Pennsylvania School of Veterinary Medicine researchers have worked to correct different forms of blindness. While effective, the downside to these approaches to vision rescue is that each disease requires its own form of gene therapy to correct the particular genetic mutation involved, a time consuming and complex process.

Hoping to develop a treatment that works more broadly across diseases, a Penn Vet team used canine disease models to closely examine how retinal gene activity varied during the progression of three different forms of inherited vision disease. Their results turned up an unexpected commonality: Early on in each of the diseases, genes involved in the same specific pathway of cell death appeared to be activated. These findings point to possible interventions that could curb vision loss across a variety of inherited retinal diseases.

The work, published in PLOS ONE, was conducted by Sem Genini, a senior research investigator; William A. Beltran, assistant professor of ophthalmology; and Gustavo D. Aguirre, professor of medical genetics and ophthalmology, all of Penn Vet's Department of Clinical Studies, Philadelphia.

The team examined three forms of retinal degenerative diseases, rod cone dysplasia 1 being the most severe, or earliest onset, followed by X-linked progressive retinal atrophy 2 and then early retinal degeneration. All of these diseases involve the death of photoreceptor cells and each is caused by a distinct genetic mutation. But what scientists did not know is how the mutations trigger a molecular signaling pathway that leads to the death of photoreceptor cells.

"What we have in mind is to be able to address multiple forms of disease with one treatment," Beltran said. "We wanted to get a better understanding of whether there are any common cell death or cell survival pathways that could be targeted in some of these diseases."

The researchers looked at the activity of 112 genes in diseased retinas and compared it to gene activity in normal retinas. They assessed gene activity at time points known to correspond with key phases of disease: the "induction phase," the time before the peak level of photoreceptor cell death; the "execution phase," when the highest rates of photoreceptor cell death occur; and the "chronic phase," during which photoreceptor cell death continues at somewhat reduced levels.

During the execution and chronic phases of disease, the researchers identified a number of genes involved in programmed cell death, or apoptosis, that had noticeably different patterns of expression between the diseased and normal dogs.

Of note, several proteins involved in the tumor necrosis factor, or TNF, pathway increased in activity during the induction and execution phases. This pathway is implicated in many diseases, from diabetes to cancer to rheumatoid arthritis.

"This is quite a new result," Genini said. "It was not expected to have the TNF pathway upregulated."

"We assumed," Aguirre said, "the diseases would be different from one another and that cells would commit suicide by their own specific pathway and that perhaps quite late they would have a common final pathway. But what this shows is that there is an early trigger that is quite similar among all three diseases."

Read more from the original source:
Same cell death pathway involved in three forms of blindness, study finds

A new supercomputer can sequence 20,000 genomes in a year for $1,000 a piece.

On Tuesday, Illumina, a global company that specializes in genomic analysis, announced the sale of a new genetic sequencing machine, that is faster and more affordable than existing technology.

"The new sequencer packs high-throughput performance into an affordable desktop form factor, enabling researchers to perform the most popular sequencing applications in less than a day,"said Jay Flatley, CEO of Illumina in a press release.

[READ: Researchers Link Aging Gene to Blood Cancer]

The new technology can sequence a whole human genome in a single run. And the sequencing data can be fed through open source or commercial programs or transferred, analyzed and stored in a secure space, the release noted.

The new machine can sequence 20,000 genomes in a year for $1,000 a piece, says HPC Wire. It can process 16 complete human genomes in three days. The "$1000 genome" is a long-sought marker of advancement that industry has seen as "a tipping point in the pace of genetic discovery" says Aaron Kroll at BioITWorld.

Dr. Gianrico Farrugia, director for the Center for Individualized Medicine at the Mayo Clinic, says that the new machinery's reduced cost and its ability to do large-scale processing will affect the reliability of doctor's results. When testing a person's genome having a larger data set to compare anomalies with will allow doctors to rule-out false positives that can sometimes occur when the pool of comparison data is too small. Doctors need to be certain that "what we call as abnormal is in fact abnormal," he says.

"So, being able to do this significantly larger scale sequencing at a lower cost allows you to collect information that you can apply to your individual patient, because you have more information," he adds.

Farrugia says he knew that the technology was being tested, but didn't know when it would be available. He's excited to try out the new machines and apply them to patient care. The first full human genome sequence was published in April 2003 for $3 billion, according to HPC Wire.

[STUDY: Same Genes May Cause Alcohol Abuse, Eating Disorders]

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New Gene Machine Could Mean More Accurate Diagnosis