Daily Archives: February 24, 2017

Researchers provide further evidence of how gene mutations in a certain brain region might fuel behaviors associated with obsessive-compulsive disorder. The findings could pave the way for new treatments for the condition.

Obsessive-compulsive disorder is a condition characterized by uncontrollable thoughts, obsessions, and compulsions.

Obsessions include repetitive thoughts or mental images that trigger anxiety, while compulsions refer to the urge to repeat certain behaviors in response to obsessions. Common examples of compulsions include excessive hand-washing, arranging items in a particular way, and compulsive counting.

OCD is estimated to affect around 1 percent of adults in the United States. Of these adults, 50 percent have severe OCD, which can significantly interfere with daily life.

While the precise causes of OCD are unclear, previous studies have suggested that the disorder may be caused by specific gene mutations.

In the new study, researchers from Northwestern University in Chicago, IL, have pinpointed gene mutations in the corticostriatal region of the brain that led to OCD-like behaviors in mice.

Lead author Anis Contractor, associate professor of physiology at Feinberg School of Medicine, and colleagues recently reported their findings in the journal Cell Reports.

In humans and mice, the corticostriatal brain region is responsible for regulating repetitive behavior. "People with OCD are known to have abnormalities in function of corticostriatal circuits," notes Contractor.

By analyzing this brain region in mice, Contractor and colleagues identified a number of synaptic receptors - called kainate receptors (KARs) - that play a key role in the development of the corticostriatal region.

The researchers then set out to investigate whether disrupting KAR genes in mice - thereby eliminating KARs - might induce repetitive behavior in the rodents. They found this was the case.

Mice whose KAR genes were erased displayed a number of OCD-like behaviors, such as over-grooming and repeatedly digging in their bedding.

The team says these findings provide further evidence that KAR genes play a role in OCD in humans, and a possible biological mechanism.

"A number of studies have found mutations in the kainate receptor genes that are associated with OCD or other neuropsychiatric and neurodevelopmental disorders in humans.

I believe our study, which found that a mouse with targeted mutations in these genes exhibited OCD-like behaviors, helps support the current genetic studies on neuropsychiatric and neurodevelopmental disorders in humans."

Anis Contractor

The team suggests that in the future, KAR genes could be a target for the development of new drugs to treat OCD.

Learn how exposure therapy might help treat people with OCD.

See more here:
Gene mutations in brain linked to OCD-like behavior - Medical News ... - Medical News Today

A newly discovered type of genetic mutation that occurs frequently in cancer cells may provide clues about the diseases origins and offer new therapeutic targets, according to new research from Weill Cornell Medicine and the New York Genome Center.

Using next-generation sequencing technology, scientists have previously traced cancers roots to mutations that disrupt the sequence of proteins. As a result, the cell either creates hyperactive or dysfunctional versions of proteins, or fails to produce them at all, leading to cancer. Now, a study published Jan. 12 in Cell illuminates a possible new type of driver of the disease: small (one-50 letter) insertions or deletions of DNA sequence, also called indels, in regions of the genome that do not code for protein.

Dr. Marcin Imielinski Photo credit: John Abbott

Those non-coding regions are still important because they contain sequences that affect how genes are regulated, which is critical for normal cell development, said lead author Dr. Marcin Imielinski, an assistant professor of pathology and laboratory medicine at Weill Cornell Medicine and a core member at the New York Genome Center. We already know they are biologically important. The question is whether they can impact cancer development.

In the study,Dr.Imielinski and colleagues from the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute analyzed sequencing data from several publicly available databases of tumor samples, focusing on the 98 percent of the genome that does not code for protein. They initially looked at lung adenocarcinoma, the most common type of lung cancer, and found that the most frequent indel-mutated regions in their genomes landed in genes encoding surfactant proteins. Though these genes are essential for healthy lung function, they had not previously been associated with lung cancer. However, they are highly and specifically expressed by the cell type that gives rise to lung adenocarcinoma.

The researchers then looked at the genomes of 12 other cancer types and found similar patterns in liver, stomach and thyroid tumors. In each cancer, noncoding indels clustered in genes that are critical to organ function, but had not been associated with the cancer, said Dr. Imielinski, who is also an assistant professor of computational genomics in theHRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicineand a member of theSandra and Edward Meyer Cancer Centerat Weill Cornell Medicine.

This image shows genetic mutations (blue) in the context of their surrounding DNA sequence, highlighting a sequence motif (red) that Dr. Imielinski discovered.

Most strikingly, these non-coding indels are very common, occurring in 20-50 percent of the associated cancers. They occur as frequently as the most famous cancer-causing mutations, said Dr. Imielinski, who is a paid consultant for the company 10X Genomics, which sells devices and technology to analyze genetic information. Any gene or any sequence that mutated at this frequency has been shown to play a causal role in cancer. That would be an exciting outcome, if we can prove it.

Even if these mutations are not shown to cause cancer, they can be used in the future to improve cancer diagnosis and treatment. These mutations can be biomarkers that help us to diagnose a cancer early, or they could be used to pinpoint a primary cancer when there are metastases and we cant find the original cancer, Dr. Imielinski said. There are a lot of potential clinical implications from these findings.

Original post:
New Type of Genetic Mutation Identified in Cancer - Cornell Chronicle

Solast week the feds may have dashedUC Berkeleys billion-dollar dreams when it decided not to give the universitypatent rights over CRISPR-Cas9, a revolutionary gene-editing technology.

The Feb. 15ruling from the U.S. Patent and Trademark Office let Berkeleys rivaltheBroad Institutejointly owned by Harvard and MITkeep itsexisting patents issued in 2014.UC Berkeleyhas yet to say whether or not it will appeal.

Berkeley was seeking to have some of those patents repealedbecause the university says they conflict with its pending patent application for CRISPR.

The judges reasoned that Berkeleys patent request doesnt affect Broads existing patents because the two are based on different gene editing techniques.

Berkeleys patent request is for editing genes in bacteria, whereas Broads existing patents are for editing genes in eukaryotic cells, i.e. cells found in plants and animals, including humans.

But Berkeleyargues that its research toolcan easily be extended to use in non-bacterial cells.

That distinction is key since potentially lucrative applications of gene editing in medicine and health will involve eukaryotic cells found in humans.

UC Berkeley biologist Jennifer Doudna, who is credited with co-inventingCRISPR-Cas9 now has two options:

1) Appeal to the U.S. Court of Appeals for the Federal Circuit 2) Go back to the U.S. Patent and Trademark Office

If Berkeley appeals, the court could overrule the patent office decision in favor of Berkeley.

If Berkeley loses, it could go backto the patent office, where itcould be required to narrow itsclaims, i.e., specifying that its technique is only intended to be used in bacteria.

Or it could get a broad patentthat still doesnt specifyhow to use CRISPRin eukaryotic cells. But according to Jacob Sherkow, a law professor at New York Law School, that could lead to future legal challenges.

Its not going to be that strong because anyone who wants to challenge it later can say, that patent doesnt disclose how to use the tool in eukaryotic cells,' says Sherkow.

And the money is in altering those specific cells.

So whats next? Only Berkeley knows; the university has said it will carefully consider all options.

Science journalists are abuzz about what this means for biotech. Heres a sampling of what theyre saying:

1.Berkeley + Broad = VirtualMonopoly on CRISPR-Cas9 (Gizmodo)

Why does this matter? While academic researchers can still use CRISPR for free, companies hoping to harness the gene editing tool to fight disease, solve agricultural problems, or for myriad other potential applications, may have to pay not one, but both institutions, a hefty fee. Its a decision that has caused some to wonder whether the rights to such revolutionary technology dont really belong to a third party: the people.

2. Could the Case Encourage Scientiststo Be Less Honest?(STAT)

The patent judges concluded that the inventors themselves were uncertain about making CRISPR work in human cells.

That could send a terrible message to scientists, said Dr. Robert Cook-Deegan of Arizona State University, an expert on legal and ethical issues surrounding biotechnology. I hope this does not become the poster child that patent offices use to coach scientists not to be honest about uncertainties about their discoveries, he said. The fact that Doudnas quotes were used by the judges mainly tells me Doudna was being honest. I hope scientists will continue to be honest and not succumb to being told they cant say things that might undermine a broad patenting strategy.

3. Fogettaboutit, Companies Can SidestepBerkeleyand Broad(Nature)

Researchers in academia and industry have been pushing CRISPR gene editing beyond the scope of the Broad and Berkeley patents.

Both patent families cover the use of CRISPRCas9, which relies on the Cas9 enzyme to cut DNA. But there are alternatives to Cas9 that provide other functions, and a way to sidestep the BerkeleyBroad patent fight.

One attractive alternative is Cpf1, an enzyme that may be simpler to use and more accurate than Cas9 in some cases. The Broad has already filed patents on applications of Cpf1 in gene editing, and has licensed them to biotech company Editas Medicine in Cambridge, Massachusetts.

Remember, my friends, if UC Berkeley appeals, this whole process could last through 2020. Or longer.

Lindsey Hoshaw is an interactive producer for KQED Science. Before joining KQED, Lindsey was a science correspondent for The New York Times, The Boston Globe, Forbes and Scientific American. On Twitter @lindseyhoshaw

Excerpt from:
CRISPR Patent Ruling: 3 Different Takes - KQED