Category Archives: Genetic Medicine

To: HEALTH, MEDICAL AND NATIONAL EDITORS

MANHASSET, N.Y., March 9, 2012 /PRNewswire-USNewswire/ -- A collaborative group of investigators has joined together to identify five genetic variations associated with Crohn's disease (CD) and Jewish individuals of Eastern and Central European decent, who are also known as Ashkenazi Jews. These findings were published in the March issue of PLoS Genetics.

CD causes inflammation of the lining of the digestive tract and can be both painful and debilitating, and sometimes may lead to life-threatening complications. CD is two-to-four times more prevalent among individuals of Ashkenazi Jewish decent compared to non-Jewish Europeans. The study conducted at multiple institutions across the world, including the Feinstein Institute for Medical Research, was an important step toward understanding the genetic reasons for this higher prevalence.

"This large collaborative study made it possible to define more precisely the genetic contributions to Crohn's disease that are enriched in the Ashkenazi Jewish population, which has carried a higher risk for this disorder," said Peter K. Gregersen, head of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute. "The study identified genetic regions that hadn't been discovered before, and if additional studies of these regions are conducted there is a chance that biological pathways affecting susceptibility to Crohn's disease could be found and novel treatments could be developed."

About Crohn's Disease (CD)

CD causes inflammation of the lining of the digestive tract, which can lead to abdominal pain, severe diarrhea and malnutrition. CD can be both painful and debilitating, and sometimes may lead to life-threatening complications. There currently is no cure for CD, but available therapies can greatly reduce the signs and symptoms of CD.

About the Study

About The Feinstein Institute for Medical Research

SOURCE The Feinstein Institute for Medical Research

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Researchers Discover Five Genetic Variations Associated with Crohn's Disease in Ashkenazi Jews

ScienceDaily (Mar. 8, 2012) UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants -- meaning they needed lower doses of the drugs to affect 'mood' -- and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in The Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain's hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain's synapses," said Dr. Parada, an elected member of the National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. "Older mice lacking the protein responded as if they had been taking antidepressants all their lives," said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

Dr. Parada's laboratory has published a series of studies that link the Nf1 gene -- best known for mutations that cause tumors to grow around nerves -- to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body's immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease.

The current study's lead author is former graduate student Dr. Yun Li, now a postdoctoral researcher at the Massachusetts Institute of Technology. Other co-authors include Yanjiao Li, a research associate of developmental biology, Dr. Rene McKay, assistant professor of developmental biology, both of UT Southwestern, and Dr. Dieter Riethmacher of the University of Southampton in the United Kingdom.

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Genetic manipulation boosts growth of brain cells linked to learning, enhances effects of antidepressants

Public release date: 8-Mar-2012 [ | E-mail | Share ]

Contact: Emily Ng eng3@nshs.edu 516-562-2670 North Shore-Long Island Jewish (LIJ) Health System

MANHASSET, NY A collaborative group of investigators has joined together to identify five genetic variations associated with Crohn's disease (CD) and Jewish individuals of Eastern and Central European decent, who are also known as Ashkenazi Jews. These findings were published in the March issue of PLoS Genetics.

CD causes inflammation of the lining of the digestive tract and can be both painful and debilitating, and sometimes may lead to life-threatening complications. CD is two-to-four times more prevalent among individuals of Ashkenazi Jewish decent compared to non-Jewish Europeans. The study conducted at multiple institutions across the world, including the Feinstein Institute for Medical Research, was an important step toward understanding the genetic reasons for this higher prevalence.

"This large collaborative study made it possible to define more precisely the genetic contributions to Crohn's disease that are enriched in the Ashkenazi Jewish population, which has carried a higher risk for this disorder." said Peter K. Gregersen, head of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute. "The study identified genetic regions that hadn't been discovered before, and if additional studies of these regions are conducted there is a chance that biological pathways affecting susceptibility to Crohn's disease could be found and novel treatments could be developed."

About Crohn's Disease (CD)

Crohn's disease (CD) is an inflammatory bowel disease (IBD), which is one of the five most prevalent gastrointestinal disease burdens in the United States, with an overall health care cost of more than $1.7 billion. Each year in the United States, IBD accounts for more than 700,000 physician visits, 100,000 hospitalizations, and disability in 119,000 patients. CD is two-to-four times more prevalent among individuals of Ashkenazi Jewish decent compared to non-Jewish Europeans.

CD causes inflammation of the lining of the digestive tract, which can lead to abdominal pain, severe diarrhea and malnutrition. CD can be both painful and debilitating, and sometimes may lead to life-threatening complications. There currently is no cure for CD, but available therapies can greatly reduce the signs and symptoms of CD.

About the Study

Seventy-one genetic variants had already been identified in patients who had Crohn's disease (CD) and were of European decent. A collaborative group of investigators, including some from the Feinstein Institute for Medical Research, led by Inga Peter at Mt Sinai School of Medicine took a step further and conducted a genome-wide association study (GWAS) aimed at exploring genetic variation associated with CD in Jewish individuals of Eastern and Central European decent (Ashkenazi Jews). The study was conducted by combining raw genotype data across 10 Ashkenazi Jew cohorts consisting of 907 cases and 2,345 controls in the discovery stage followed up by a replication study in 971 cases and 2,124 controls. The study confirmed 12 of the known variants and identified five novel genetic varation regions not previously found. These five novel genetic regions were mapped to chromosomes 5q21.1, 2p15, 8q21.1, 10q26.3, and 11q12.1.

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Researchers discover 5 genetic variations associated with Crohn's disease in Ashkenazi Jews

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A study of kidney cancer patients finds the complexity of tumors may thwart simple attempts to personalize treatment.

A study of kidney cancer patients finds the complexity of tumors may thwart simple attempts to personalize treatment.

Cancer may be even more complicated than everybody already thought. And that's why a single tissue sample taken from a single tumor may not be the best way to figure out a course of treatment.

British researchers took multiple samples within kidney tumors (before and after drug treatment) and also got samples from tumors that had spread from the original cancers in four patients.

They performed all kinds of genetic tests, including detailed DNA sequencing, on the cancers and found wide variations in some key traits.

"We used every possible genomics technique available," senior author Charles Swanton told science blogger Ed Yong. "Even then we are only scratching the surface of the complexity within each cancer."

Even so, they found that some genetic variations that would be considered unfavorable for patients and others that would be good news for them were present in different parts of the same tumor.

Those results help explain why some treatments that seem like a good idea may not work. And they underscore the challenge in developing personalized tests and drugs for cancer therapy.

"It's a sobering finding," Andrew Futreal, a cancer geneticist and co-author of the study told The Wall Street Journal. The work was published in the latest New England Journal of Medicine.

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Detailed Genetic Tests Reveal Cancer's Complexity

Patients are holding out hope that someday soon, they hope physicians will be able to personalize medical treatment more precisely than theyve been able to in the past. For people with cancer, this might mean taking a quick biopsy, studying the genetic profile of a tumor and then tailoring interventions to target the cancer effectively, with as few side effects as possible.

But a study published in the New England Journal of Medicine on Wednesday underscores why the vision remains a challenge. Cancer researchers in England showed that individual kidney tumors and their metastases had different mutations in different locations and that those mutations, in turn, affect the biology of those tumors in varying ways in different locations.

A single tumor-biopsy-specimen reveals a minority of genetic aberrations that are present in an entire tumor, wrote Dr. Marco Gerlinger of the Cancer Research UK London Research Institute and co-authors.

For example, the scientists found that one region of a renal carcinoma could display gene expression signatures associated with a good prognosis, while signatures in another region of the same tumor could be associated with a poor prognosis.

The basic insight that a single cancer can contain a number of mutations isnt entirely new, but the teams genetic analysis helps demonstrate why it probably wont be possible to devise targeted, patient-specific treatment strategies by looking at minimally invasive biopsies collected from a single site, wrote Dr. Dan Longo of the National Institute on Aging in an editorial accompanying the study.

A new world has been anticipated in which patients will undergo a needle biopsy of a tumor in the outpatient clinic, and a little while later, an active treatment will be devised for each patient on the basis of the distinctive genetic characteristics of the tumor, he wrote. But a serious flaw in the imagined future of oncology is its underestimation of tumor heterogeneity.

The Los Angeles Times has reported on tumor genetics in the past. In April 2011, writer Amber Dance described efforts to catalog the mutations that cause cancer. Earlier that year, Thomas H. Maugh II explained how researchers sequenced the genomes of prostate cancers in seven different men.

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Personalized cancer treatment: Genetic differences abound in tumors

New Research Shows Personalized Treatment for Cancer Not So Simple

WebMD Health News

March 8, 2012 -- A small study that shows a surprising complexity of genetic changes within a single tumor has far-reaching implications for the march toward personalized cancer therapy, according to researchers.

A single biopsy from a tumor might not be sufficient to give a full picture of its genetic landscape, a team from the United Kingdom reports.

When the researchers examined 10 biopsies taken from a single kidney cancer tumor, they found "an extraordinary amount of diversity" in the genetic changes that had taken place in different parts of the tumor.

"There were more differences between biopsies from the same tumor at the genetic level than there were similarities," said researcher Charles Swanton, MD, PhD, from the Cancer Research UK, London Institute, and the University College London, United Kingdom.

The findings, published in the New England Journal of Medicine, were highlighted at a London news conference organized by Cancer Research UK, which funded the study.

The team also found differences in genetic changes between the primary tumor and places in the body where the cancer spread. Similar findings have been documented by other research groups.

But it is the extent of the genetic changes that is surprising, the researchers note.

The findings have far-reaching implications for the efforts currently being directed toward personalized cancer therapy, in which therapy is targeted at genetic changes identified in tumor tissue. Swanton cautioned that "if you take only one biopsy, you could be misled clinically."

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Genetic Makeup of Tumors More Complex Than Thought