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Category Archives: Genetic Medicine
Four new studies this week take on the genetics of autism, finding further evidence that older fathers are at increased risk of having an autistic child and suggesting that, overall, the genetic roots of the condition are incredibly complex.
Three of the studies, which were published in Nature, looked at new, or de novo, genetic mutations, which are not inherited but occur spontaneously around conception, in autistic children without any affected siblings.The researchers compared these children to each other and in some cases, also to their parents, and found changes in six candidate genes, three of which hadnt previously been linked to autism.
The basic finding is that new mutations present in sex cells carry substantial risk for autism, says Dr. Matthew State, a professor of psychiatry at Yale, who led one of the studies.
States study found that 15% of autism cases in families with no other autistic children were linked to de novo mutations in either the sperm or the egg that joined during conception. The three studies overall confirmed prior research suggesting that older fathers sperm is more likely to carry these mutations. In one study, researchers at the University of Washington in Seattle found that the mutations were four times more likely to occur in the fathers than in the mothers and the risk for men began increasing at age 35.
That may be because the older men are, the more times their sperm-creating cells have copied themselves, and each time a cell is copied, there is a chance that a mutation will occur. Previous studies have found that men over 50 have double the risk of having an autistic child, compared with those under 30, and the odds are four times greater for those over 55.
(MORE: Researcher Simon Baron-Cohen: Autisms Lone Wolf)
In another of the Nature studies, Harvard researchers found that de novo mutations were slightly higher among autistic people than those in the general population. The findings may help explain the recent rise in autism a government study last week put the rate of autism at 1 in 88 U.S. children which has occurred too quickly to be explained by the spread of hereditary genes. While more than half of the risk of autism is believed to be inherited studies find, for example, that 60% to 90% of identical twins are both autistic, sometimes to differing degrees in at least 70% of cases of autism, a known underlying genetic cause cant be identified.
The researchers focused on mutations that were most likely to interfere with gene function not those that most people acquire but are harmless thereby narrowing their search to those rare mutations that may occur only in autistic people. Then, they narrowed things further by looking at genes that had at least two such mutations. The odds that two or more mutations that cause serious problems with protein-making in the same gene also occur by chance in autism are infinitesimal.
These are like lightning strikes in the genome, State says, noting that the technique researchers used to find them should allow them to home in on genes that are genuinely important in the disorder. We are [now] able to determine what the threshold should be for calling something an autism gene.
Now we have real path forward, State says, explaining that as you start to accumulate these individual genes that you know are related, that opens the door to understanding the biology. Once you know the gene, you can examine the protein it makes. Then, even in people who dont have the damaged gene, adding that protein may help because a deficit in that protein might result in their autism via a different pathway.
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Autism Studies Confirm Genetic Complexity and Risk for Older Fathers
New York geneticist Robert Marion, MD, envisions a future where whole-genome sequencing will be used to help prevent many medical conditions from developing.
Geneticists say this new era of medicine could occur within a decade, thanks to the complicated procedure being tested in a growing number of research settings across the country.
In whole-genome sequencing, geneticists use a patients blood sample or other source of genetic material to examine the 20,000 to 25,000 genes that make up an individuals genome. By comparison, standard genetic testing used widely by health professionals today examines only individual genes, geneticists say. As a result, physicians often must order multiple tests to get needed genetic information.
Whole-genome sequencing will enable specialists to identify variations in a persons genetic code that increase his or her genetic risk of developing a spectrum of conditions, including Alzheimers disease, cancer, diabetes and schizophrenia. The procedure also will reveal the cause of undiagnosed symptoms, an individuals propensity for becoming dependant on nicotine, and the likely effect of medication on conditions such as asthma and cardiovascular disease.
Some geneticists estimate that within five years, as the procedure becomes more affordable, primary care physicians will begin sifting through patients whole-genome sequence results and creating preventive care plans for conditions the individual is at risk of developing. In 10 years, such sequencing could become a routine part of medical care performed on newborn babies and older patients.
An estimated 20,000 to 25,000 genes make up a persons genome.
Medicine will go from a field where we are reactive to one in which we can prevent symptoms and signs from ever occurring. Thats really a game-changer in medicine, said Dr. Marion, chief of the division of genetics and child development in the Dept. of Pediatrics at the Childrens Hospital at Montefiore and the Albert Einstein College of Medicine in New York.
But these experts admit there are uncertainties and ethical concerns about whole-genome sequencing that need to be resolved before it becomes a standard procedure used by physicians for patients. Among the chief worries is what to do with the large number of variants in genes associated with human disease that can show up in a patients sequencing.
The genome is so complex and some of our understanding of various mutations is so shaky that its hard to tell which information is meaningful and which isnt, said Robert C. Green, MD, MPH, associate professor of medicine in the Division of Genetics at Brigham and Womens Hospital and Harvard Medical School in Boston.
There are no guidelines on which findings from whole-genome sequencing geneticists should report to physicians and which results should be passed on to patients, geneticists say. Also lacking is clear guidance on who should have access to the findings, such as a patients employer or relatives who could share some of the same genes.
Genome sequencing to add new twist to doctor-patient talks
On March 29, 2012, Oracle announced that it has agreed to acquire ClearTrial, a leading provider of cloud-based Clinical Trial Operations and analytics products that make the planning, sourcing, and tracking of clinical projects and financial performance…
30-03-2012 11:44 Personalized medicine is becoming an increasingly important aspect of cancer treatment. Levi Garraway, MD, PhD, of Dana-Farber Cancer Institute and the Broad Institute, describes a new database of nearly 1000 cancer cell lines, across numerous tumor types, that will be used to help predict the effectiveness of cancer drugs based on a tumor's genetic profile.
ScienceDaily (Mar. 29, 2012) Developed in Canada and conducted by researchers from the University of Ottawa Heart Institute (UOHI), in partnership with Spartan Bioscience, the world's first bedside genetic test has received acknowledgment by The Lancet.
The article "Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial," reports on the use of a simple cheek swab test, the Spartan RX CYP2C19, performed by nurses at the patient's bedside. This revolutionary technology allows doctors to rapidly identify patients with a genetic variant known as CYP2C19*2. Cardiac stent patients with this variant are at risk of reacting poorly to standard anti-platelet therapy with Plavix (clopidogrel).
The study demonstrated that tailored drug treatment therapy made possible by the genetic testing successfully protected all of the patients with the at-risk genetic variant from subsequent adverse events, while 30 per cent of patients treated with standard therapy did not receive adequate protection.
"For the first time in medicine, nurses were able to perform DNA testing at the patient's bedside. This is a significant step towards the vision of personalized medicine," said Dr. Derek So, Interventional Cardiologist at the University of Ottawa Heart Institute (UOHI), and principal investigator of the RAPID GENE study.
The RAPID GENE study enrolled 200 patients who were being treated with cardiac stenting for an acute coronary syndrome or stable angina. Patients were randomized to a treatment strategy of rapid point-of-care genotyping and Effient (prasugrel) for CYP2C19*2 carriers, or to standard therapy with Plavix (clopidogrel). The Spartan RX CYP2C19 bedside DNA test was performed by nurses who received a 30-minute training session, but had no prior laboratory training. The test had a sensitivity of 100% and a specificity of 99.4% compared with DNA sequencing. For CYP2C19*2 carriers, treatment with prasugrel completely eliminated High on-treatment Platelet Reactivity (HPR). HPR is a marker for patients at risk of complications after stenting. In contrast, 30.4% of carriers receiving clopidogrel had HPR at 1 week.
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The above story is reprinted from materials provided by University of Ottawa Heart Institute.
Originally posted here:
World's first bedside genetic test
Published: March. 29, 2012 at 11:18 PM
DALLAS, March 29 (UPI) -- U.S. researchers say they have developed a lifesaving genetic screening program for families at high risk of contracting colorectal cancer.
Dr. Samir Gupta, assistant professor of internal medicine at the University of Texas Southwestern in Dallas, who is also head of the high-risk colorectal cancer clinic, said colorectal cancer is the second-leading killer after lung cancer -- and while hereditary colorectal cancer is rare, its family impact can be widespread.
Cancer tends to develop rapidly in those with Lynch syndrome, one of the more common inherited conditions. Lynch syndrome accounts for 3 percent to 5 percent of all colon cancers, and often is undiagnosed until the disease is advanced.
Families that have Lynch syndrome usually have more cases of colon cancer than would typically be expected, and at an earlier ages, than in the general population.
Gupta said doctors screen the tumors of colorectal cancer patients younger than age 70 and uterine cancer patients younger than age 55 to determine whether there is a high risk of a genetic cancer predisposition. If so, patients are encouraged to bring in as many family members as possible for testing, Gupta said.
"If we can bring in family members, we have a chance to catch their colon cancer early and even prevent it," Gupta said in a statement.
Patients with Lynch syndrome have an 80 percent risk of contracting colorectal cancer and as much as a 60 percent risk for uterine cancer, and higher than average risks for other cancer types, Gupta added.
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Genetic screenings detect at-risk families