Category Archives: Genetic Medicine

First Bedside Genetic Test Could Prevent Heart Complications

A genotyping test from a Canadian biotech company enables timely personalized drug treatment.

For some cardiac patients, recovery from a common heart procedure can be complicated by a single gene responsible for drug processing. The risk could be lowered with the first bedside genetic test of its kind. The test shows promise for quickly and easily identifying patients who need a different medication.

Quick test: This shoebox-sized device from Spartan Bioscience supports the first bedside genetic test. Spartan Bioscience

After a patient receives a heart stenta small scaffold that props open an arteryhis or her doctor will prescribe a blood thinner to prevent platelets from building up inside the device. However, for some 70 percent of patients with Asian ancestry and 30 percent of patients with African or European ancestry, a single genetic variant will prevent one of the most commonly prescribed blood thinners from working. Alternatives exist, but they are more expensive, so hospitals could use an easy way to identify who does and does not need the more expensive drug.

Canada's Spartan Biosciencehas developed a near "plug-and-play" genotyping device that allows nurses and others to quickly screen patients at the bedside, perhaps while they are undergoing the stent placement procedure. Users take a DNA sample from a patient's cheek with a specialized swab, add the sample to a disposable tube, and then place the tube and sample in a proprietary shoebox-sized machine and hit a button. Shortly thereafter, the user receives a printout of the patient's genetic status for the drug-processing variant. The whole procedure takes about an hour. Most clinicians currently have to wait several days for similar information to come from off-site genetics testing companies.

"For six years we've been plugging away at this, and we finally broke through about a year and a half ago," says Spartan Bioscience founder Paul Lem. He says the simple test came to life with innovations at every stepfrom the special swab that collects the right amount of DNA, to the chemicals in the disposable reaction tube, to the software that automates the DNA readingand a team with diverse backgrounds including his in medicine and molecular biology and others' in optical hardware.

Lem has kept an eye on other companies trying to create a bedside genetic test, some going after the same variant, and calculates that over $1 billion in capital has been spent over the last five years in this area.

The University of Ottawa Heart Institute researchers conducted a proof-of-principle trial for the device and found that the bedside test is effective at quickly identifying carriers of the drug-processing variant and can be performed by nurses with minimal training. The findings were published in The Lancet last week.

"The stakes are pretty high" for the risks associated with the variant in the test, says Euan Ashley, a cardiologist with Stanford's Center for Inherited Cardiovascular Disease. Patients who receive a stent implant after a heart attack or as a preventive measure are at risk for serious adverse events if their bodies cannot process a commonly prescribed anti-platelet drug into its active form. "There's a startling number of people who carry the variant, which leaves them at risk," says Ashley. "Being able to get an answer within an hour or twowhen you are thinking of a patient's heartis a pretty compelling case for [testing for it]."

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First Bedside Genetic Test Could Prevent Heart Complications

Public release date: 4-Jun-2012 [ | E-mail | Share ]

Contact: Mary Jane Gore mary.gore@duke.edu 919-660-1309 JAMA and Archives Journals

CHICAGO A 38-year longitudinal study of New Zealanders suggests that individuals with higher genetic risk scores were more likely to be chronically obese in adulthood, according to a report published in the June issue of Archives of Pediatrics & Adolescent Medicine, a JAMA Network publication.

Obesity is capable of being inherited and genome-wide association studies (GWASs) have started to uncover the molecular roots of heritability by identifying multiple single-nucleotide polymorphisms (SNPs) associated with higher adult body mass index (BMI), the authors write in their study background.

"In this study, we asked how SNPs with replicated GWAS evidence for association with adult BMI relate to growth across the first four decades of life and to adult obesity in a birth cohort followed up prospectively from birth through 38 years of age," Daniel W. Belsky, Ph.D., of Duke University, Durham, N.C., and colleagues write in the study background.

Study participants were members of the Dunedin Multidisciplinary Health and Development Study, an investigation of health and behavior in a complete birth cohort. The 1,037 study members (52 percent were male) were born between April 1972 and March 1973 in Dunedin, New Zealand. Assessments were performed every few years starting at birth until 38 years.

Children with higher genetic risk scores (GRSs) had higher BMIs at every age assessed from age 3 through 38 years. Children at high genetic risk were 1.61 to 2.41 times more likely to be obese in their second, third and fourth decades of life and were 1.90 times more likely to be chronically obese across more than three assessments compared with children at low genetic risk, according to study results.

Adiposity rebound, when children begin to gain body fat after losing it during early childhood, occurred earlier in development and at higher BMI for children at higher genetic risk, the results indicate.

Higher genetic risk also predicted faster growth and increased obesity risk in children with normal-weight and overweight parents, the study results note. The authors comment that the GRS contributed "independent and additive information" to the prediction of children's growth and their risk for obesity in adulthood beyond the family history information.

"Thus, the results present compelling evidence that SNPs identified in GWASs of adult BMI and other obesity-related phenotypes predispose to more rapid growth in childhood, leading to increased risk for obesity in adulthood, and provide information not forthcoming from a simple analysis of family history," the authors conclude.

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Genetics, rapid childhood growth and the development of obesity

Washington, June 2 : Lean type 2 diabetes patients have a larger genetic disposition to the disease as compared to their obese counterparts, a new study has proved.

Type 2 diabetes is popularly associated with obesity and a sedentary lifestyle. However, just as there are obese people without type 2 diabetes, there are lean people with the disease.

It has long been hypothesised that type 2 diabetes in lean people is more "genetically driven".

The study, from a research team led by the Peninsula College of Medicine and Dentistry (PCMD), University of Exeter, has also identified a new genetic factor associated only with lean diabetes sufferers.

Using genetic data from genome-wide association studies, the research team tested genetic markers across the genome in approximately 5,000 lean patients with type 2 diabetes, 13,000 obese patients with the disease and 75,000 healthy controls.

The team found differences in genetic enrichment between lean and obese cases, which support the hypothesis that lean diabetes sufferers have a greater genetic predisposition to the disease.

This is in contrast to obese patients with type 2 diabetes, where factors other than type 2 diabetes genes are more likely to be responsible. In addition, genetic variants near the gene, LAMA1, were linked to type 2 diabetes risk for the first time, with an effect that appeared only in the lean patients.

"Whenever a new disease gene is found, there is always the potential for it to be used as a drug target for new therapies or as a biomarker, but more work is needed to see whether or not this new gene has that potential," John Perry, one of the lead authors of the study, said.

"This is the first time that a type 2 diabetes gene has been found to act in this way we do not know why it should be associated in one sub-group of patients and not another.

"It could point to the fact that type 2 diabetes may not be one disease, but may represent a number of subgroups. Again, more work is required to prove this hypothesis.

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New genetic factor associated with lean diabetics identified

In a lab in Atlanta, a group of flies is sleeping fitfully. Their naps are fragmented, and their legs are twitching. Their behaviour is uncannily similar to people who have a condition called restless leg syndrome (RLS). When such people are awake, they experience uncomfortable sensations in their limbs that compel them to move to get some relief. Their sleep, which is fragmented and disturbed, is characterised by the same involuntary movements.

Theres a good reason for these similarities. Amanda Freeman from the Emory University School of Medicine has engineered the flies so that they have a faulty copy of BTBD9, a gene that has been linked to RLS in humans. The fact that they show the same constellation of symptoms strongly suggests that this gene is genuinely involved in the condition.

In 2007, two teams of scientists linked BTBD9 to the repeated limb movements that occur during RLS. A single change in the genes sequence increased the risk of such movements by more than 50 per cent, and was probably involved in around half of such cases. One of the teams wrote that the discovery provides evidence that periodic limb movements in sleep is a genuine syndrome with a detectable genetic basis. Thats important, especially since critics have suggested that many RLS cases are the product of disease-mongering by the pharmaceutical industry in order to sell more drugs.

But showing a correlation between a gene and a symptom is just the first step. You also need to work out what the gene is doing and that was unclear. The gene was switched on throughout the brain, but no one really knew what it did. Freeman has gone some way to solving that mystery, and cementing BTBD9s connection with RLS, by studying fruit flies.

Flies also have a version of BTBD9, which is also switched on throughout the nervous system. When Freeman mutated the gene so it could no longer be used, it affected how the flies slept. (Like use, flies stay still for distinct periods throughout the day, when they become unresponsive to the outside world; if theyre deprived of such bouts, they need more rest later.) Those with inactive copies of BTBD9 slept for the same amount of time as normal flies, but in fragmented bouts.

They also walked more during their sleep, moving their limbs in a way that mirrored the restlessness of people with RLS. In the video above, the flies in the blue lanes are normal, while those in the red lanes are the mutants. Note how much more active they are.

This suggests that the original human studies were pointing in the right direction, says Subhabrata Sanyal, who led the new research. However, he cautions that it is too early to say whether this gene does exactly the same things in flies and humans. The symptoms look superficially similar, but theyre not an exact match. People with RLS also rhythmically flex their feet, something that Sanyal says is virtually impossible to see in flies.

On top of that, we still understand very little about RLS as a human condition. Its diagnosis involves a questionnaire rather than a clinical test, and its still unclear if it is one syndrome with a consistent set of symptoms, or many. It is conceivable that not all RLS patients have the same disorder, says Sanyal.

This is another area where basic science could help. In humans, RLS has been linked to a lack of dopamine (a signalling chemical in the brain), and a deficiency of iron. Freeman found evidence to support both ideas. Her mutant flies had around half as much dopamine in their brains as normal ones, and they slept more soundly once she gave them a dopamine-boosting drug. In human cells, she also found that BTBD9 controls the levels of ferritin, a protein that stores and releases iron.

Its a start, and Sanyal emphasises that its a tiny step. He also wants to study the role of the gene in rodents, and he suspects that it is involved in a process called ubiquitination, where small chemicals are attached to proteins to control where they are sent and when they are destroyed. Studying [BTBD9] in much greater detail is necessary to understand exactly what it does in neurons, he says.

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Mutant flies confirm genetic link to restless legs syndrome | Not Exactly Rocket Science

As the cost of mapping out personal genomes goes down, the more potentially lifesaving but sensitive genetic data is available. Although the day when its commonplace to have that personal information in a medical record may be several years away, it is coming. And health insurers and hospitals need to think about how that information will be processed and transmitted in electronic medical records.

The Air Force Medical Service is collaborating with personalized medicine research center, the Coriell Institute for Medical Research in Camden, New Jersey in a study to review and evaluate medical evidence assess, among other things, best practices for using genetic information in EMRs, according to Coriell President Dr. Michael Christman. It will look at how the data should be displayed and how it should be shared with physicians.

About 2,000 active duty medical service personnel are expected to participate in the six-year Patient-Centered Precision Care Research program longitudinal study. It has already begun the recruitment process. Johns Hopkins University Applied Physics Laboratory will also offer research and program management support for the study.

The institute is working on a similar study with Ohio State University Medical Center.

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Personalized medicine study using genetic data in EMRs signs up Air Force

30-05-2012 10:32 Nicolas H. Zech, Congress President Where to next for PGD? From polar body to blastocyst -- the evolving genome Dear Colleagues! On behalf of the Preimplantation Genetic Diagnosis International Society (PGDIS) we take great pleasure in inviting you to our biannually held 11th International Conference in Bregenz, Austria. The PGD Conference will address a much wider range of topics than PGD, as the recent developments in related areas may soon move PGD from a research tool to the basic procedure in reproductive medicine and genetic practices. First of all, the recent application of microarray technology and next generation sequencing may clearly improve the accuracy of PGD for genetic and chromosomal disorders, so array-CGH, SNP arrays, genome wide analysis and next generation sequencing for single cell analysis will be one of the major topics of the Conference. In addition some related theoretical issues, such as molecular aspects of meiosis and cell fate in the preimplantation embryo will be also addressed. On the other hand, because of increasing importance of clinical aspects of PGD, a number of Workshops will be organized on advance topics in clinical PGD, as well as a few debates on controversial issues in PGD, such as the optimal stage for performing biopsy procedures and reproductive outcome of preimplantation aneuploidy testing, prior to and after the application of 24-chromosome analysis, currently performed in a few dozens of thousands of cycles. As PGD is still ...

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11th International Conference on Preimplantation Genetics Diagnosis Welcome remarks Nicolas H. Zech - Video