Genetics
Genes affect weight loss drug effectiveness
A study conducted by researchers at Mayo Clinic shows that obese patients with specific genetic makeup had enhanced response to the weight loss drug sibutramine, while others who lack these genetic factors lost little or no weight.
The findings are published in the October issue of Gastroenterology (http://www.gastrojournal.org).
In this randomized, double-blind, placebo-controlled study, Mayo researchers measured the impact of two different dosage levels of sibutramine (10 or 15 mg daily) combined with behavioral therapy for 12 weeks in 181 overweight or obese participants. Participants received structured behavioral therapy for weight management at four, eight and 12 weeks.
The first autism disease genes
The autistic disorder was first described, more than sixty years ago, by Dr. Leo Kanner of the Johns Hopkins Hospital (USA), who created the new label ´early infantile autism´. At the same time an Austrian scientist, Dr. Hans Asperger, described a milder form of the disorder that became known as Asperger Syndrome, characterised by higher cognitive abilities and more normal language function. Today, both disorders are classified in the continuum of ´Pervasive Developmental Disorders´ (PDD), more often referred to as Autism Spectrum Disorders (ASD).
The prevalence of (classic) autism in the general population is about 15-20 in 10.000, while all Autism Spectrum Disorders (ASD) affect about 60 in 10.000 children. Males are affected four times more often than females. In approximately 10% of cases, autism is associated with a recognized cause, such as Fragile X Syndrome, Tuberous Sclerosis or diverse chromosomal abnormalities (mean observed rates between 5-10%), but in a vast majority of cases, no known causes are associated with autism.
Gene variant common in Africa increase HIV risk
A gene variant that emerged thousands of years ago to protect Africans from malaria may raise their vulnerability to HIV infection but help them live longer once infected, researchers said on Wednesday.
The findings could help explain why AIDS has hit Africa harder than all other parts of the world.
People with the version of the gene have a 40 percent higher risk of becoming infected with the human immunodeficiency virus, or HIV, researchers in the United States and Britain wrote in the journal Cell Host & Microbe.
Known Genetic Risk for Alzheimer’s in Whites Also Places Blacks at Risk
A commonly recognized gene that places one at risk for Alzheimer’s disease does not discriminate between blacks and whites, according to new research led by Florida State University.
FSU Psychology Professor Natalie Sachs-Ericsson and graduate student Kathryn Sawyer have found that the gene APOE epsilon 4 allele is a risk factor for African-Americans as well as whites. Until now, it has been a mainstream belief that the gene is only a risk factor for whites.
“The results of our study have clear implications for research and treatment of Alzheimer’s disease,” Sachs-Ericsson said. “The APOE test might be used as one tool in identifying people who are at risk for Alzheimer’s. We now know that African- Americans and Caucasians alike need to be considered for such risk assessments.”
First gene therapy for heart failure offered at NewYork-Presbyterian/Columbia
Could injecting a gene into a patient with severe heart failure reverse their disabling and life-threatening condition? Physician-scientists are setting out to answer that question in a first-ever clinical trial of gene therapy to treat severe heart failure.
NewYork-Presbyterian Hospital/Columbia University Medical Center is the only center in the New York City area where the therapy is currently available.
Patients enrolled in the multicenter CUPID trial (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease) will undergo a minimally invasive cardiac catheterization procedure that will introduce a specially engineered gene that stimulates production of an enzyme necessary for the heart to pump more efficiently.
Genetic cause for type of childhood epilepsy identified
Scientists have identified the mutated gene responsible for development of a type of epilepsy called childhood absence epilepsy, or CAE.
The condition is associated with frequent “absent” seizures where the patient’s consciousness is impaired leaving the child staring blankly ahead not aware or responsive for up to 10 seconds at a time. An inherited disorder, CAE accounts for 10 to 12 percent of epilepsy in children under age 16. CAE often disappears in adulthood.
The scientists studied the DNA of 48 patients with CAE and discovered that 4 patients had a genetic mutation occurring in the GABA receptor, which binds to a neurotransmitter of the brain called GABA that inhibits the excitation of nerve cells. When this regulation is lost or reduced, seizures develop.
Genetic links to impaired social behavior in autism
Individuals with autism spectrum disorders (ASD) show profound deficits in social interactions and communications, and display repetitive behaviors and abnormal responses to sensory experiences. One aspect of an autistic child’s impaired social abilities is their lack of affiliative behaviors, i.e., behaviors such as touching and hugging that strengthen social bonds. On May 15th, Biological Psychiatry is publishing an article that reports new findings on genetic bases of these behaviors.
In this study, Yale University researchers recruited, genotyped, and clinically assessed a large sample of autistic children and their families. They specifically examined the genetic variants in six genes known to be involved in maternal and affiliative behaviors. Dr. Elena Grigorenko, the senior author, discusses their study, “Animal studies have taught us that genetic factors can play a crucial role in the development of close affiliative ties. With the help of Yale’s Autism Center of Excellence, led by Drs. Ami Klin and Fred Volkmar, and many families of individuals with ASD, we have registered a possible association between some of the genes identified in animal studies as controlling affiliative behaviors in ASD.” The strongest statistical findings of the study implicate the prolactin gene, the prolactin receptor gene, and the oxytocin receptor gene in these affiliative behavior deficits.
Human ageing gene found in flies
Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have found a fast and effective way to investigate important aspects of human ageing. Working at the University of Oxford and The Open University, Dr Lynne Cox and Dr Robert Saunders have discovered a gene in fruit flies that means flies can now be used to study the effects ageing has on DNA. In new work published today in the journal Aging Cell, the researchers demonstrate the value of this model in helping us to understand the ageing process. This exciting study demonstrates that fruit flies can be used to study critical aspects of human ageing at cellular, genetic and biochemical levels.
Dr Lynne Cox from the University of Oxford said: “We study a premature human ageing disease called Werner syndrome to help us understand normal ageing. The key to this disease is that changes in a single gene (called WRN) mean that patients age very quickly. Scientists have made great progress in working out what this gene does in the test tube, but until now we haven’t been able to investigate the gene to look at its effect on development and the whole body. By working on this gene in fruit flies, we can model human ageing in a powerful experimental system.”
British team finds two genes for osteoporosis
British researchers have identified two common genetic mutations that increase the risk of osteoporosis and related bone fractures, according to a study released on Tuesday.
These changes were present in 20 percent of the people studied and highlight the potential role of screening for the bone-thinning disease that mainly affects women after menopause, they reported in The Lancet medical journal.
“Eventually, a panel of genetic markers could be used in addition to environmental risk factors to identify individuals who are most at risk for osteoporotic fractures,” Tim Spector and Brent Richards, researchers at King’s College London wrote.
Tiny magnets used in anti-cancer gene therapy
Tiny magnets have been used to deliver anti-cancer gene therapy in mice in a development that could make the treatment much more effective, scientists said on Thursday.
The idea behind gene therapy is to replace faulty genes. But the approach has had mixed success because of the difficulty of getting genes to the right part of the body.
One option is to use viruses to carry genes, but this increases the risk of triggering an immune system reaction.
Gene therapy reduces cocaine use in rats
Researchers at the U.S. Department of Energy’s Brookhaven National Laboratory have shown that increasing the brain level of receptors for dopamine, a pleasure-related chemical, can reduce use of cocaine by 75 percent in rats trained to self-administer it. Earlier research by this team had similar findings for alcohol intake. Treatments that increase levels of these chemicals - dopamine D2 receptors—may prove useful in treating addiction, according to the authors. The study will be published online April 16 and will appear in the July 2008 issue of Synapse.
“By increasing dopamine D2 receptor levels, we saw a dramatic drop in these rats’ interest in cocaine,” said lead author Panayotis (Peter) Thanos, a neuroscientist with Brookhaven Lab and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory of Neuroimaging. “This provides new evidence that low levels of dopamine D2 receptors may play an important role in not just alcoholism but in cocaine abuse as well. It also shows a potential direction for addiction therapies.”
HDL-Associated Protein Gene Linked to Heart Disease Risk
The gene for the HDL-associated protein paraoxonase 1 (PON1) appears to be associated with coronary artery disease and with the risk of developing adverse cardiac events, and variations in both the PON1 gene and its related enzyme activity may increase the risk for cardiovascular disease events, according to a study in the March 19 issue of JAMA, a theme issue on Genetics and Genomics.
Stanley L. Hazen, M.D., Ph.D., of the Cleveland Clinic, presented the findings of the study at a JAMA media briefing at the National Press Club in Washington, D.C.
Despite evidence that PON1 prevents atherosclerosis in animals, a cardio-protective role in humans has not been established. Several studies have suggested that PON1 may have antioxidant and cardio-protective properties, according to background information in the article.
Geneticist First to Connect a Gene Central to Neuron Formation to Autism
Eli Hatchwell, M.D., Ph.D., Associate Professor of Pathology at Stony Brook University Medical Center, and colleagues have found that a disruption of the Contactin 4 gene on chromosome 3 may be linked to autism spectrum disorder (ASD). What causes ASD, a developmental disorder of the central nervous system, is largely unknown. Dr. Hatchwell’s finding suggests that mutations affecting Contactin 4 may be relevant to ASD pathogenesis, and thus a potential biomarker for some individuals with the disorder. Details of the study are reported in the early online edition of the Journal of Medical Genetics.
According to the Centers for Disease Control and Prevention, the prevalence of ASD in the United States may be as high as 1 in 150 children. The disorder is divided into five subtypes, including autism proper. Pathogenesis of ASD may be environmental and/or biological. Experts suspect that many genes may play a role in the etiology of ASD.
Variations of Stress Response Gene Appear To Be Predictive of Risk of PTSD
Adults who experienced child abuse and have variations of a gene related to stress response appear to be at greater risk of posttraumatic stress disorder symptoms as adults, according to a study in the March 19 issue of JAMA, a theme issue on Genetics and Genomics.
Rebekah G. Bradley, Ph.D., of the Emory University School of Medicine, Atlanta, presented the findings of the study at a JAMA media briefing at the National Press Club in Washington, D.C.
“Posttraumatic stress disorder (PTSD) is a debilitating stress-related psychiatric disorder, with prevalence rates of at least 7 percent to 8 percent in the U.S. population, and with much higher rates among combat veterans and those living in high-violence areas. Initially viewed as a potentially normative response to traumatic exposure, it became clear that not everyone experiencing trauma develops PTSD. Thus, a central question in research on PTSD is why some individuals are more likely than others to develop the disorder in the face of similar levels of trauma exposure,” the authors write. They add that it is becoming clear that there are critical roles for pre-disposing genetic and environmental influences in determining the psychological risk to the traumatized individual, with child abuse appearing to provide significant risk for the development of PTSD.
Gene Hunters Fine-Tune Marker for Common Obesity Gene
Genomics researchers, seeking to replicate another group’s discovery of an important gene associated with obesity, have further refined the signal to a particular variant in DNA that may be more helpful in identifying this gene’s role in obesity in various human populations worldwide. The finding suggests that the gene variant, identified in DNA from African American children, may be a tag of an ancient mutation that first arose in Africa, where humans originated.
The research team, led by Struan Grant, Ph.D., and Hakon Hakonarson, M.D., Ph.D., both of the Center for Applied Genomics of The Children’s Hospital of Philadelphia, was studying the FTO gene, identified by a British group in 2007 as raising the risk of adult and childhood obesity. Although environmental influences are certainly important, family studies have indicated that obesity has a genetic component as well.
The research team, from Children’s Hospital and the University of Pennsylvania School of Medicine, reported its findings in the March 12 issue of the journal Public Library of Science ONE.
