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Posts Tagged ‘gene’

Mutant gene causes epilepsy, intellectual disability in women

A mutated gene has been discovered as the key behind epilepsy and mental retardation specific to women, thanks to new research at Adelaide’s Women’s & Children’s Hospital and the University of Adelaide, Australia.

The world-first discovery, published today in Nature Genetics, shows that although men carry the ‘bad’ gene, only women are affected.

The research has been led by Dr Leanne Dibbens and Associate Professor Jozef Gecz from the Department of Genetic Medicine, Women’s & Children’s Hospital, and the Discipline of Paediatrics at the University of Adelaide. The discovery is a result of a major international collaboration involving the Sanger Institute in Cambridge (UK), Wellcome Trust (UK) and many other collaborators in Australia, the United States, Ireland and Israel. … Continue Reading »

Second genetic link to weight and obesity

New DNA variants found that can help to pile on the pounds

A study of 90,000 people has uncovered new genetic variants that influence fat mass, weight and risk of obesity. The variants act in addition to the recently described variants of the FTO gene: adults carrying variants in both genes are, on average, 3.8 kg (or 8.5 lb) heavier.

The variants map close to a gene called MC4R: mutations in this gene are the most common genetic cause of severe familial obesity. The study highlights the power of large collections of volunteer samples to uncover common variants that influence health.

“By working together with many international groups we have been able to assemble a sample collection which was large enough to allow this finding to be made,” explains Dr Ruth Loos, leading author from the Medical Research Council Epidemiology Unit. “Several groups had shown that rare, highly disruptive variants in the MC4R gene were responsible for very severe, genetic forms of obesity: this collaboration has uncovered more common variants that affect more people.”

The study, published in Nature Genetics, is led by investigators from the Cambridge GEM consortium (Genetics of Energy Metabolism) and Oxford University and is a collaboration between 77 institutions from the UK, USA, France, Germany, Italy, Finland and Sweden.

The team studied more than 77,000 adults and found that two copies of genetic variants resulted in an average increase in weight of about 1.5 kg.

This is the second set of common variants that are associated with weight and obesity, following the study, involving many of the same team, published in April 2007 that uncovered a role for the FTO gene. People who carry two copies of an FTO variant are about 2-3 kg heavier than those who have no copies of the variant.

Importantly, the effects of the new gene add to those of FTO; people who carried both the FTO variant and new variants were on average 3.8 kg (8.5 lb) heavier.

“This is a great example of how cooperation can bring about new findings that can be missed when researchers work in isolation,” explains Dr Inês Barroso, Investigator at the Wellcome Trust Sanger Institute and one of the senior authors on the study. “The precise role in obesity of genetic variants in FTO and near MC4R remains to be discovered, but we can now begin to understand the biological consequences of these variants. This is where this research will make a difference.”

MC4R protein plays a pivotal role in many aspects of physiology, including regulation of appetite and energy expenditure. The severe form of MC4R-related obesity is a consequence of alterations in the gene sequence, resulting in an inactive or less active MC4R protein.

By contrast, the new variants lie some distance from the MC4R gene. The team suspect that the sequence variant changes activity of the MC4R gene, perhaps by disrupting DNA regions required for normal activity of MC4R.

“Through this new and powerful genetic approach we are increasingly finding that the genes known to play a role in severe – but rare – diseases are also implicated in much more common disease,” explains Professor Mark McCarthy, Robert Turner Professor of Diabetes at the University of Oxford, UK. “The common variants we are uncovering do not have such a dramatic effect on the normal functioning of the gene as do the rare mutations in MC4R that can cause rare examples of very serious, early onset obesity.”

Dramatically, in a study of almost 6000 children, they found that the effects were almost double those seen in adults. Between the ages of four and seven, this additional increase in weight was the result, almost exclusively, of gain of fat tissue, and not due to gain in muscle or other solid tissues.

This more dramatic effect in young children reflects the more extreme consequences seen with rare variants of MC4R that severely disrupt its activity, suggesting that the novel variants do indeed exert their effect through action on MC4R.

“Our work to understand common disease, such as obesity, depends on the participation of thousands of people – members of the public who provide samples,” explains Professor Nick Wareham, Director of the MRC Epidemiology Unit. “Without their willing participation, we could never achieve the power in our research to make striking findings like this.

“For each discovery, our efforts and the contribution of the participants will lead to improved healthcare for the population at large.”

The team will now look to uncover how the DNA variants affect activity of the MC4R protein, which is a key player in orchestrating information from the body to control appetite and energy expenditure to keep body weight in balance. The team propose that altered activity of MC4R, imposed by the variants, might reduce its ability to carry out this important role.

The team emphasize that, although gene variants can affect weight, body mass index and obesity, they are only part of the story: lifestyle actions such as good diet and regular exercise are vital to control of weight.

Source: Wellcome Trust Sanger Institute

Loos RJF et al. (2008) Association studies involving over 90,000 people demonstrate that common variants near to MC4R influence fat mass, weight and risk of obesity. Nature Genetics Published online on Sunday 4 May 2008.

A tall story: New research adds to growing body of knowledge of genetics of height

Scientists are beginning to develop a clearer picture of what makes some people stand head and shoulders above the rest. A team of researchers who last year identified the first common version of a gene influencing height has now identified a further twenty regions of the genome which together can make a height difference of up to 6cm.

The results, published together with two independent studies online today in the journal Nature Genetics, mean that scientists now know of dozens of genes and genetic regions that influence our height. This provides scientists with a fascinating insight into how the body grows and develops normally and may shed light on diseases such as osteoarthritis and cancer. … Continue Reading »

Researchers uncover new genetic links to psoriasis

In the first comprehensive study of the genetic basis of psoriasis, researchers at Washington University School of Medicine in St. Louis have discovered seven new sites of common DNA variation that increase the risk of the troublesome skin condition. They also found that variations in one genetic region link psoriasis and a related joint disorder, psoriatic arthritis, to four autoimmune diseases: type 1 diabetes, Grave’s disease, celiac disease and rheumatoid arthritis.

The study’s results appear April 4 in the open-access journal PLoS Genetics.

“Common diseases like psoriasis are incredibly complex at the genetic level,” says lead investigator Anne Bowcock, Ph.D., professor of genetics at the School of Medicine. “Our research shows that small but common DNA differences are important in the development of psoriasis. Although each variation makes only a small contribution to the disease, patients usually have a number of different genetic variations that increases their risk of psoriasis and psoriatic arthritis.” … Continue Reading »

Researchers ID gene linked to lung cancer

Researchers at Johns Hopkins, as part of a large, multi-institutional study, have found one gene variant that is linked to an increased risk of lung cancer. The study will be published in the April 3 issue of Nature Genetics.

The research team collected DNA from 1,154 smokers who have lung cancer and 1,137 smokers without lung cancer. Each DNA sample was analyzed at more than 300,000 points, looking for variations—known as single nucleotide polymorphisms, or SNPs for short—between those with cancer and those without. They then analyzed the top 10 SNPs in an additional 5,075 DNA samples from smokers with and without lung cancer. … Continue Reading »

Joslin researchers discover new effect for insulin

Researchers at the Joslin Diabetes Center have shown that insulin has a previously unknown effect that plays a role in aging and lifespan, a finding that could ultimately provide a mechanism for gene manipulations that could help people live longer and healthier lives.

The paper, published in the March 21st issue of Cell, reports that insulin inhibits a master gene regulator protein known as SKN-1, and that increased SKN-1 activity increases lifespan. SKN-1 controls what is called the Phase 2 detoxification pathway, a network of genes that defends cells and tissue against oxidative stress – damage caused by elevated levels of free radicals (byproducts of metabolism) – and various environmental toxins. The new finding was demonstrated in experiments on the digestive system of C. elegans, a microscopic worm often used as a model organism.

“We’ve found something new that insulin does and it has to be considered when we think about how insulin is affecting our cells and bodies,” said Dr. T. Keith Blackwell, senior investigator at Joslin and author of the paper. “This has implications for basic biology since under some circumstances insulin may reduce defense against the damaging effects of oxidative stress more than we realize.”

The idea down the line is that fine-tuning the activity of SKN-1 may lead to increased resistance to chronic diseases and influence longevity, he said. The work could be important as it relates to diabetes and the many problems associated with the disease, particularly vascular and renal complications.

But, today’s finding may be most important for what it teaches about aging in general, he said. … Continue Reading »

Promising research on the susceptibility to and drug targets for Parkinson’s disease

Better understanding of Parkinson’s disease onset during aging is important for improving diagnostics and developing strategies for therapeutic intervention. Scientists from the University Medical Center in Groningen have now identified genes and processes that may underlie what makes some people more susceptible to this disease. Their findings are described in an article published March 21 in the open-access journal PLoS Genetics.

On average, the population of the western world is living longer, resulting in an increased number of people with age-related neurological conditions, including Alzheimer’s and Parkinson’s disease. A cure for these diseases remains elusive because their molecular cause is only partially understood. It has been noted, however, that accumulations of folded proteins are commonly found within the brain cells of those who suffer from these diseases. For this reason “protein misfolding” seems to form the basis of these diseases. … Continue Reading »

‘Jumping gene’ may contribute to a premature aging syndrome

Scientists have identified a fusion protein that may contribute to Cockayne syndrome, a devastating disease characterized by developmental defects, neurodegeneration, severe wasting, and premature aging. The study is described in an article published March 21 in the open-access journal PLoS Genetics.

Genetic defects in certain DNA repair factors like the CSB protein have been known for some time to cause premature aging, but the reasons are still unclear. Most cases of Cockayne syndrome (CS) are caused by recessive mutations in the CSB gene, yet some individuals with inherited mutations that cause complete loss of the CSB protein are nearly unaffected. The implication is that CS is not caused solely by loss of functional CSB protein, but by continued expression of CSB-related proteins or protein fragments. … Continue Reading »