Change genetic destiny of your heart with a better lifestyle

ulrik-wisloffA new study published on Sunday in the prestigious New England Journal of Medicine investigated more than 55000 people to answer the question if genetics is synonymous with destiny when it comes to developing heart disease or whether the risk can be offset by a healthy lifestyle.

The study found that those with even the worst genetic risk, but a favorable lifestyle (defined not smoking, eating a diet rich in fruits, grains and vegetables and exercising moderately) had a 50% lower risk of developing heart disease than those with high genetic risk but unfavorable lifestyle.

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Your blood can reveal your risk for heart disease

Researcher at CERG, Anja ByeWhen you visit your general practitioner you can get your blood analyzed for cholesterol and triglycerides, to get an idea of your risk for cardiovascular disease. With additional information about BMI, smoking habits and blood pressure, this can be used to calculate your 10-year risk for cardiovascular disease. There are several risk prediction calculators available today that general practitioners can use the before they give advice and prescriptions to their patients. This risk calculators predicts the 10-year risk for dying form cardiovascular disease, and includes information on age, gender, smoking habits, systolic blood pressure and total cholesterol.

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Cas9: the gene hacker that bites DNA

Jose Bianco MoreiraEvolutionary pressures forced all living species to adapt to challenging and hostile environments. Giraffes developed long necks that enable them to reach more food on top of trees, birds can fly to escape dangers from ground level and humans became smart enough to domesticate their previous predators. These characteristics evolved over millions of years as a result of random DNA mutations, which somehow conferred survival advantage to an organism that would then pass this “good mutation” to the next generations. Although these DNA alterations (mutations) are necessary for the evolution of species, their random nature sometimes gives rise to unwanted characteristics. This is the case of genetic diseases that have haunted humanity for centuries.

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We hear about them all the time, but what is a gene?

Nathan ScrimeourWe hear about them all the time – this gene causes a disease, or that gene is important for normal heart function. Most people could tell you that your genes are made of something called DNA, that you inherit them from your parents and pass them on to your children, and that they determine much of who you are and what you look like. But how do we get from genes to an entire organism, and what control do we have over our genes?

To answer these questions, we need a basic understanding of what is known as the “central dogma” of biology, which describes the one way flow of genetic information. While the reality is more complex than this, the flow can be simplified as such:

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What is your cholesterol? – Know your number!

Elisabeth Vesterbekkmo. Foto: BERRE ASFamilial Hypercholesterolaemia (FH) is the most common of all severe familial disorders and its hallmark is high LDL-cholesterol in plasma. The disease is carried by one out of 200-300 persons in Europe – that is to say a total of about 2 million people in Europe carry FH. The disease is present from early childhood, but is carried without symptoms until the third or fourth decade in life, when heart disease will appear. If untreated, 50 percent of men will have had their first heart attack before the age of 50 years, and women before 55 years. To carry FH is to carry a ticking bomb that, if untreated, will cause cardiac disease or death.

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Exercise for a healthy brain

hjerne2Most people know that exercise is good for their physical health, but not everyone knows that it also has beneficial effects for cognitive functions and mental health. Cognitive performance decreases with old age, and a growing elderly population increases the amount of people that will get diseases such as dementia and Alzheimer’s. In addition, mood related disorders are a major worldwide problem. Exercise can improve the lives of people who are at the risk of developing these brain-associated disorders.

Exercise can increase your memory

A study performed on elderly people showed that increased physical activity resulted in an enhanced memory performance. It did not matter if the increased activity came from organized training sessions or from routines embedded into the daily life such as walking to the supermarket, take the stairs instead of the elevator, and generally move around more in the house. One of the symptoms of diseases such as dementia and Alzheimer’s is impaired memory, and regular aerobic exercise is therefore recommended to prevent or delay the onset of these diseases.

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Why do some people get fitter than others?

Two women running outdoorThe response to exercise training is often described in general terms, with the assumption that the group average represents a typical response for most individuals. However, in reality, it is more common for individuals to show a wide range of responses to identical exercise programs. In 1999, a large study published by Claude Bouchard and colleagues, reported that 20 % of us show little or no gain in maximal oxygen consumption (VO2max) with exercise training. This is a concern, since a high VO2max is associated with decreased rates of cardiovascular morbidity and mortality. Exploring the phenomenon of high responders and low responders following the same exercise program may provide helpful insights into mechanisms of training adaptation and methods of training prescription.

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Genetics and cardiovascular disease

Picture of DNAIn Western world, cardiovascular disease (CVD) is among the leading cause of premature death and a major cause of disability. Over the years, the knowledge of CVD risk factors clustering and their multiplicative interactions to promote CVD risk has led to the development of multivariable risk prediction algorithms to use in primary care settings. The guidelines for CVD prevention recommend that an individual’s risk of CVD is estimated by combining different risk factors into a numeric estimate of risk. Most of these risk prediction algorithms include well-known CVD risk factors such as: age, sex, hypertension, cholesterol, smoking, family history of CVD and diabetes mellitus. A variety of risk prediction algorithms are available, as charts, tables, computer programmes, and web-based tools.

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Tailored exercise for your DNA

DNA blåLes dette innlegget på norsk her!

Several research reports state that our genes play an important role in how each of us responds to different types of exercise. The first major study that showed variation in training response was published in 1980. In this study, 720 individuals participated in a training program that lasted five months, and the researchers measured the maximal oxygen uptake (the best measure of fitness) before and after the exercise period. Surprisingly, they saw a huge difference in changes of oxygen uptake. A few actually decreased while others increased tremendously.

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Targeted Nucleose Technology and knockout rats – guest lecture at NTNU

Yesterday Professor Aron Guerts from the Cardiovascular Research Center and Human Molecular Genetics Center at the Medical College of Wisconsin visited NTNU. Many of us visited his guest lecture, titled “Targeted Nuclease Technology: Empowering genetic engineering beyond the mouse”.

Over the past five to ten years, a suite of revolutionary tools has emerged and created a new field of “Genome Editing”. During the last 20 years, precision modification of a genome was basically restricted to the mouse model and their embryonic stem cells from a couple of common strains. Scientific progressions within the field have now made it possible to engineer precise mutations and genetic modifications to essentially any genome of any cell from any strain or species.

Photo: HeadSpin

Photo: HeadSpin

With the term Targeted Nuclease Technology (TNT), Guerts especially points to the three following discoveries:

  • The Zinc-Finger Nucleases (ZFNs), an artificial restricion enzyme improving the targeting of unique sequences within complex genomes.
  • Transcription activator-like effector nucleases (TALENs) – another restriction enzyme, generated by fusing a TAL effector DNA binding domain to a DNA cleavage domain. This type of enzymes cut DNA strands at a specific secuence. The advantage of transcription activator-like effectors (TALEs) is that they can be engineered to bind practically any desired DNA sequence. This enables genome editing when TALENs are introduced into cells.
  • RNA-Guided Nucleases (RGNs) (CRISPR/Cas9), programmable endonucleases also involved in targeted genome editing. 

These discoveries have vastly expanded the possibilities for both basic research of the genome and for promising therapeutic strategies. Guert’s research group at the Medical College of Wisconsin has explored the use of TNT to laboratory rat and mouse disease model strains to create resources of gene knock-out models, specific gene knock-in strains, and for generating conditional (Cre/loxP-based) knockout models.  When combined with other transgenic tools, they are now empowering rat researchers across the globe to address gene-centered hypotheses in widely studied physiological, pharmacological, biochemical, and behavioral model systems.

Guerts is a key contributor to this exciting technology development and was responsible for the world’s first targeted gene knockout rats. For  a more thorough description, you can read about the Knockout Rats in a Science article from 2009.

Maria Henningsen, CERG