BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: methylation

CRISPR/Cas9 System undoing genetic disease? Maybe!

A recent study released from the Whitehead Institute for Biomedical Research discuss the pioneering way scientists are using CRISPR technology to help boys born with Fragile X syndrome.

Fragile X syndrome is a rare condition affecting 1 out of 3600 boys born. Symptoms of this genetic condition are delayed development, often impulsive actions and intellectual difficulties. There is no cure. The disease is caused by DNA methylation, which is caused by the random addition of a methyl (CH3) group to the DNA strand. CRISPR technology has made it possible for this methylation to be removed – essentially, the CRISPR/Cas9 system removes the extra CH3 group.

Source: https://commons.wikimedia.org/wiki/File:DNA_methylation.svg

The mutation occurs in the FMR1 gene on the X chromosome, as the name suggests. The methylation prevents the expression of the FMR1 gene, and the CRISPR/Cas9 system removes the added CH3 group, allowing the gene to be expressed. The FMR1 gene is crucial in brain and cognitive development, so the CRISPR technology allows for this gene to function – virtually rescuing the person from the disease.

Due to the successful application of CRISPR technology to Fragile X syndrome and the FMR1 gene, this rare disease is better understood by scientists. This same technology, which removes the added CH3 group, thus removing the methylation, is hypothesized to be useful in lessening or eliminating symptoms from diseases such as muscular dystrophy.

Epigenetics for Asthmatics


In a recent study, a group of scientists obtained findings that could lead to a new approach to treating allergies. Instead of looking at the genes of their test subjects, they looked at something “above” the genome. Here we reach the field of Epigenetics.
Let us first define “Epigenetics” as the study on the activity and regulation of genes. In the world of Epigenetics, one can think of the epigenome as the on-off switch for the expression of genes. In terms of the study lead by Professors William Cookson and Miriam Moffatt, they focus on genes that trigger Asthma in patients. As Asthma cannot be ‘cured’, is there a way to shut down the genes that cause it?

The research team searched for a correlation between Asthma-causing antibodies and low methylation levels. Methylation is the process by which a methyl group attaches to certain genes in order to regulate their activity. Scientists already know that people with asthma have higher levels of an antibody called “Immunoglobin E” (IgE). This antibody is involved in triggering the symptoms of asthma. It is already known that genes responsible for producing IgE are hyperactive in asthma patients. The question became whether methylation had something to do with it. So to answer this question, the researchers obtained volunteers with asthma, but with varying IgE levels. The group found significant results surrounding lower levels of methylation with the patients that had higher levels of IgE than those with lower levels of IgE in their blood. This suggests that the lower methyl levels on certain genes evokes an overactivity of IgE producing genes.

After reading the article myself, I wonder if asthma patients could find ways to have higher methyl levels in their body to shut down the overactive IgE-producing genes. Perhaps they could consume a methyl rich diet? I guess it’s not that simple. Further research should obviously go into epigenetics, since I feel it is a newly discovered field. Anyways, here are the head scientists reactions to the experiments:

Professor Moffatt: “The genes we identified represent new potential drug targets for allergic diseases as well as biomarkers that may predict which patients will respond to existing expensive therapies.”

Professor Cookson: “Our pioneering approach, using epigenetics, allowed us to obtain insights that we weren’t able to get from traditional genetics. It isn’t just the genetic code that can influence disease and DNA sequencing can only take you so far. Our study shows that modifications on top of the DNA that control how genes are read may be even more important.”

This article (and the entire study of Epigenetics) shows how scientific knowledge and thought is always changing. Before recent research showing a link between one’s living environment and their genetic activity came along, scientists widely believed that one only passes down inherited genes to their offspring. This potentially makes scientists now look twice at Lamarck and Darwin’s theories of evolution. Due to the new research conducted on Epigenetics, Lamarck’s (originally rejected) theory of how an animal’s environment will affect that animal’s offspring can now be regarded in a whole new light.

Original Article: http://www.sciencedaily.com/releases/2015/02/150218073057.htm

Further Reading: http://www.extremetech.com/extreme/180963-lamarcks-revenge-the-epigenetics-revolution-may-redeem-one-of-darwins-oldest-rivals

Regular Exercise Can Change Our DNA

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Most people (hopefully) know that exercise and physical activity are beneficial to almost everyones physical and mental health. Exercising improves one’s mood, boosts energy, controls weight, helps the body fight against diseases, reduces stress, and many more life benefits. A new study  by a group of scientists in Sweden discovered how the influence of physical exercise actually has that beneficial effect on the human body.

The scientists focused their work on 23 young, healthy men and women at the Karolinska Institute in Stockholm. The participants were asked to exercise on stationary bikes for 45 minutes, four times per week, for three months. The scientists understood that it would be difficult to study the full changes on each person because they can’t isolate the other aspects of someone’s life like diet or other behaviors. Because of this issue, each person only exercised one leg so they essentially became their own control group.

After the three months had passed, the scientists clearly saw that the exercised leg was stronger. They also studied the DNA of the muscle cells and compared them between each leg. The genome of muscle cells on the exercised leg had new methylation patterns. DNA Methylation is the process of methyl groups attaching to the outside of a gene and making the gene more or less able to respond to biochemical signals. This entire study is also known as epigenetis. Epigenetics is the study of modifications of DNA influenced by the environment. The scientists found that exercise has a huge effect on human epigenetics based on methylation patterns.

The experiment showed that many of the methylation changes were on the enhancer part of the genome. Enhancers “bind to activator proteins which help connect transcription factors to RNA polymerase and the promotor region to turn on transcription of a gene” (from Mrs. Newitt notes packet). The enhancers amplified the expression of proteins by genes that effect energy, insulin, muscle inflammation and muscle pain.

Exercising is good for you and now we know why. It affects how healthy and fit our muscles become. The results of this study will now help lead other scientists into methylation pattern and gene expression research.

 

Main article:

http://well.blogs.nytimes.com/2014/12/17/how-exercise-changes-our-dna/?_r=0

Other articles of interest:

http://www.ncbi.nlm.nih.gov/pubmed/25484259

http://learningenglish.voanews.com/content/study-regular-exercise-can-change-our-dna/2580467.html

http://www.cell.com/cell-metabolism/abstract/S1550-4131(12)00005-8?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413112000058%3Fshowall%3Dtrue

http://www.mayoclinic.org/healthy-living/fitness/in-depth/exercise/art-20048389?pg=1

Does long-term endurance training impact muscle epigenetics?

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Epigenetics translates to “above” or “on top of” genetics. To be more specific, Epigenetics is the study of how modification of gene expression can cause changes in many organisms.

A new study from Karolinska Institutet in Sweden explores the theory that long-term endurance training alters the epigenetic pattern in the human skeletal muscle. The team that conducted the research also explored strong links between these altered epigenetic patterns and the activity in genes controlling improved metabolism and inflammation.

The study was conducted using 23 young and healthy men and women. The men and woman would perform one-legged cycling – where the untrained leg would be the control of the experiment. Four times a week and over the course of three months, the volunteers would participate in a 45 minute training session. Though skeletal muscle biopsies, supervisors would measure their markers for skeletal muscle metabolism, methylation status of 480,000 sites in the genome, and activity of over 20,000 genes.

At the end of the study, the researchers concluded that there was a strong relationship between epigenetic methylation and the change in activity of 4000 genes in total. Epigenetic methylation is defined as the “addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. ” Moreover, it was determined that methylation levels increased when involved in skeletal muscle adaptation and the metabolism of carbohydrates. However, methylation levels decreased in regions associated to inflammation.

Furthermore, Carl Johan Sundberg found that “endurance training in a coordinated fashion affects thousands of DNA methylation sites and genes associated to improvement in muscle function and health.” He believes that this determination could be vital to understanding the treatment of diabetes and cardiovascular disease as well as how to properly maintain good muscle function throughout life.

This article relates very much to our work in class as we learn the Molecular Genetics Unit. It connects because we are learning what happens when mutations occur in one’s genome and the impacts those mutations have on someone. For example, cancer is one of the most researched and explored topics in regard to how modification of gene expression alters organisms. Oncogenes and Tumor suppressor genes have vital impacts on cellular division, changes to cellular function, and the growth of tumors.

Diesel Exhaust Causes Changes Within

Diesel Exhaust

Two hours of exposure to diesel exhaust fumes has proven to show fundamental health-related changes in biology by switching some genes on and others off.

A study put volunteers in a polycarbonate-enclosed booth and had them breath diluted and aged exhaust fumes. These fumes were about equal to the air quality along a Beijing highway. The researchers examined how the exposure affected the chemical coating that attaches to many parts of a person’s DNA. The coating they were referring to is carbon-hydrogen coating, also known as methylation. The coating can silence or dampen a gene and prevent it from producing a protein. Methylation is a mechanism for controlling gene expression.

The study found that diesel exhaust caused changes in methylation located at about 2,800 different places along a person’s DNA, which affects about 400 genes. Some places led to more methylation. How these changes affect health is the next topic of research. However, the AstraZeneca Chair in Occupational and Environmental Lung Disease claims that the fact that DNA methylation was affected from only two hours of exposure is a positive implication; when something happens that quickly, it usually means you can reverse it through either therapy, change in environment, or change in diet.

This article is very similar to what we are learning about methylation and epigenetics. It discusses how the environment can affect someone’s genes and their gene expression as opposed to solely being their DNA sequence. I found this interesting because diesel exhaust is something people are exposed to everyday and it is important to know the affects it can have other than just respiratory issues.

Source:

http://www.eurekalert.org/pub_releases/2015-01/uobc-bid010715.php

http://aqicn.org/city/beijing/

http://www.whatisepigenetics.com/dna-methylation/

http://commons.wikimedia.org/wiki/File:Diesel-smoke.jpg

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