[Journal Article] Novel Genetic Patterns May Make Us Rethink Biology and Individuality

From the 7 November 2013 ScienceDaily article

Professor of Genetics Scott Williams, PhD, of the Institute for Quantitative Biomedical Sciences (iQBS) at Dartmouth’s Geisel School of Medicine, has made two novel discoveries: first, a person can have several DNA mutations in parts of their body, with their original DNA in the rest — resulting in several different genotypes in one individual — and second, some of the same genetic mutations occur in unrelated people. We think of each person’s DNA as unique, so if an individual can have more than one genotype, this may alter our very concept of what it means to be a human, and impact how we think about using forensic or criminal DNA analysis, paternity testing, prenatal testing, or genetic screening for breast cancer risk, for example. Williams’ surprising results indicate that genetic mutations do not always happen purely at random, as scientists have previously thought.

His work, done in collaboration with Professor of Genetics Jason Moore, PhD, and colleagues at Vanderbilt University, was published in PLOS Genetics journal on November 7, 2013.

Genetic mutations can occur in the cells that are passed on from parent to child and may cause birth defects. Other genetic mutations occur after an egg is fertilized, throughout childhood or adult life, after people are exposed to sunlight, radiation, carcinogenic chemicals, viruses, or other items that can damage DNA. These later or “somatic” mutations do not affect sperm or egg cells, so they are not inherited from parents or passed down to children. Somatic mutations can cause cancer or other diseases, but do not always do so. However, if the mutated cell continues to divide, the person can develop tissue, or a part thereof, with a different DNA sequence from the rest of his or her body.

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f our human DNA changes, or mutates, in patterns, rather than randomly; if such mutations “match” among unrelated people; or if genetic changes happen only in part of the body of one individual, what does this mean for our understanding of what it means to be human? How may it impact our medical care, cancer screening, or treatment of disease? We don’t yet know, but ongoing research may help reveal the answers.

Christopher Amos, PhD, Director of the Center for Genomic Medicine and Associate Director for Population Sciences at the Cancer Center, says, “This paper identifies mutations that develop in multiple tissues, and provides novel insights that are relevant to aging. Mutations are noticed in several tissues in common across individuals, and the aging process is the most likely contributor. The theory would be that selected mutations confer a selective advantage to mitochondria, and these accumulate as we age.” Amos, who is also a Professor of Community and Family Medicine at Geisel, says, “To confirm whether aging is to blame, we would need to study tissues from multiple individuals at different ages.” Williams concurs, saying, “Clearly these do accumulate with age, but how and why is unknown — and needs to be determined.”

…

Just as our bodies’ immune systems have evolved to fight disease, interestingly, they can also stave off the effects of some genetic mutations. Williams states that, “Most genetic changes don’t cause disease, and if they did, we’d be in big trouble. Fortunately, it appears our systems filter a lot of that out.”

Mark Israel, MD, Director of Norris Cotton Cancer Center and Professor of Pediatrics and Genetics at Geisel, says, “The fact that somatic mutation occurs in mitochondrial DNA apparently non-randomly provides a new working hypothesis for the rest of the genome. If this non-randomness is general, it may affect cancer risks in ways we could not have previously predicted. This can have real impact in understanding and changing disease susceptibility.”

 

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Mayo Clinic plans to sequence patients’ genomes to personalise care

 

Image via Wikipedia

Mayo Clinic plans to sequence patients’ genomes to personalise care [The Guardian]

Project will give doctors the genetic information they need to choose drugs that work best and minimise side effects

Excerpt from the 27 December article

Doctors have drawn up plans to sequence the full genetic code of thousands of people in a landmark project to personalise their medical care.

Volunteers will have all six billion letters of their genome read, stored and linked to their medical records to help doctors prescribe more effective drugs and other therapies.

The prestigious Mayo Clinic in the US will launch the pilot study early next year as part of an ambitious move towards an era of “proactive genomics” that puts modern genetics at the centre of patient care.

The trial reflects a growing trend in medicine to use genetic information to identify those patients who will benefit most from a drug and those who will respond better to an alternative.

Other medical centres around the world that are thinking of introducing their own whole genome tests will be watching the trial with interest.

The wealth of information locked up in the human genome can help doctors advise patients on lifestyle changes to stave off diseases they are at risk of developing, but in many cases that advice is familiar and generic – for example focusing on healthy eating, regular exercise, drinking in moderation and not smoking.

The Mayo Clinic trial goes further by giving doctors all the genetic information they need to choose drugs that will work best for a particular patient while minimising side effects.

 Read the entire article

 

 

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How many genomes do you have? | SmartPlanet

How many genomes do you have? | SmartPlanet.

By John Rennie | November 29, 2011, 3:00 AM PST

The era of personal genomics is fast approaching, as headlines constantly remind us. With the cost of sequencing someone’s DNA rapidly falling toward just $1,000 (or less), it seems all but inevitable that soon we and our physicians will use that information to guide our health decisions.

 

 

454 Life Sciences gene sequencing machines. (Credit: Jon Callas, via Flickr)

 

But here’s an inconvenient biological truth that the triumphant talk about personal genomics sometimes skirts: we don’t each have just one genome. Yes, one may stand out most prominently for each of us, but we have others. And biology is still sorting out how much our health may depend on learning to pay attention to those we normally overlook.

 

All the cells in an organism like a human being certainly seem as though they should have the same genome. A fertilized egg divides repeatedly to give rise to the body’s cells, passing along the same set of chromosomes to every one of its cellular progeny. A few exceptional tissues might deviate from that rule — for example, red blood cells entirely discard the nucleus holding their genes, and the white blood cells called B lymphocytes scramble part of their DNA so that they can make an almost infinite number of different antibodies. But fundamentally, all the cells in the skin, the liver, the brain, the muscles and other tissues ought to share the same genome.

Or so it was thought. Yet exceptions to the rule keep cropping up, and they may help to explain some of the variation seen in tissues like the brain.

Variation on the brain

The hundred billion neurons in the human brain obviously differ from one another in their interconnections and in the specific neurochemical messenger molecules that they secrete. But a more subtle difference that has come to light over the past decade, largely thanks to the work of Michael J. McConnell and his colleagues at the Salk Institute for Biological Studies in La Jolla, Calif., resides in the DNA. They have shown extensive variation in the genomes of individual neurons, a condition called aneuploidy. The neurons have deleted, duplicated, and rearranged portions of their chromosomes, such that no two have exactly the same DNA sequence anymore…..

 

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Environment And Diet Leave Their Prints On The Heart

From the 30 November 2011 Medical News Today article 

A University of Cambridge study, which set out to investigate DNA methylation in the human heart and the ‘missing link’ between our lifestyle and our health, has now mapped the link in detail across the entire human genome.

The new data collected greatly benefits a field that is still in its scientific infancy and is a significant leap ahead of where the researchers were, even 18 months ago.

Researcher Roger Foo explains: “By going wider and scanning the genome in greater detail this time – we now have a clear picture of the ‘fingerprint’ of the missing link, where and how epigenetics in heart failuremay be changed and the parts of the genome where diet or environment or other external factors may affect outcomes.” …

…

DNA methylation leaves indicators, or “marks”, on the genome and there is evidence that these “marks” are strongly influenced by external factors such as the environment and diet. The researchers have found that this process is different in diseased and normal hearts. Linking all these things together suggest this may be the “missing link” between environmental factors and heart failure.

The findings deepen our understanding of the genetic changes that can lead to heart diseaseand how these can be influenced by our diet and our environment. The findings can potentially open new ways of identifying, managing and treating heart disease.

The DNA that makes up our genes is made up of four “bases” or nucleotides – cytosine, guanine, adenine and thymie, often abbreviated to C, G, A and T. DNA methylation is the addition of a methyl group (CH3) to cytosine.

When added to cytosine, the methyl group looks different and is recognised differently by proteins, altering how the gene is expressed i.e. turned on or off.

DNA methylation is a crucial part of normal development, allowing different cells to become different tissues despite having the same genes. As well as happening during development, DNA methylation continues throughout our lives in a response to environmental and dietary changes which can lead to disease.

As a result of the study, Foo likens DNA methylation to a fifth nucleotide: “We often think of DNA as being composed of four nucleotides. Now, we are beginning to think there is a fifth – the methylated C.”

Foo also alludes to what the future holds for the study: “…and more recent basic studies now show us that our genome has even got 6th, 7th and 8th nucleotides… in the form of further modifications of cytosines. These are hydroxy-methyl-Cytosine, formylCytosine and carboxylCytosine = hmC, fC and caC! These make up an amazing shift in the paradigm…”

As in most studies, as one question is resolved, another series of mysteries form in its place. The study shows that we are still on the frontier of Epigenetics and only just beginning to understand the link between the life we lead and the body we have. 

DNA methylation in E.coli

Related articles

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