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View Poll Results: Have you participated in an Epigenetic study?
Have you participated in an Epigenetic study? 0 0%
Have you participated ina Cancer Genome study? 0 0%
Have you had genetic testing for BRCA1, BRCA & BART? 2 66.67%
Have you had genetic testing for TOP2A, KRAS, etc 1 33.33%
Multiple Choice Poll. Voters: 3. You may not vote on this poll

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Old 03-19-2014, 03:33 PM   #1
'lizbeth
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Post Epigenetics

A chapter from 100 Most important Science Ideas by Mark Henderson Joanne Baker and Tony Crilly

Epigenetics

It was previously thought that a person’s genetic makeup is arrived at independently of any environmental influences, but it now appears that sometimes acquired characteristics may, in fact, be passed on in the genes to succeeding generations.

In the autumn of 1944, railway workers in the Netherlands, then under German occupation, went on strike to assist the advancing Allies. When the initial British and American assault failed, the Nazis retaliated by imposing a devastating food embargo. At least 20,000 Dutch citizens starved or died of malnutrition in the ensuing famine.
The effects of the Hongerwinter or “Hunger Winter” were to last long beyond the country’s liberation in 1945. Mothers who were pregnant during the famine had clidren with an elevated risk of a wide range of health problems, including diabetes, obesity and cardiovascular disease. In some cases, even their grandchildren were more likely to be born underweight. While damage to the first generation’s health might be explained by malnutrition during pregnancy, the Netherlands was a rich nation by the time the second generation was born. Yet, an inherited effect remained.

The story of the Dutch famine is not unique. The village of Överkalix, in northern Sweden, boats meticulous historical records of harvests, births and deaths, which have allowed Marcus Pembrey, of the Institute of Child Health in London, to conduct and exhaustive study of food availability and life expectancy. He found that when boys grew up during periods of plenty, their grandsons were more likely to die at a young age. Further analysis revealed that this reflected a predisposition only through the male line.

Both examples suggest that people’s health can be affected by the diets followed by their grandparents. Yet according to orthodox evolutionary theory, such an effect should be impossible. Acquired characteristics are not supposed to be inherited – that was the Lamarckian heresy, which has not been fashionable since Darwin.

“We are changing the view of what inheritance is. You can’t, in life, in ordinary development and living, separate out the gene from the environmental effect. They’re so intertwined.” Marcus Pembrey


Genetic memory

The Dutch and Swedish experiences can be explained by a phenomenon know as epigenetics, by which the genome appears to “remember” certain environmental influences to which it has been exposed. Normally, these epigenetic effects act only on the somatic cells of the adult body, switching genes off or otherwise adjusting their activity. Some, however, can also alter sperm and eggs, to be inherited by future generations. Acquired characteristics, it turns out, can sometime be passed on after all.

Epigenetics owes its prefix to the ancient Greek for “over” or “on,” and it generally relies on two broad mechanisms. One is methylation and the process we met in Chapter 20, which silences genes by adding part of a molecule called a methyl group to the DNA base cyosine, or C. The other is modification of chromatin, the combination of DNA and histones (kinds of protein), of which chromosomes are made up. Changes to chromatin structure can affect which genes are made available for transcription into messenger RNA and protein, and which are hidden away out of reach. In neither case is the actual sequence of DNA altered at all, but changes in its organization can still be passed on from one cell to its offspring.

These epigenetic process are central to normal growth, development and metabolism. Every cell contains the full set of instructions that are needed by every type of tissue, and epigenetics determines which of these are actually issued and executed. It ensures that genes act in the body in response to environmental cues. Experiments with mice have demonstrated the lucidly: changes in diet while females are pregnant affect the coat color of their offspring, by modifying the way genes are methylated. This effect, indeed, could account for the surprising observation that many cloned animals differ from their parents in color and markings. While their genomes are identical, their “epigenomes” are not.

Normally, such epigenetic changes are stripped away from the genome during embryonic development, so that they are not passed on to offspring. But they can sometimes be retained, causing environmental effects on health and behavior that cascade down the generations. That could account for what happened in Holland and Sweden/ Prenatal diets seem to have changed the epigenetic programming of their children and grandchildren, to modify metabolism to cope with the prevailing nutritional environment. This, in turn, has influenced health risks such as diabetes.

The importance of the epigenome

As with copy number variation and junk DNA, science is starting to understand that epigenetic effects are just as significant to biology as convention genetic mutations. Epigenetics, for example, plays an important role in cancer. Several chemicals are known to be carcinogenic, even though they are not mutagens that directly damage DNA. They induce epigenetic effects, silencing important tumor suppressor genes, or altering chromatin structure so that oncogenes become more active.

Epigenetic markings also ensure that when cancer cells divide, their daughter cells are cancerous too. An understanding of how these processes work could open a new approach to medicine. The first cancer drug that works by removing methylation, Vidaza, was approved by the U.S. Food and Drug Administration in 2004.

The Human Epigenome Project, recently started by a European consortium, should help to bring more epigenetic therapies into medicine. This ambitious initiative aims to map all the possible methylation patterns of every gene in every type of human tissue. A pilot project has already achieved this for the major histo-compatibility complex – a cluster of genes on chromosome 6 that affect immune response.

Once these methylation sites have been identified, it should be possible to link variation to diseases, in much the same way as can be done for SNPs. Doctors, indeed, may well find their patients’ epigenomes more useful than their genomes. The genetic code, as the early history of gene therapy has proved, is painfully difficult to correct in living organisms; methylation should be comparatively simple to undo. Many of the medicines of the future could be designed to exploit this natural method of genetic control to treat and prevent disease.
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Old 03-19-2014, 03:49 PM   #2
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Re: Epigenetics

From Chapter 20 re: Methylation

Imprinted Genes
The genetic disease that a child with a 15q11 defect will get depends on which parent supplied the mutated chromosome. If it came back from the mother, it will be Angelman syndrome, and if it came from the father, it will be Prader-Willi. The gene that underlies these disorders is imprinted -- that is, carries a biological marker that tells cells to express only the maternal or paternal copy. Imprinted genes can "remember" their parental history, through a process known as methylation that leaves some switched on and others switched off.

Methylation

Imprinting works because of a process called DNA methylation by which the function of geners is altered by chemical modifications. It involves the addition of a chemical tag, know as a "methyl group", to the DNA base cytosine. This can turn down a gene's activity, or switch it off entirely. It is critical to ensuring that genes are expressed only at the right times in an organism's life cycle, and in the right kinds of tissue.

Most of these methyl tags are wiped away during the early stages of embryonic development. The main exceptions are the imprinted genes, which retain these marks to flag up their maternal or paternal origin.

Last edited by 'lizbeth; 03-19-2014 at 03:51 PM.. Reason: addition
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Old 03-19-2014, 08:00 PM   #3
StephN
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Re: Epigenetics

Can you add "None of the above" or are you not wanting to count those?
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MY STORY SO FAR ~~~~
Found suspicious lump 9/2000
Lumpectomy, then node dissection and port placement
Stage IIB, 8 pos nodes of 18, Grade 3, ER & PR -
Adriamycin 12 weekly, taxotere 4 rounds
36 rads - very little burning
3 mos after rads liver full of tumors, Stage IV Jan 2002, one spot on sternum
Weekly Taxol, Navelbine, Herceptin for 27 rounds to NED!
2003 & 2004 no active disease - 3 weekly Herceptin + Zometa
Jan 2005 two mets to brain - Gamma Knife on Jan 18
All clear until treated cerebellum spot showing activity on Jan 2006 brain MRI & brain PET
Brain surgery on Feb 9, 2006 - no cancer, 100% radiation necrosis - tumor was still dying
Continue as NED while on Herceptin & quarterly Zometa
Fall-2006 - off Zometa - watching one small brain spot (scar?)
2007 - spot/scar in brain stable - finished anticoagulation therapy for clot along my port-a-catheter - 3 angioplasties to unblock vena cava
2008 - Brain and body still NED! Port removed and scans in Dec.
Dec 2008 - stop Herceptin - Vaccine Trial at U of W begun in Oct. of 2011
STILL NED everywhere in Feb 2014 - on wing & prayer
7/14 - Started twice yearly Zometa for my bones
Jan. 2015 checkup still shows NED
2015 Neuropathy in feet - otherwise all OK - still NED.
Same news for 2016 and all of 2017.
Nov of 2017 - had small skin cancer removed from my face. Will have Zometa end of Jan. 2018.
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Old 03-20-2014, 08:38 AM   #4
'lizbeth
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Re: Epigenetics

Can I add more questions? - I stumbled upon the poll function and was just trying it out for the first time.
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