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Thursday, December 16, 2021

Epigenetics: Beyond DNA



Do life experiences modify our genetic inheritance to circumvent our genetic “fate”? 


“Epigenetics is the cellular equivalent of how to locate and place bookmarks.” — Ross L. Levine, physician and scientist


Everyone seems to be talking about epigenetics. That can be embarrassing when you may not be quite sure what it means or how it affects us. So, here’s a primer that can get you cocktail-party ready since we are finally gathering again for social functions.

The word “epigenetic” is literally translated to “above the genes.” It is changes that occur to genes outside of the DNA sequence. Epigenetics can account for what happens to us environmentally, such as after toxic exposure or resulting from nutritional differences. It can also account for differences that are impossible to explain otherwise, such as when one identical twin loves the outdoors and the other is a couch potato. Some epigenetic changes occur when we are developing in the womb.

Giving Away Genetic Information

Genetic testing company 23andme has biological information from millions of customers gathered over the past 14 years. In 2018 the company announced a deal with pharma giant GlaxoSmithKline to use the data (aggregated and anonymized) to develop pharmaceutical drugs. But what else is at stake? Ethical, privacy and security questions remain. Listen here for a rundown of the questions facing genetic testing companies.

“You had all these cases where things were clearly identical, genetically, but behaving differently,” says Mary Goll, a developmental biologist who studies epigenetics in zebrafish. “This suggested that there had to be something chromosomal and not related to the DNA sequence that was mediating that behavior.” Epigenetics has now been linked to conditions as disparate as autism and cancer.

How Do Changes Happen?

DNA is spooled around proteins and touched by other chemicals. This packaging, called chromatin, can influence whether genes are turned on or off. Three systems can interact to silence, or turn off, genes: DNA methylation, histone modifications, and RNA-associated silencing. That’s as deep as we’ll get here. The important thing to understand is that the way DNA is expressed is affected by factors that turn portions of it on or off.


                                                                                                                             Source: genome.gov 


Epigenetic changes are a part of normal development. For example, all of our cells have the same DNA, but there are a wide variety of cells with different functions: liver cells, neurons, inflammatory cells, and many more. Cells, tissue, and organs are different because certain sets of genes within them are expressed, or turned on, and others are silenced, or turned off. Your epigenetic state is different throughout your life, as DNA methylation increases with age. 

Some epigenetic changes are permanent, while others are not. An example is DNA methylation in smokers. Portions of the AHRR gene are less methylated in smokers than non-smokers, with the greatest difference being in heavy, long-term smokers. But DNA methylation increases in former smokers and can, over time, reach levels associated with non-smokers. 

Health

Germs can weaken your immune system via epigenetic changes, helping them to survive. An example of this is the tuberculosis bacterium, which can induce changes in histones to turn off the IL-12B gene.

Some epigenetic changes increase the risk of cancer, such as increased DNA methylation that results in a decreased BRCA1 expression, upping the risk of breast and other cancers. Methylation patterns can be used to identify certain cancers and find hard-to-detect cancers at an earlier stage. 

Nutrition during pregnancy can affect fetal health via epigenetics. Mothers who were pregnant during the Dutch hunger winter famine of 1944-45 gave birth to babies who were more prone to heart disease, schizophrenia, and type 2 diabetes compared to their siblings. Sixty years after the famine, researchers could still identify areas of increased and decreased methylation in the famine subjects that was in contrast to their brothers and sisters.

Finding Your People 

There are plenty of sites where you can submit a saliva test and some greenbacks in order to discover lost and distant relatives, and perhaps delve into family biology: 

23andme.com is a major player in the space, but see cautions in the sidebar.

Geneticgenie.org allows you to analyze your genome.

Livewello.com can process reports based on analysis of raw genetic files generated by 23andme, AncestryDNA and Family Tree DNA, or it can gather its own data to generate variance and health reports using single nucleotide polymorphisms.

MTHFR.net includes resources for the MTHFR gene, the mutation of which is believed to be the source of many health problems.

Hopefully now you’re at least able to pop in with an intelligent comment at the next Zoom call or water cooler gathering when someone brings up epigenetics. Check out the sources below if you want to dig in further or seek out a continued learning class on the subject. Healthcare is transforming rapidly, and this is one field that’s sure to have a major impact.