epigenetics introductory collection

To understand what epigenetics is, we need to understand what genes are and why determine who and what we are. Luckily when I started to dive into this topic, I found this wonderful BBC documentary that is worth watching every minute.

 

In the video, the story of Överkalix caught my interest and I simply had to research deeper into this topic. Let’s re-collect what we just learned in the video:

Marcus Pembrey (a Professor of Clinical Genetics at the Institute of Child Health in London) and Swedish researcher Lars Olov Bygren found evidence in the historical records of Överkalix that an environmental effect is being passed down the generations. They have shown that a famine at critical times in the lives of the grandparents can affect the life expectancy of the grandchildren. This is the first evidence that an environmental effect can be inherited in humans. It also shows that the “memory” of this impact doesn’t necessarily have to affect the next generation but can even effect the grand-children generation.

There’s more detailed information in the article here:

http://io9.com/how-an-1836-famine-altered-the-genes-of-children-born-d-1200001177

Among the 1905 birth cohort, those who were grandsons of Överkalix boys who had experienced a “feast” season when they were just pre-puberty—a time when sperm cells are maturing—died on average six years earlier than the grandsons of Överkalix boys who had been exposed to a famine season during the same pre-puberty window, and often of diabetes.

When a statistical model controlled for socioeconomic factors, the difference in lifespan became 32 years, all dependent simply on whether a boy’s grandfather had experienced one single season of starvation or gluttony just before puberty. It appeared that Överkalix grandfathers were somehow passing down brief but important childhood experiences to their grandsons.

Interestingly, there’s also some more evidence from Quebec’s Ice Storm in 1998:

http://www.sciencedaily.com/releases/2014/09/140929105358.htm
The number of days an expectant mother was deprived of electricity during Quebec’s Ice Storm predicts the epigenetic profile of her child, a new study finds.

Thirteen years after the storm, DNA within the T cells — a type of immune system cell — of 36 children showed distinctive patterns in DNA methylation. T cells are a type of lymphocyte (itself a type of white blood cell) that play a central role in cell-mediated immunity.
The objective stress exposure (such as days without electricity) and not the degree of emotional distress in pregnant women that causes long lasting changes in the epigenome of their babies.

So let’s try to understand what methylation is:

http://en.wikipedia.org/wiki/DNA_methylation

DNA methylation is a biochemical process where a methyl group is added to the cytosine or adenine DNA nucleotides. DNA methylation may stably alter the expression of genes in cells as cells divide and differentiate from embryonic stem cells into specific tissues. The resulting change is normally permanent and unidirectional, preventing a cell from reverting to a stem cell or converting into a different cell type. DNA methylation is typically removed during zygote formation and re-established through successive cell divisions during development. Some methylation modifications that regulate gene expression are heritable and cause genomic imprinting.

If you want to dig deeper into the methylation, here is another video:

 

https://en.wikipedia.org/wiki/Genomic_imprinting

Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. It is an epigenetic phenomenon by which certain genes can be expressed in a parent-of-origin-specific manner.

Most multicellular organisms have two sets of chromosomes; that is, they are diploid. Each autosomal gene is therefore represented by two copies, or alleles, with one copy inherited from each parent. An allele is one of a number of alternative forms of the same gene or same genetic locus. Most such genetic variations result in little or no observable variation. For the vast majority of autosomal genes, expression occurs from both alleles simultaneously.
In mammals, however, a small proportion (<1%) of genes are imprinted, meaning that gene expression occurs from only one allele. The expressed allele is dependent upon its parental origin. In the mouse for example, the gene encoding Insulin-like growth factor 2 (IGF2/Igf2) is only expressed from the allele inherited from the father.

It is a dynamic process because imprints can be erased and re-established through each generation. Thus, genes that are imprinted in an adult can still be expressed in that adult’s offspring. For example, the maternal genes that control insulin production will be imprinted in a male but will be expressed in any of the male’s offspring that inherit these genes. The nature of imprinting must therefore be epigenetic rather than DNA sequence dependent.

DeChiara et al (1991) studied mice that carry a targeted disruption of the gene encoding insulin-like growth factor II (IGF-II). Transmission of this mutation through the male germline results in heterozygous progeny that are growth deficient. In contrast, when the disrupted gene is transmitted maternally, the heterozygous offspring are phenotypically normal.

https://en.wikipedia.org/wiki/Allele

An allele is one of a number of alternative forms of the same gene or same genetic locus. Most such genetic variations result in little or no observable variation.

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