1.

Summarize the article (short

paragraph)
2. List all evidence based claims
3. List evidence of bias/opinion
4. List any counterclaims (where
scientist have different opinions about a
matter)
5. There are five text dependent
questions at the end of this article, make
sure to answer them.

Epigenetics and Inheritance

We used to think that a new embryo's epigenome was completely erased and rebuilt from
scratch. But this isn't completely true. Some epigenetic tags remain in place as genetic
information passes from generation to generation, a process called epigenetic inheritance.

Epigenetic inheritance is an unconventional finding. It goes against the idea that inheritance
happens only through the DNA code that passes from parent to offspring. It means that a parent's
experiences, in the form of epigenetic tags, can be passed down to future generations.

As unconventional as it may be, there is little doubt that epigenetic inheritance is real. In fact, it
explains some strange patterns of inheritance geneticists have been puzzling over for decades.
Overcoming the Reprogramming Barrier
Most complex organisms develop from specialized reproductive cells (eggs and sperm in
animals). Two reproductive cells meet, then they grow and divide to form every type of cell in
the adult organism. In order for this process to occur, the epigenome must be erased through a
process called "reprogramming."

Reprogramming is important because eggs and sperm develop from specialized cells with stable
gene expression profiles. In other words, their genetic information is marked with epigenetic
tags. Before the new organism can grow into a healthy embryo, the epigenetic tags must be
erased.

At certain times during development (the timing varies among species), specialized cellular
machinery scours the genome and erases its epigenetic tags in order to return the cells to a
genetic "blank slate." Yet, for a small minority of genes, epigenetic tags make it through this
process and pass unchanged from parent to offspring.
Reprogramming resets the epigenome of the early embryo so that it can form every type of cell
in the body. In order to pass to the next generation, epigenetic tags must avoid being erased
during reprogramming.

Bypassing Reproductive Cells

Epigenetic marks can pass from parent to offspring in a way that completely bypasses egg or
sperm, thus avoiding the epigenetic purging that happens during early development.

Most of us were taught that our traits are hard-coded in the DNA that passes from parent to
offspring. Emerging information about epigenetics may lead us to a new understanding of just
what inheritance is.

Nurturing behavior in rats

Rat pups who receive high or low nurturing from their mothers develop epigenetic differences
that affect their response to stress later in life. When the female pups become mothers
themselves, the ones that received high quality care become high nurturing mothers. And the
ones that received low quality care become low nurturing mothers. The nurturing behavior itself
transmits epigenetic information onto the pups' DNA, without passing through egg or sperm.

TRY YOUR HAND AT BEING A RAT MOTHER: LICK YOUR RATS!

Gestational diabetes
Mammals can experience a hormone-triggered type of diabetes during pregnancy, known as
gestational diabetes. When the mother has gestational diabetes, the developing fetus is exposed
to high levels of the sugar glucose. High glucose levels trigger epigenetic changes in the
daughter's DNA, increasing the likelihood that she will develop gestational diabetes herself.

In mammals, about 1% of genes escape epigenetic reprogramming through a process called

Imprinting.

LEARN MORE: IMPRINTING

The Challenges of Proving Epigenetic Inheritance
Proving epigenetic inheritance is not always straightforward. To provide a watertight case for
epigenetic inheritance, researchers must:

 Rule out the possibility of genetic changes

In organisms with larger genomes, a single mutation can hide like a needle in a haystack.

 Show that the epigenetic effect can pass through enough generations to rule out the
possibility of direct exposure
In a pregnant mother, three generations are directly exposed to the same environmental
conditions at the same time. An epigenetic effect that continues into the 4th generation
could be inherited and not due to direct exposure.

Researchers face the added challenge that epigenetic changes are transient by nature. That is, the
epigenome changes more rapidly than the relatively fixed DNA code. An epigenetic change that
was triggered by environmental conditions may be reversed when environmental conditions
change again.
Three generations at once are exposed to the same environmental conditions (diet, toxins,
hormones, etc.). In order to provide a convincing case for epigenetic inheritance, an epigenetic
change must be observed in the 4th generation.

Implications for Evolution

Epigenetic inheritance adds another dimension to the modern picture of evolution. The genome
changes slowly, through the processes of random mutation and natural selection. It takes many
generations for a genetic trait to become common in a population. The epigenome, on the other
hand, can change rapidly in response to signals from the environment. And epigenetic changes
can happen in many individuals at once. Through epigenetic inheritance, some of the experiences
of the parents may pass to future generations. At the same time, the epigenome remains flexible
as environmental conditions continue to change. Epigenetic inheritance may allow an organism
to continually adjust its gene expression to fit its environment - without changing its DNA code.

References
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Treating Genetic Disorders
Duchenne Muscular Dystrophy (DMD)is a genetic disorder that is caused by a gene located on
the X chromosome. It affects about 1 in 3,600 boys. The reason it affects boys more than girls is
because of the way sex chromosomes are inherited. Females receive two X chromosomes, they
only need to have one working copy of the gene, so even if they carry the DMD gene, they will
have a working copy on the other chromosome. Males have an X chromsome and a Y
chromosome. If a boy inherits the DMD allele from his mother, he will not have another normal
allele and will express the muscular dystrophy trait.

Symptoms usually appear in childhood, though a child can be tested for the trait at birth. Over
time, muscle weakness affects the body, usually starting at the legs. Children will eventually lose
the ability to walk by the age of twelve. Death usually occurs by the time the person has reached
25 years of age.

The actual cause of the muscle degeneration is due to the protein dystrophin. This protein
connects muscle fibers to underlying tissue and insulates the muscle from damage. Lack of this
protein results in muscle cell death, where those cells are replaced with fat or connective tissue.
Recall that genes on chromosomes code for amino acids, which in turn build proteins. An error
in the genetic code can result in a protein not being made correctly, or not made at all. While a
person can inherit a faulty gene from their mothers, it is also possible for this section of DNA to
have a spontaneous mutation, which can also result in the disorder.

In order to treat the disorder, you would either need to artificially make the protein required for
insulating muscle cells, or repair the gene that makes the protein. There are several mutations
that can result in muscular dystrophy, but a common one results from the deletion of a section of
DNA, which then causes a frameshift mutation, making the gene unreadable by cellular
machinary. Recall that during the processof transcription, DNA makes RNA, which travels to the
ribosomes where the amino acids are assembled into a protein. Each 3 bases in the RNA
sequence codes for an amino acid. If one of those bases are removed the whole reading frame
shifts the protein cannot be made. Imagine if you read words 3 letters at a time....what would
result in your reading if one of the letters were deleted?

THE|CAT|ATE|THE|RAT

If the first E were deleted, the words (and meaning) would change to:

THC|ATA|TET|HER|AT

This is sometimes called a nonsense mutation.

One promising technology uses a drug to cause the machinery of the cell to skip the deleted
portion, so that the protein created is a shorter version of dystrophin, but still functions to protect
the muscle cells from damage. If you use the same analogy as above, the reading frame would
say

THE|CAT|ATE|RAT

While it's not perfect, it is no longer complete nonsense.

How Eteplirson Works

 

The drug may not work on all patients, as it depends greatly on the mutation of the gene. The
dystrophin gene is one of the largest human genes, containing 79 exons. An exon is a portion of
the gene that actually codes for the protein, sections that are interspersed with introns, or non-
coding segments. Clinical trials of drugs that allow for exon skipping have shown promise in
treating the disease. However, the drug will only work if the person has not already had muscle
function severely compromised. The drug may protect damage to muscles, but it will not repair
muscles that have already been damaged by the progression of the disease. Clinical trials are
limit participants to those who are still able to walk.

 
 Analysis (Close Reading Exercise)

1. Summarize the article in 140 characters or less (TWEET). Summarize it in such a way that it
might inspire your followers to read it.

2. Images are difficult for those who have visual impairments. Choose one of the images in the
article and describe the content to a person who may have trouble viewing it.

3. There are several vocabulary words related to genetics and molecular biology. From the
article, locate and circle at least three of these technical terms. Suggest a definition or description
for each.

4. Suggest a reason why eteplirsen would not work for all DMD patients. Use scientific language
in your answer.

5. Write two questions you have that relate to the content of the article. These questions would
be ways the author could extend the article or provide more details with that is already included.

Publisher: Biologycorner.com; follow on Google+

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0
Unported License.

Resources:

http://www.today.com/health/moms-heartache-two-sons-have-deadly-disease-only-one-can-
6C10077829
http://www.thestreet.com/story/11906821/1/a-dmd-expert-and-mother-calls-for-eteplirsens-
rapid-approval.html

http://www.muscular-dystrophy.org/about_muscular_dystrophy/research_faqs/
612_what_is_exon_skipping_and_how_does_it_work

Related Lab: Detecting Genetic Disorders - use electrophoresis to idenfify carriers within a
family
Related Worksheet: X-Linked Genetic Problems