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Epigenetics :)

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Alex Belfi

on 25 November 2013

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Transcript of Epigenetics :)

Epigenetics
You are more than your DNA
Question #1: How do different adult stem cells know their fate?
Questions to Consider:
Question #2: How can identical twins have slightly different phenotypes?
Question #4: How can females express only one X chromosome per cell?
Question #5: How do your actions as a ten-year-old not only affected your genes, but those of your future children and grandchildren?
Variable Expressivity:
* Definition: The study of heritable changes in gene activity which are not caused by changes in the DNA sequence.
* Unlike simple genetics based on changes to the genome, the changes in gene expression or cellular phenotype of epigenetics have other, environmental, causes.
* Nature (genome) *via nurture (epigenome)
* The name epi- (Greek: over-, above-) -genetics.
University of Utah
DNA :)
* Myoblasts can only form muscle cells.
* Keratinocytes only form skin cells.
* Hematopoietic cells only become blood cells.
* But all have identical DNA sequences.
* Identical genotypes -> Identical genes -> Identical traits...right?
Question #3: How can identical twin litter mates show different coat colors at birth?
Created By: Alex Belfi
Question #1: How do different adult stem cells know their fate?
Question #2: How can identical twins have slightly different phenotypes?
Reduced/Incomplete Penetrance:
* Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder.
* If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance (often occurs with familial cancer syndromes).
* Probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown.
*This phenomenon can make it challenging for genetics professionals to interpret a person’s family medical history and predict the risk of passing a genetic condition to future generations.
* Although some genetic disorders exhibit little variation, most have signs and symptoms that differ among affected individuals.
* Variable expressivity refers to the range of signs and symptoms that can occur in different people with the same genetic condition.
* As with reduced penetrance, variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified.
* If a genetic condition has highly variable signs and symptoms, it may be challenging to diagnose.
* Discordance - The degree of dissimilarity in a pair of twins with respect to the presence or absence of a disease or trait.
* "Identical twins" replaced with "monozygotic" twins
* Incomplete Penetrance
Genetics vs. Epigenetics
FOR EXAMPLE:
* Somatic Mutation Theory (SMT) - Cancer is a case of evolution on a small scale.
* We can use cancer cells to generate normal cells by exposing them to stem cells.
* Cancer cells show an overall REDUCTION in methylation.
* Spontaneous remission of advanced cancers can occur (cancer can be normalized) through interactions with normal cells, whether in a stem cell environment or in that of fully differentiated cells.

* John Gurdon - Showed that specialized cells possess all the genetic information necessary to specify all other types of cells in an animal. (He was the first to clone an entire organism - frog).
* Specialized cells do not lose any genes while assuming their particular identity.
* iPS - Induced Pluripotent Stem Cells.
*Heritable changes: mutations in germ cells ARE inherited & epigenetic modifications can be passed to succeeding generations
*Complete Library: Genome
* Function: Codes for RNA and proteins
* Informational Format: DNA language (genes)
* Variation from cell type to cell type: None
* Changes by Lifestyle: Nope
*Complete Library: Epigenome
* Function: Controls DNA expression
* Informational Format: Methyl tags on C-bases & tagging of histone tails
* Variation from cell type to cell type: Much variation, 200+ cell types -> 200+ epigenomes
* Changes by Lifestyle: Definitely
Methylation:
* Methyl Tags - In mammals, it is chemically glued to the base C, creating "methylated cytosine."
* Methyltransferase - (methylase) An enzyme that directs the transfer of methyl groups to histones.
* Multiple methyl tags - dimethylated (2) & trimethylated (3).
Stem Cells & Cancer:
Mapping sequences with differential DNA methylation
between MZ twins:
* Acetyl Tags - Acts as the unlocking device of DNA.
* Attached by Histone Acetylace Enzyme (HAC).
* Removed from histone tails by Histone Deacetylase Enzyme (HDAC).
* Proteins, called transcription factors, open up certain selected DNA spools for usage in that particular cell.
Acetylation:
* Many people with a mutation in the BRCA1 or BRCA2 gene will develop cancer during their lifetime, but some people will not. Doctors cannot predict which people with these mutations will develop cancer or when the tumors will develop.

FOR EXAMPLE:
* The features of Marfan syndrome vary widely— some people have only mild symptoms (such as being tall and thin with long, slender fingers), while others also experience life-threatening complications involving the heart and blood vessels. Although the features are highly variable, most people with this disorder have a mutation in the same gene (FBN1).
FOR EXAMPLE:
Differentiation of Cells:
* Normally benign genes that, when mutated or expressed at high levels, play a key role in turning a normal cell into a cancerous cell.
* The normal silencing of such oncogenes is disturbed by faulty C-tagging of their DNA letters.
Oncogenes:
* Diana Bozza comforts her identical twin, Deborah Faraday, at an assisted living facility in Front Royal, Virginia. Diagnosed eight years ago with early onset Alzheimer's disease, Deborah is now completely disabled, while Diana shows no symptoms of the illness.
-National Geographic
Question #4: How can females express only one X chromosome per cell?
Calico Cats:
* Females have twice the number of X-linked genes as males.
*During embryonic development, one of the X chromosomes is inactivated into a structure known as a "barr body" in all female mammals.
*This leaves only one active X chromosome in each cell.
* X inactivation is completely random in each cell, therefore roughly half of all cells have one X chromosome inactivated while the other half have
the other chromosome inactivated.
* In female heterozygous cats, two different alleles for fur color are carried.
* Since each cell will inactivate a different X chromosome, a different allele will be expressed; the cat will be a patchwork of these two types of cells (colors).

Question #3: How can identical twin litter mates show different coat colors at birth?
Question #5: How do your actions as a ten-year-old not only affected your genes, but those of your future children and grandchildren?
* Epigenetic changes due to environment can occur even before birth.
* Scientists used to believe that epigenetic changes could not be inherited, as gametes are "reprogrammed" to have an epigenetically clean slate.
* Although most methyl tags are removed, studies have shown that some are still passed down from generation to generation.
Evidence for Inheritance:
* An isolated farming community, Overkalix, in north Sweden suffered from extreme fluctuations in food supply.
* Boys who had survived a year of famine while aged 9-12 went on to have sons and grandsons who lived on average 32 years longer than of those boys who had enjoyed a year of feasting.
* Girls who were born during a famine year went on to have daughters and granddaughters who had worse health outcomes.
WHY?
* Epigenetic changes of gametes are most prevalent during the development of gametes.
* Grandfathers who were over-nourished when their sperm were forming put their grandsons at risk of early death.
* Grandmothers who were undernourished in the womb—when their eggs were forming—put their granddaughters at risk.
Evidence in Fruit Flies:
Agouti Mice:
* Starting just before conception, mother mice were fed a diet rich in methyl donors, small chemical clusters that can attach to a gene and turn it off.
* These molecules are common in the environment and are found in many foods, including onions, garlic, beets, and in the food supplements often given to pregnant women.
* After being consumed by the mothers, the methyl donors worked their way into the developing embryos' chromosomes and onto the critical agouti gene.
* The mothers passed along the agouti gene to their children intact, but thanks to their methyl-rich pregnancy diet, they had added to the gene a chemical switch that dimmed the gene's deleterious effects.
THE END
Cites:
* Google Images
* National Geographic
* NCBI
* Mrs. Z :)
* Books: Epigenetics: How Environment Shapes Our Gene by Richard C. Francis, The Language of Life by Francis S. Collins, Genetic Twists of Fate by Stanley Fields and Mark Johnston, The Stem Cell Hope by Alice Park, The Mysterious Epigenome by Thomas E. Woodward and James P. Gills, The Agile Gene by Matt Ridley
Color-Blindness:
* Some female carriers of the red-green mutation are less sensitive to red-green differences while others can make finer red-green distinctions.
* Carriers end up with four types of cone cells: normal blue, green, red cone cells, and cone cells with the mutation-induced hybrid opsin.
hanks for watching homie
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