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Genetics and Myeloproliferative Neoplasms (MPNs)

Coming to understand modern genetics is a bit like learning a language.  It’s foreign and impenetrable at first. Over time, with study and exposure it becomes more familiar. The first steps are the most difficult, but if we persevere we can end up enriched by the wonders of molecular biology and the miraculous flow of cellular interchanges that make up life itself.

The course title for our colloquium defines the material we’ll be exploring together:  the life cycle and function of our genes and the nature of our myeloproliferative neoplasms.

Genetics is about DNA (deoxyribonucleic acid) and genes, about the transmission of traits and the functioning of each cell in our body. .Since we are concerned with the form and function of biological molecules, the focus of this seminar is on molecular biology.

A gene is a stretch of DNA that encodes data to produce a protein to perform an action.  DNA, in the nucleus of every cell in our body, contains the instructions necessary for the cell to perform its functions.  These instructions are encoded in the form of four nucleotides made up of base pairs G and C, A and T.(Guanine and Cytosine,  Adenine and Thymine) plus sugar and phosphate.  On average genes are about 1000 to 10,000 base pairs in size, but some genes are much larger.

Myeloproliferative neoplasms are genetic disorders affecting hematopoeisis, blood production. The genetic instruction set within the hematopoeic system has mutated to produce an excess of one or another blood cell lines or otherwise impair the proper functionality of blood cells.  Our practical object in learning how biology at the molecular level works is to help us understand and sort through the genetic discoveries designed to slow or reverse the progress of our MPNs.

There are seven elements to this first seminar module: 1. A graphic tour of concepts; 2. a DNA cartoon; 3. vocabulary building; 4. a summary printout of genetic terms; 5. an MPN application;  6. an exercise in building a DNA molecule; and 7.  concluding visual aids.

Suggestion:   Much material in this seminar will be opaque in the beginning and become clearer only as we move along. Best bet is to get a notebook to hold your notes on each module and write down the vocabulary. Repetition of these terms and seeing their interaction in future modules will eventually make them familiar.   In beginning this work, there are several aids available to us. :

(1) Start with the Genetic Science Learning Center site of the University of Utah. At http://learn.genetics.utah.edu/  When you arrive at this site:

Tour the BASICS (Click Upper Left)

Then choose each of these topics in turn.

What is DNA

What is A Gene

What is a Chromosome

What is a Protein

Note: You might have to click on NEXT in some cases to advance the narrative

===============================================================

(2) Look at DNA structure on DNA Tube, a short, technical cartoon.

http://www.dnatube.com/gvideos.php?viewkey=a1a4f25f62e0eb5261ca&urlkey=dna_structure&gid=26

===============================================================

(3) Vocabulary

Learning the vocabulary is made much easier by the talking glossary put together by the National Human Genome Research Institute. Here, you can hear  and see leading scientists present these words.. It’s important to learn the pronunciation of these unfamiliar terms so we can use them in talking with our hematologists…. and, of course, impress our friends.,

http://www.genome.gov/glossary/index.cfm?id=145   Learn and Review these 12 terms

Allele

Amino Acid

Base Pair

Cytosine

DNA

Gene Expression

Histone

Nucleotide

Ribosome

RNA

Telomere

Transcription

=================================================================

(4)  (Handout )

http://www.genome.gov/18016863

A brief guide to genomics fro NHGRI, downloadable.   Print this short guide and tuck it in your notebook as it will give us a common frame of reference.

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(5)  MPN and genetics:  The HDAC Affair.

The current  MPD Foundation Newsletter as well as several postings to MPD-Net reported promising results on HDAC inhibitors. Instead of just sliding by that news, let’s try to figure out what it means.  HDAC is an abbreviation for  “histone deacetylase.”  Histones ,which act as a spool around which DNA is wound within the cell nucleus,  are small proteins electrically attached to DNA. Histones play a role in gene regulation. “De-acetylase” is to effect gene expression by reducing the acetylation of the histone thus “inhibiting” the expression of a target gene.  HDAC inhibitors also act on nonhistone proteins like gene transcription and growth factors.

Why this works:  Acetylation of the lysine residues at one end of the histone protein removes its positive charge reducing the affinity between histones and DNA.  In most cases histone acetylation enhances the ability for a gene to reproduce itself while histone deactylation represses transcription.

For a graphic look at the process go to http://www.youtube.com/watch?v=4b-NSWm24BA&feature=related

Vocabulary:  acetylation, inhibiting, gene transcription,

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(6) Exercise:  Build a DNA Molecule.  Review material by playing this video game. http://learn.genetics.utah.edu/content/begin/dna/builddna/

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(7)  Videos

(Very brief and dramatic microscopic film, a must-see if you have ET)

http://www.youtube.com/watch?v=6R-ESPFiKbo

Megakaryoctyes breeding platelets

Dr, Stephen Sullivan, Bucks County Community College,

http://www.dnatube.com/gvideos.php?viewkey=deb67d7ce42d58fe5157&urlkey=dna_structure&gid=26

Very clear slide presentation, about 10 minutes, on DNA, proteins, cell division. Definitely do your vocabulary work before viewing this presentation.

Barry Schuler Introduction to Genomics http://www.youtube.com/watch?v=_xJXZBCOWMY&feature=related

A  21 minute visionary overview and projection of future genetic applications

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Feedback, questions to incorporate in next week’s discussion, send to: zhenyasenyak@gmail.com.

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