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10.6.10

Successful Day!

We passed inspection! All of our vehicles have all required signage
and lighting and all the bikes have all required reflective tape and
lighting. Everyone pulled together and ironed out all the details to
make it happen on time.

We finished up the day with a huge meal at Outback Steakhouse. On the
way back from the restaurant we discussed the difference between a
triplet repeat and a point mutation in FA. Mike Andresen gave us a
laymen lecture from the back of the rental car and brought us a little
closer to an understanding...now I realize many of you have no idea
what a triplet repeat or a point mutation is so here's my challenge:
For those that have a decent understanding of these concepts, please
post your explanation in a comment below. Perhaps we can all learn
something about FA and what causes it.

By the way I checked the analytics and we had 408 hits on this blog
yesterday! Biggest day ever! Thank you for spreading the word. Stay
tuned and tell a friend!

5 comments:

Spinner said...

A trpple Repeat - I have NO clue really, but can not wait to hear/see some others clear that up fort me;)

Donovan said...

Okay I’ll play,
The end game is to make a compound called Frataxin. (Simply put frataxin gets rid of used iron during energy production from the mitochondria)
So assume we are making a cake (the cake representing frataxin). Here is the recipe:
1) add the cake mix 2) add the milk 3) add the eggs 4) beat for 2minutes 5) place in oven at 350 degress 6)wait 30minutes and remove cake from over and cool.

With the triple repeats (meaning) GAAGAAGAAGAAGAA the recipe for the cake would be 1) add the cake mix 2) add the milk 3) add the eggs 4) beat for 2minutes 5) place in the oven. However note the last step is missing, so you never take the cake out of the oven and the burnt cake is not usable.

With the point mutation (made up example but you get the concept where the amino acids are out of sequence or missing) GGGAAGAGGAGAAAAGAA the recipe for the cake would be 1) add the cake mix 2) beat for 2 minutes 3) add the milk 5) add the eggs 5) place in the oven 6)wait 30minutes and remove cake from over and cool. Note that step 2 is now out of order and adding the milk and eggs without mixing will not produce a cake that is usable.

For those who need more information, the cake represents fraxatin, the recipe represents the DNA strand, the person doing the work represents the RNA.

Did I win???

Jen said...

OK - I can't resist a genetics question even when exhaused after a productive FA Cardiac Summit...

Warning - long post... (in fact after typing it all out I had to break it up into multiple posts so look for the sequels) anyone on the TEAM FARA with insomnia pre-race day should read this you will be out cold in no time!

Friedreich's ataxia (FA) is a genetic condition; meaning it results from a mutation in a gene. The gene linked to FA is called FRDA. We all have two copies of the FRDA gene - one from mom and one from dad. Genes code for proteins. The FRDA gene codes for a protein called frataxin.

I am going to use a letter and word analogy here; however I did like Donovan's recipe analogy.

You can think of a gene as a sentence.

"Tomorrow is the launch of RAAM."

Each letter of each word is an individual DNA molecule (If I were really creative I would have made a sentence only from the letters G, A, T, and C - the four deoxyribonucleic acids - DNAs)

Each word is a specific coding part of the gene called an exon. The spaces in between the words represent introns (non-coding parts of the gene).

So each letter in each word needs to be correct and all the words need to be present and in the proper order for the word to function properly and convene the necessary information. The FRDA gene needs the proper DNA sequence to make its associated protein, frataxin.

go to part 2

Jen said...

Part 2
FA is caused when there are mutations, or misspellings, in the DNA sequence of the gene.
The most prevalent mutation in FA is called a GAA repeat. In a non-coding region, intron 1, of the FRDA gene there is a repeating sequence of DNA, GAA.

"Tomorrow GAAGAAGAAGAAGAAGAA is the launch of RAAM."

We all have this GAA repeat in intron 1 of our FRDA gene however most people only have about 7-20 GAAs. These GAAs are in a non-coding sequence of the gene so they are normally cut out, ignored, when the gene is read (transcribed) to make frataxin.

95% of individuals with FA have an expansion of these GAA repeats - There can be 60-1500 of these GAA repeats.

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GAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAA
GAAGAAGAAGAAGAAGAAGAAGAAAGAAGAAGAAGAAGAAGAAGAA is the launch of RAAM."

So... even though these repeats are in an intron/non-coding sequence they still cause a problem because of their size and they basically cause the gene to not get transcribed or made to frataxin.

95% of individuals with FA have expanded GAA repeats in both FRDA genes so they can not make enough of the essential protein frataxin.

go to part 3

Jen said...

Part 3
When someone asks you "what are you repeats?" they are referring to the number of GAA repeats on each gene. (This is determined through genetic testing).

People sometimes ask about this because age of onset of FA and disease severity have been linked to the GAA repeats (disclaimer: this is not a perfect correlation... you have >30,000 other genes that are also important). That is because the length of GAA repeats also has been shown to correlate with amount of frataxin. So someone with 200 and 800 repeats might make 10% of the normal amount of frataxin and someone with 800 and 1200 repeats might make 2% of the normal amount of frataxin.

If you are still with me... what about the other 5% of individuals with FA? Those individuals have a GAA repeat on one gene and a different type of mutation called a point mutation on the other gene.

Keeping with the same analogy... a point mutation is a different type change in the DNA sequence; it could be changed DNA/letter (an A to a T), it could be a few DNAs/letters deleted, it could be a few DNAs/letters inserted.

"Tomorrow is the launch on RAAM." (here the f in of was changed to an n)

"Tomorrow is the lunch of RAAM." (here the a in launch is missing)

"Tomorrow is the laxunch of RAAM." (here an x was inserted in the middle of word)

If you are still with me then you might appreciate that different point mutations can have different levels of severity. Some only disrupt the gene sequence mildly and frataxin or something closely resembling frataxin can be produced. Other point mutations can completely alter the DNA sequence and result in no message or no frataxin.

So GAA repeats and point mutations are different types of mutations that can occur in the FRDA gene that lead to impaired transcription of the gene and decreased frataxin production.

I can't even remember at this point if I answered Kyle's question at this point so I am going to stop here and wish the entire TEAM FARA a good nights rest.

I am thinking of you all and wishing a successful, fun and safe adventure. I can't wait to see you in Annapolis.
Jen