Fugu May Be Key To Human Genome

sulli writes ; "If it doesn't kill you first, it may get you a Nobel Prize. The fugu (puffer fish), best known for being a delicacy in Japan despite being poisonous if improperly prepared, has a very short genome (400M base pairs) compared to that of humans (3.5B base pairs). Says a sushi fan at DOE: "[W]henever researchers have gone into the fugu and looked for human genes, by and large they've found them." Info from a related project in the UK is here."

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The beginning

[H*rus]

Let me tell you how it all started:

In The Beginning
In the beginning there was the computer. And God said:
%Let there be light!
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%God
#Enter password.
%Omniscient
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%Omnipotent
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%Technocrat
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#Unrecognizable command. Try again.
%Create light
#Done
%Run heaven and earth
#And God created Day and Night. And God saw there were 0 errors.
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#Approx. funds remaining: $92.50.

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Open Source Genome

[sparcv9]

Of the 3.4 billion chemical building blocks that make up the human DNA strand, scientists believe only 3 to 5 percent represent actual instructions that make some people tall, some blue-eyed and some prone to heart disease.

/* ... the rest is comments and a copy of the GPL */

More about the puffer...

[Oscarfish]

...ripped from the link I posted just a couple of minutes ago.

It is fugu, a blow fish, that has the deadly nerve toxin in one of the internal organs (either the liver of gall bladder, I forget which). There are fugu restaurants in Japan, where the thrill of risking death by eating even a slightly tainted sliver of meat is the whole point of the experience.

You must be a licensed fugu chef to work at such a restaurant, but there are a number of "black market" fugu stands around, too.

However, fugu usually kills you within 15 minutes, not 24 hours. It starts with a tingling in the fingers, and works its way up your arms and legs, until you are completely paralyzed, and you die when it reaches your heart.

I'd guess that the fugu chef, and the doctor, were having a little fun at Homer's expense.

Spage Yee {sy}: This fish is poisonous because its innards contain tetratodoxin (TTX) which is a neurotoxin, which blocks either the sodium or potassium (one or the other it's been a while since I studied neurobiology) channels in your nervous system.

Michael T. Itamura refers the interested reader to the August 1984 issue of National Geographic. Stories and photographs of the leopard puffer. (Even a story about a famed Kabuki actor who ate the liver of the puffer and paid for it with his life). Quite interesting.

***

I'm actually watching tonight's episode (6:00p.m. where I live), 5F11, where the model UN gets stuck on the island - and Bart goes snorkeling to retrieve a cooler of food. There's a puffer fish waiting for him in the sunken school bus.

Homer eats the fugu...

[doorbot.com]

Dr. Hibbert: You have twenty-four hours to live.
Homer: Twenty-four hours!
Dr. Hibbert: Well, twenty-two. I'm sorry I kept you waiting so long.
Dr. Hibbert: Well, if there's one consolation, it's that you will feel no pain at all until some time tomorrow evening, when your heart suddenly explodes.
Dr. Hibbert: Now, a little death anxiety is normal. You can expect to go through five stages. The first is denial.
Homer: No way! Because I'm not dying!
Dr. Hibbert: The second is anger.
Homer: Why you little!
Dr. Hibbert: After that comes fear.
Homer: What's after fear? What's after fear?
Dr. Hibbert: Bargaining.
Homer: Doc, you gotta get me out of this! I'll make it worth your while!
Dr. Hibbert: Finally, acceptance.
Homer: Well, we all gotta go sometime.
Dr. Hibbert: Mr. Simpson, your progress astounds me.

no one single organism is the key

[myc]

Fugu is useful because of it's small genome size, but genomic information only tells you so much. Imagine not understanding computer code, and someone hands you the source code for the entire Red Hat distro; it's not very useful insofar as understanding how your computer works, unless you understand what the code means.

To truly understand biology you need a model organism that is accessible experimentally. A good model system should have the following traits:

(1) Genetically tractable: basically this means that you can reliably perform matings and score marker genes for mapping.
(2) Easy to culture: can grow large numbers of the organism in a relatively short time for relatively little money.
(3) Easy to manipulate: have the ability to generate both random and targeted mutations, have vectors by which to insert transgenes.
(4) Easy to observe: simple organisms that have transluscent body walls are the best.

Fugu doesn't have ANY of these advantages except the small genome, so probably the most use that will come out of it will be as a reference organism. Experimentally, the best model organisms biologists have are:

(1) mice: best characterized mammalian model. you can do targeted mutations and insert transgenes, but random mutagenisis is hard. Histology and embryology is pretty well established, but mice like most mammals are very complex and often studies raise more questions than answer them. Genome sequence note quite complete yet, but getting there.
(2) fruit flies: Drosophila melanogaster is a great model system. The genome is relatively small (about 10^8 base pairs of DNA, and estimated 15,000 genes), but it has all the relavent organs and systems as mammals, and many genes function in the same way. Genome sequence has been completed.
(3) nematodes: Caenorhabditis elegans is also a great model system. Genome size is approx. the same as flies. Has the added advantage of having its entire cell lineage mapped. It only has 1000 or so cells, so it makes a super model organism for studying differentiation. Genome sequence is also complete. Disadvantages is due to divergence from the mammalian branch, it does some things oddly, so not quite as similiar to humans as flies are.
(4) yeast: the bug you use to brew beer, Saccharomyces cerevisiae. Single cell eukaryote, in fact the first eukaryote to have its genome completely sequenced. Great organism to work on really basic things like DNA replication and repair, and basic cell biology, but obviously not great if you are interested in Alzheimer's disease or hypertension. OTOH good for studying some kinds of cancers. You can grow a TON of yeast in the lab easily
(5) bacteria: Escherichia coli is ever simpler that yeast because it is a prokaryote, it has no nucleus. But it is good for stufying really basic mechanisms such as protein folding, translation, etc etc. You can grow 10 TONS of E. coli in the lab easily :)

Also, some ppl study Xenopus lavis (African bullfrogs), Danio rio (zebrafish), chickens, rats, among others, but by and large the major model organisms that are studied in a way relavent to medicine are flies, worms, and mice, and yeast and bacteria to a lesser extent. Often different investigators will collaborate with each other in a cross-species manner, and compare results between organisms to look for common themes in common problems.


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