h2g2 The Hitchhiker's Guide to the Galaxy: Earth Edition

I had a look at the "Human Prion Point Mutation" page George. Orcus was right. It's heavy going. I'll need a clear head and plenty of time to do it justice.

I read something interesting a little while ago that I bet you would find interesting. It was about Huntington's Chorea which is a prion-like disease (some suspect it actually is a prion disease). The proteins behave in a similar way to damage the brain. I haven't got time to tell you about it at the moment. It involved repetition of the codon cag cag cag cag - sometimes more than 100 repetitions. Anyway, if I forget, remind me ... unless you already know about it.

Speak to you later.

Sal

Remember that Prion report I was due? Whell, now it's due tommorrow, so i have to bog down. Talk to ya later.

Hey Sal, I went on a conference once that went on about that. You are correct, Parkinson's is also like this, a lot of neurogenerative diseases are quite closely connected to prion disorders in fact.

Programmed cell death (called apoptosis - our cells die after approximately 50 divisions) is controlled to some extent by repeated DNA strand endings like this called telomers. There's an enzyme called telomerase that chops a bit off every time a cell divides. When the telomer gets to a certain curtailed length the cell dies and stops dividing. This is one thing that is being looked at to extend our lives - inhibit telomerase somehow.
I personally think this would be a terribly bad move. We have a name for cells that don't ever stop dividing, they're called malignant! Stop programmed cell death and you may have cancer .

Good luck with that George! Let us know how you get on.

I've heard of telomers Orcus and, funnily enough, that's exactly what I thought when they were talking about finding ways to stop them shortening. You'd think that the danger of cancer would be obvious to them, wouldn't you?

Now you come to mention it, Parkinsons does look like one of the diseases. Sufferers certainly lose co-ordination. Does it also affect their reasoning ability, memory - that sort of thing?

That thing about Huntington's Chorea was really interesting. Apparently, if the gene responsible for Huntington's is missing altogether, the person has a different disease: Wolf-Hirschhorn syndrome. The gene has this one word, "cag", repeated over and over again in the middle of it. There can be anywhere between 6 and over 100 repetitions - 10 to 15 being the normal range. If you have fewer than 35 repetitions, you should be ok. More than 38 and you'll get the disease when you're middle aged or younger (depending on the number of repetitions). The more repetitions the younger you'll get it. The symptoms sound very similar to CJD and sufferers can have it for 15 to 25 years before it finally kills them. It's particularly nasty for the families of sufferers because, not only do they have to watch the slow, horrible deterioration of their relative, but they have to worry about whether they or their children have the disease. Because it usually strikes when the person's older, they've had time to have children before they know they have the disease. Possibly by coincidence, studies have indicated that in families that carry the disease, the members who actually have the mutated gene have more children than those who don't. It's a dominant gene, so you don't need to have more than one copy to suffer from the disease. The disease is worse if the gene is inherited from the father and the older the father the worse the disease in the off-spring. Apparently, as men get older, more copying errors are made in the DNA in their sperm and the number of "cag" repeats increases. ALSO there are several other similar diseases caused by "cag" repeats in other genes. AND there are several yet other diseases caused by other codon repeats that start with a 'c' and end with a 'g'. All the diseases were of a neurodegenerative nature and there's speculation that a codon "c?g" repeated in the same way in just about any gene might cause similar diseases.

Anyway, I thought it was jolly interesting and I thought you all would too.

Sal

That *was* jolly interesting, Sal! I see the beginnings of an article on neurodegenerative diseases in general there...

My, Sal, you are well read! Yeah I'd heard all that, but its kind of moy job and not yours, I'm impressed .

BTW, I'm glad I'm not the only one who has thought this might be a probelm with the cancer thing. Nice to meet a fellow sceptic/believer.
We die at the time we do for a reason. Nature!

Here I am, procrastinating as usual. I'm only on page eight, and I've got exactly eight hours before I have to turn the report over. Iritatingly enough, I also have two tests and a fourty-minute oral presentation tommorrow as well. To quote the misery chick, "Life sucks, don't be fooled by location changes."

Who's the misery chick?

Sounds like "Daria" to me...

Thought you might think it was interesting

Guessed you'd know all about it Orcus. Honestly, all the little treasures you must be keeping to yourself!

On the subject of putting off the inevitable, did you see that they've managed to extend the lives of mice to (I think) more than double their natural span by delaying breeding over several generations? They reckon if humans go on the way we are in the west, with people delaying having families until they're older, in time, that in itself will extend life expectation. I'm not going to have any children at all, so I should live for ever, don't you think?

Oh, that's a shame Sal

That is the sort of thing that would put an evolutionary pressure on to live longer but there are other factors (coronary problem for example). How does this get around menopause? That's not an easy thing to get around - evolutionary speaking. Humans have a pretty unusual sexual cycle in the animal world, not sure its all that comparable to mice. (not sure I could cope with a once a year rutting season like deer have )
Who would want to look after a tennager at 70? . I know I wouldn't want to have looked after me when I was 15!

I'm just getting my own back on my genes for trying to control me just showing them who's boss.

You're probably right. If it worked at all, it would probably take quite a few generations of people waiting till just before the menopause to start their family. One of the unusual things about human females is that they live so long after losing the capacity to reproduce. I wonder how long that peculiar but useful quirk took to evolve.

My next door neighbours (over 60 years old) have about 5 or 6 grandchildren deposited with them every weekday while the parents go to work. Then, at the weekends, they get all their adult kids as well as the school aged kids, babies and toddlers. What a nightmare. There's no escape. I wonder if they'll last till they're 70 - poor devils.

Orcus - once a year? That often?

Well, I live in hope

George, have you mentioned Chronic Wasting Disease (very like BSE in cattle) in your report? I heard an item on last night's news about a problem they're having in Colorado and some other areas with the disease in elk. They were saying that there had been some (about 3 I think) mysterious cases CJD and the thing all the sufferers had in common was that they had eaten these elk. They thought that something like 30% of one herd had CWD and they wondered how it was being passed from one animal to another. They also said the authorities were making all sorts of comforting noises about how humans couldn't get it - exactly as the British government did when BSE first came to light here. Anyway, if you haven't included anything about it, I guess it's a bit late now. Hope you got it in on time.

Sal

Hi! Yes, I did mention CWD and a few other diseases and theories. I opened with a page-long quote from Chritons "The Lost World" where it mentioned prions. And I stayed up way too late typing the final draft. The worst part is, I don't think my prof. will even read the whole thing. Thanks for all your help!

~George~

Sorry, no response to my report yet. Prof Connoly takes forever to grade papers.

You describe two mechanisms by which abnormal prions may arise - infection with already abnormal prions and a genetic route. Does that mean that no abnormal prions can occur other than by infection or inheritance.

The evidence of prion invulnerability raise an eyebrow or two (I only have two). A prion is a protein. Are there any other proteins which cannot be broken down by digestion, extreme heat, rotting, etc?

Hiya Mund. Nice to see you over here. Sorry to have neglected your message for so long. I haven't been able to do this for a few days. Anyway, to answer your questions ...

No, it doesn't mean that no abnormal prions can occur other than by infection or inheritance. Actually, I think I mentioned that somewhere in the region of 90% of CJD cases arise sporadically. The prion research is real cutting edge stuff and there's a lot to learn. Orcus was saying on one of the threads on the unedited version of this article that current research results suggest that ALL proteins can potentially behave like prions. There's some interesting speculation on the old threads. We talked about various possible modes of transmission and there's some chat about the possibility of organophosphates playing a role in triggering the outbreak of BSE. If you want to have a look at the threads on the unedited version, it's here http://www.bbc.co.uk/h2g2/guide/A480638

I've never heard of a normal protein being so tough to break down.

Any news on the report front yet George?