Why, on a molecular level, does non-disjunction of the 21 chromosome cause Down syndrome? Why is it so bad to have an extra chromosome.
Or have we not figured this one out yet?
It has been known for some time what part of Chromosome 21 is reponsible for most of the symptoms, but as far as I know, it is not yet clear exactly which gene or genes are responsible, and what exactly they do. See http://www.lifesciences.napier.ac.uk/courses/projects/downsynd/genes.htm But I don’t know how recent that page is, so more may be known now.
Like bibliophage said, I don’t think it’s yet been worked out to a molecular level for Down syndrome specifically. But as to your second question - Why is it so bad to have an extra chromosome? - THAT I can answer. Somewhat.
Trisomy-21 is unusual in that the person actually survives. There’s only one other somatic trisomy (ie, not XY) that doesn’t kill the zygote very early. I forget which one. 21 is one of the smaller chromosomes, so there’s not all that much extra genetic material lying around, so the effects are surviveable.
In general, it’s bad to have extra DNA because all of the genes in the body are very precisely regulated, and the regulation is based on the case of two copies of every chromosome. When an extra copy is thrown in, you’ll start getting genes over- and underexpressed, and since signal transduction pathways tend to form tangled messes, any problm quickly gets amplified and leads to Bad Things.
What if you had three copies of every chromosome (let’s say XXY for the sex chromosomes)? Would balance be restored? Or say four copies, if you need to have an even number?
tiploids, quadroploids, and other n-ploids are common in plants. however, usually only organisms with even numbers of chromosome sets reproduce properly, as it takes an even number of sets for meiosis to occur properly. n-ploidy is much less common in the animal kingdom, but not, i believe, unheard of. the basic rule in evolutionary biology seems to be (as it is with quantum physics): if it is not expressly forbidden, then it probably occurs somewhere.
-b
The Merck Manual lists trisomy of the following chromosomes: 18, 13, 8, 9 and partial trisomy of 22, in addition to 21. Trisomies of 8 and 9 do not result in a very early death. Full trisomy of 22 has occured in viable individuals. So, trisomies of 8, 9, 21 and 22 do not result in death within, at the most, one year of birth. There are also other chromosomal defects that are viable: deletion of the short arm of 4,5, and 13. There are also translocation defects that do not cause death at a very early age.
Thanks for the research, barbitu8.
Zen - at least in humans, extra sets of chromosomes are lethal. If you want a mechanism for why it’s lethal, I could probably make one up. I know, for instance, that in some organsims there are pathways that sense the ratio of the amount of DNA to the total volume of the cell. Something like that would be messed up with extra sets.
Plants and lower animals seem to be able to tolerate extra DNA pretty well, as bryan said, (watermelons are octaploid, for instance, IIRC), but we can’t.
Really? All of them? That’s bizarre.
Zen asks about an extra set of chromosomes. That condition is called triploidy, and is sometimes, but not always lethal, but is associated with severe birth defects and mental retardation.
Triploidy almost always occurs from simultaneous fertilization by 2 sperm. Using a nomenclature system where 46XX is a normal female and 46XY a normal male, triplod individuals can be 69XXX, 69XXY, or 69XYY. The 69XYY seems to have the lowest rate of livebirth.
Here is a link:
http://www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=214
Actually, I think I was wrong. Seedless watermelons, in particular are either 3N or 5N. Something common is octaploid, though. Strawberries, maybe? I forget. See, there’s a trend in plants that the more copies of the genome there are, the larger the plant is. So lots of food plants are polyploid.
But the fact that odd numbered ploidy plants have trouble reproducing is also exploited. That’s why I say watermelons are either 3N or 5N. They’re seedless because the seeds get screwed up during meiosis and die. Bananas are triploid, too. The part of the banana plant we eat is actually the seed pod. Diploid banana pods are filled with several large black seeds with a little pulp around them. But when they’re triploid, the seeds can’t form and it all fills up with pulp, which we eat. Ahh, the wonders of plant genetics.
Whats the point of plants having so many copies of the same gene? Also whats the point of plants that are diploid for a life stage (sporophytes), and then turned gave rise to haploid organisms (gametophytes), and then gave rise to another diploid stage again. I never got why it was good for the plant to keep switching between haploid, and diploid states.
Okay I should have previewed that one.
That’s something I hadn’t heard of! Do you have a reference so I could read up on it? (Something not too technical, please! IANABiochemist!)
Goat - I’m not aware of any good, definitive answers to those questions. It does seem to be common to find polyploids more in extreme environments. When you have extra chromosomes, you can mutate some of them faster than usual, because you still have good backup copies, thus increasing the speed of evolution. That’s one possible use for it. And a lot of the fruits I mentioned have been made polyploid artificially specifically to get more food.
I don’t know enough about plant life cycles to be able to comment intelligently on your question about 1N/2N life cycles. Sorry.
rjk - Sorry, I don’t. The best I can do is tell you that I heard about it in reference to sporulation in bacteria in a class a year or two ago. IIRC, the idea was that you had two interacting proteins. One was bound to sites on the DNA and the other was freely diffusing. The amount of free protein in the cell was therefore linked to the amount of DNA in the cell. The free protein acted as an inhibitor of some sort, so when the DNA was replicated, there was less free protein inhibiting whatever it was inhibiting, and the signal was passed on.