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Old 09-01-2002, 02:30 PM   #141
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Quote:
Originally posted by scigirl:
<strong>I think you are still hung up on that one telomere breaking study. In this particular case, no telomeres were broken off. They are still there.</strong>
One obvious thing we may be overlooking is to explain what a telomere is. It's not a discrete, unitary structure -- it's a long stretch of DNA, on the order of 10,000 bases, which contains nothing but a short sequence (TTAGGG and its complement in humans) repeated over and over, thousands of times. You can have a break in a telomere and still have a telomere present.
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Old 09-01-2002, 02:31 PM   #142
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Vanderzyden seems to be especially interested in the "hows" of the fusion event (are you an engineer perhaps! )

Here's that article again - I just might have to get this from the library on tuesday and read it in its entirety.

Quote:
Possible mechanisms underlying the formation of various types of Rb fusion are discussed here. For example, Rb fusion in wild mice involves complete loss of p-arm telomeres by chromosome breakage within minor satellite sequences. By contrast, interstitial telomeric sites are found in the pericentromeric regions of chromosomes originating from a number of vertebrate species, suggesting the occurrence of Rb-like fusion without loss of telomeres, a possibility consistent with some form of telomere inactivation. Finally, a recent study suggests that telomere shortening induced by the deletion of the telomerase RNA gene in the mouse germ-line leads to telomere loss and high frequencies of Rb fusion in mouse somatic cells. Thus, at least three mechanisms in mammalian cells lead to the formation of Rb fusions.
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Old 09-01-2002, 02:38 PM   #143
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pz,

Thanks for your telomere clarification!

That makes a little more sense now, why Williams would say "Well there's a telomere in the middle of chromosome 2."

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Old 09-01-2002, 02:45 PM   #144
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Browsing around trying to answer my own question from a while back, I found this...

Molteni L, De Giovanni-Macchi A, Succi G, Cremonesi F, Stacchezzini S, Di Meo GP, Iannuzzi L

Institute of Animal Husbandry, Faculty of Agricultural Science, Milan, Italy.

A new Robertsonian translocation has been found in cattle. A bull from Marchigiana breed (central Italy) was found to be a heterozygous carrier of a centric fusion translocation involving cattle chromosomes 13 and 19 according to RBA-banding and cattle standard nomenclatures. CBC-banding revealed the dicentric nature of this new translocation, underlining the recent origin of this fusion. In fact, both the bull's parents and relatives had normal karyotypes. In vitro fertilization tests were also performed in the bull carrying the new translocation, in two bulls with normal karyotypes (control) and in four other bulls carrying four different translocations.

from

<a href="http://www.gate.net/~rwms/hum_ape_chrom.html" target="_blank">http://www.gate.net/~rwms/hum_ape_chrom.html</a>

fusions in sheep, mice also found.

Summarising what I understand of that page, not only is chromosome fusion observed going on right now (independent of the mechanism), it doesn't seem to have a necessary impact on fertility (which is what I wondered about).

In essence, arguing that chromosome fusion can't happen seems futile - it does happen. Maybe you (VdZ) need to take another tack?
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Old 09-02-2002, 12:58 AM   #145
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Slightly OT, but does anyone know what kind of even is thought to have happened with the divergence of the horse and donkey species? The donkey has 62 (31 pairs) of chromosomes while the horse has 64 (32 pairs) of chromosomes. Does anyone know if the difference is thought to have been a breakage or a fusion event? It's kind of hard to deny that these are closely related species-- production of sterile hybrids w/ occasional fertile hybrids (1 in 10000). If there is evidence of a fusion event (like in humans), it seems there would further support here for the contention that chimps and humans had a common ancestor. If not here, perhaps someone else is aware of closely related species with indications of a fusion event similar to that which happened in hominid ancestors.

[ September 02, 2002: Message edited by: Dan828 ]</p>
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Old 09-02-2002, 12:24 PM   #146
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Quote:
Originally posted by scigirl:
<strong>

T--&lt;--p---c---p--&gt;--TT--&lt;--p------c------p--&gt;--T

If indeed 2q and 2p fused like this, you would have the following features in the new chromosome:

1) Two centromeres (if the chromosome were to become functional, then only one of the centromeres would be used in meiosis and mitosis).

2) Two "real" telomeres - one at each end - together with their pre-telomeric sequences pointing in the correct orientation (in this case, towards the telomere).

3) Two extra telomeres at the fusion point (i.e. in the middle of the new chromosome). Also, you would find two extra pre-telomeric sequences but in this case, they would point away from the "real" telomeres or ends.

4) Oh and of course, the new chromosome length would equal the length of 2p + 2q.

Ok that's the fusion prediction.

</strong>
Wait, wait...not so fast!

Looking a bit further, I found the (Adobe PDF)article at the PNAS website:

<a href="http://www.pnas.org/cgi/reprint/88/20/9051.pdf" target="_blank">http://www.pnas.org/cgi/reprint/88/20/9051.pdf</a>

Let us consider some of the misleading and oversimplified details. This very short paper reads more like propaganda than the findings of objective scientific research.

Quote:

page1, pp 1: Molecular data show evidence that this event must have occured only a few million years ago (refs 4 and 5 and the references therein).
As I have indicated elsewhere at length, there are tremendous difficulties in the construction and comparison of phylogentic trees and so-called "molecular clocks."

Quote:

page1, pp1: Although the precise nature of this putative fusion is unknown, cytogenetic data point to either a centromeric or telomeric fusion in the vicinity of region 2q1 (1,2, and 6).
Notice here that they are unsure if a centromeric or telomeric fusion occured. However, no where in the paper do we find exclusion of centromeric fusion. Furthermore, it would seem that additional complications arise if we consider fusion of the centromeres.

Here we also have the first indication that far too much hand waving going on. Putative means commonly accepted or supposed. It is as though the fusion has already been conclusively demonstrated elsewhere. This is the equivalent of the schoolyard rant, "Everybody knows that simple fact". But of course, rumors are often found to be false. I imagine that the references cited here are merely more hypothesis of a supposed fusion. Furthermore, the attempt to demonstrate the existence of physical vestigal evidence is the precise focus of this article. And yet, the authors go on to an immediate conclusion that the "fusion point" itself is commonly accepted:

Quote:

page 2, pp1: To investigate the architecture of this putative fusion point, we isolated genomic cosmids containing the telomere-like repeats from band 2q13.
But, how can it be a widely accepted fusion point? Surely this is an exaggeration if (1) this is the first (and only?) study and (2) the findings indicate that the sequences in question are only "telomere-like".

There are more problems. Moving to page 4:

Quote:

Flanking sequences are characteristic for the preterminal regions of human chromsomes.
Just what does this mean, anyway? Characteristic of what? Well, we are not told. The very next two sentences, however, are even more confusing:

Quote:

The data we present here demonstrate that a telomere-to-telomere fusion of ancestral chromosomes occured, leaving a pathognomonic relic at band 2q13. This fusion accounts for the reduction of 24 pairs of chromosomes in the great apes (chimpanzee, orangutan, and gorilla) to 23 in modern human and must, therefore, have been a relatively recent event.
The data doesn't mirror telomere sequencing. It is only "telomere-like". In fact, the amount of data seems obscure. Incidentally, can someone tell me from the Methods section on page 3: What is the length of the "telomeric" arrays that were observed? How many sequences?

How amazing, then, that such conclusions are drawn from the foregoing!!! This is a single study, which itself would seem capable of several interpretations. And yet we are told that this is proof of a reduction from 24 to 23 chromsomes! Also, we must be suspect since we do not see any other possibilities considered.


Scigirl, you wrote:

Quote:
Originally posted by scigirl:
<strong>

However, you are correct in stating that chromosome fusions can be a problem in some cases.

</strong>
Well, if you input "fusion telomeres tumor" into the Google machino you will find plenty of things like this:

Quote:

Chromosome fusion due to the loss of telomeres was proposed to lead to chromosome instability in plants more than 50 years ago by Barbara McClintock.

<a href="http://www.ucsf.edu/pibs/faculty/murnane.html" target="_blank">http://www.ucsf.edu/pibs/faculty/murnane.html</a>


Telomeres protect chromosomes from degradation and fusion.

<a href="http://www.geron.com/02.01_telomerase.html" target="_blank">http://www.geron.com/02.01_telomerase.html</a>


Telomeres protect chromosome termini and prevent chromosome rearrangements such as end-to-end fusion and illegitimate recombination.

<a href="http://www.uthscsa.edu/csb/faculty/sakaguchi.html" target="_blank">http://www.uthscsa.edu/csb/faculty/sakaguchi.html</a>


Without telomeres, the ends of the chromosomes would be "repaired", leading to chromosome fusion and massive genomic instability.

...cells can continue to divide and telomeres continue to shorten until the M2 (Mortality stage 2) mechanism is induced. M2 represents the physiological result of critically short telomeres when cells are no longer able to protect the ends of the chromosomes, so that end-degradation and end-to-end fusion occurs and causes genomic instability and cell death. In cultured cells, a focus of immortal cells occasionally arises. In most cases, these cells have reactivated the expression of telomerase, which is able to repair and maintain the telomeres.

<a href="http://claim.springer.de/EncRef/CancerResearch/samples/0001.htm" target="_blank">http://claim.springer.de/EncRef/CancerResearch/samples/0001.htm</a>

Let me be clear: I am insisting that chromosome fusions are always problematic.

Even the authors' example of supposedly similar fusion is one of abnormality (cancer):

Quote:

page 4, pp2: Fusion of telomeres is a rare occurence in normal lympoblasts and fibroblasts, although it has been observed in 20-30% of the cells of certain tumors, where it appears to be nonclonal (25-29).
And yet somehow, the authors don't realize the implications. All supposed "fusions" (whether telomeric, Robertsonian, etc.) produce genetic abnormality. So, if a end-to-end telomeric fusion occured in the supposed common ancestor, the progeny would not become the root for a new species, but rather ill-suited life at all.

Permit me to make one additional observation. We can see why Williams was lacking confidence regarding the supposed vestigal centromeres, since there is apparently no published data to support it:

Quote:

page 4, pp2: The telomere-telomere fusion at region 2q13 must have been accompanied or followed by inactivation or elimination of one of the ancestral centromeres, as well as by events that stabilize the fusion point. Hybridization studies suggest that there is a remnant of an ancestral centromere at band 2q21, which is consistent with the telomeric fusion proposed here (A.B, unpublished data).
There are additional problems with the remainder of this paper, but I will stop here.

This "demonstration" of chromosome fustion is hardly convincing. Unless there are any others that supersede this presentation, then I think it is safe to set the "fusion" issue aside.

Vanderzyden

[ September 02, 2002: Message edited by: Vanderzyden ]</p>
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Old 09-02-2002, 12:37 PM   #147
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Quote:
Originally posted by Vanderzyden:
<strong>Let me be clear: I am insisting that chromosome fusions are always problematic.</strong>
And you would be wrong. You are misreading your sources.
Quote:
<strong>
Even the authors' example of supposedly similar fusion is one of abnormality (cancer):

quote:

page 4, pp2: Fusion of telomeres is a rare occurence in normal lympoblasts and fibroblasts, although it has been observed in 20-30% of the cells of certain tumors, where it appears to be nonclonal (25-29).

And yet somehow, the authors don't realize the implications. </strong>
Rather, you are unaware of the meaning.

Cancer cells have a very high incidence of chromosomal abnormalities as a consequence of poorly regulated replication. You are confusing cause and effect.

Notice also what it says about normal lympho- and fibroblasts: you can sometimes find them with these kinds of fusions. The implications of that are that abnormality is not a necessary result of fusion.
Quote:
<strong>
All supposed "fusions" (whether telomeric, Robertsonian, etc.) produce genetic abnormality.</strong>
This is plainly and simply false. As I've already pointed out to you, Robertsonian fusions, though rare, happen all the time. Often, the individuals who have these things aren't even aware of it unless they are karyotyped.
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Old 09-02-2002, 02:28 PM   #148
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Vander,

I am having trouble downloading stuff at the moment, but I will read that article when I get a chance.

In the meantime, allow me to clarify a few things. You read up more on this chimp-chromosome fusion, and lo and behold you find out that it's complicated! Then you read words like "maybe" or "putative."

You find out that scientists aren't absolutely sure of a lot of things and use terms to reflect that uncertainty (heh and you had informed us earlier that we were all dogmatic!).

So your reaction to this newfound discovery about how scinece works. .. is to reject outright the scientific theories themselves? In favor of. . . well in favor of what, Vanderzyden? Your infallible Bible? That doesn't contain words like "putative?"

Vander, I want to ask you how you found out that the details behind this chromosome fusion is complicated? Was it in your Bible? It wasn't? Did your pastor tell you it was complicated? He (she?) didn't?

Oh, you found out it was complicated from those dogmatic evil scientists? Those scientists that spend their careers studying an aspect of biology in order to understand it better? Ok, so you accept some of their data, but you don't accept any of the conclusions that these same scientists made from this data?

Vanderzyden - I encourage you to read any genetics paper that does not directly pertain to evolution. A paper on cancer, or on an autoimmune disease. You will find the exact same types of terms - maybe, putative - and the exact same types of complexities!

Please please please answer me - why are you only criticizing the papers with evolutionary implications, but not the cancer papers which use the exact same methods, inferences, and terminologies?????

I don't understand you.

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Old 09-02-2002, 02:31 PM   #149
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VZ, you must not read a great deal of scientific literature: That's the way it's normally written!! They teach us to use the passive voice, and to use "weasel words" to indicate that our hypotheses are tentative!" They are tentative because all scientific knowledge, unlike religious knowledge, is, by definition, tentative.
Also:
"putative (adj) Commonly thought or deemed; supposed; reputed." Webster's New International Dictionary, 2nd Edition. The word is typically used in the second shading in science: "Some folks say it's that way, but we're gonna test to see if it meets this new criterion."
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Old 09-02-2002, 04:12 PM   #150
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RED HERRING ALERT!! RED HERRING ALERT!!

Notice that Van has done a nice job of attempting to derail the discussion -- if you don't like the content of a paper, attack its wording... I have lurked on these boards long enough to recognize this approach -- highlight all of the "weasel words" in a scientific paper to somehow indicate that it is mere speculation. Would he have believed the paper's conclusions any more strongly if the scientist had used words like "shows", "proves", and "without a doubt?"

So, where have we really gotten? I think that Van. is accepting that fusions occur now. Fair enough? That is progress.

Now he has to argue that they are always fatal or at least always have crippling effects that would prevent reproduction. Note that he is stuck -- he can't argue merely that they usually have deleterious effects, since nothing would have prevented one of our ancestors being the lucky surviver of a fusion event.

Should be fun. I'm learning a lot. Perhaps the next argument will be "fusions can occur, but this doesn't happen to be one." I look forward to learning a lot more about the details of gene sequencing in that case...

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