MedGen

Thankfully the situation is not as bad as in the states, but there is a little bit of good 'ol American evangelism being slipped in under the radar, via Ken Ham and AiG mostly.

Anyone else catch this last night? For UK members its available from 4OD, for our overseas members then it may be available through Youtube pretty soon. I was a little disappointed to see that creationism is still so rife in our country, but overall it was nice to see that it might get a few people to really re-consider what they know about evolution. Parts 2 and 3 are shown over the next two weeks on channel 4.

Isn't Sephadex just the type of cationic bead used in the column for size exclusion chromatography though. Gel electrophoresis technically has an aqueous nature, the running buffer, the solution of DNA and the running dye. So it is just a form of chromatography as well in a way. The gel is the stationary phase and the buffer/DNA solution is the mobile phase, and its aqueous. I need some clarification as to whether this is meant to be isolation or separation, hello OP? Hello?

I think its more the stop-start nature of lagging strand replication that made me nit pick. I'm a bit of a stickler for using correct terminology and descriptives for that sort of thing, even where it blatantly doesn't make a difference. An odd foible of mine perhaps.

It makes sense that the snoRNA's are derived from rRNA genes as these are the targets of snoRNA, and they also all appear in the nucleolus. The rRNA is transcribed and the small and large units "put together" here, but obviously only in eukaryotes.

Books are not infallible you know. As a basic representation of an E.coli replication fork, the above diagram from e.coli is correct. It is for all intents and purpose "Y" shaped. There happens to be a "V" in there as well otherwise it couldn't be "Y" shaped could it? [nitpick]The correct answer from the options is a little misleading, either that or I'm reading it wrong. It doesn't seem to account for the nature of the lagging strand. Am I just seeing a complication where there isn't one?[/nitpick]

Very confusing, the thread title says separation, but in the OP it says isolate. Gel electrophoresis isn't really used for isolation from other cellular fractions, which is what I thought the OP was asking about.

Well there's a reason agarose and polyacrylamide are used for separating DNA. The molecules form cross links when setting that form an intricate lattice work throughout the gel. Depending on the concentration of gel solute used (agarose normally for DNA) defines the size of the lattice and how big the gaps are. The higher the concentration the more crosslinks form, the tighter the lattice, the better the separation between similarly sized bands. Separating in water would just make them all migrate to the cathode at the same time, no separation. You need a medium that will retard the migration of different sized molecules, hence the whole point of using gel for electrophoresis.

I'd go for biochemistry, that way you'll have an advantage, either that or molecular biology and genetics...not that I'm biased about them of course. No sir.

Possibly by TF or RNA localisation during differentiation and in progenitor cell types. Histone methylation is more associated with an epigenetic "memory" than with differentiation, perhaps you meant Histone K acetylation? I had a quick gander of at PubMed and couldn't find anything to suggest an enhancer or epigenetic regulation. Anyone's guess.

No idea, this is just some preliminary info I got from a cattle breeder, I don't even know what breed they are. I'm still waiting on numbers and other info. They sire and the dams may have only been genotyped for the mutant and wildtype allele though, which of course would not give any new information. I'll try chasing up the breeder and see what he says about it.

Well some of them also code for siRNA's and miRNA's so they are transcribed/spliced, but I'm not sure of the mechanisms for that. Otherwise, IIRC, they are earmarked for degradation.

This is not an experiment, it is an observation that I was told about. I did a little literature researching and turned up the LaPointe et al, 2000 paper as well as some press releases from the ASA. That is all background information. Essentially I was asking if anyone had encountered and inheritance pattern like this before? As I have said already, I previously suspected the mutant allele is epistatic to another unknown loci. Is there anyway of determining whether or not an allele is hypostatic or epistatic just from pedigree analysis? Or does it require further investigations?

I think I haven't explained this properly. First the confirmed, documented cases of TH in America was over a period of years, the article I mentioned was merely an example of this and a pedigree analysis of six affected calves. I am trying to work out what is going on with the British calves, so far I only have a rough estimate of the afflicted calves of 60-80%. This percentage represents a number of dams, and thus a number of calves. My point is that TH is an autosomal recessive trait, that has already been worked out. What I am trying to find out is why the hell is it not following it's expected ratio's in these British calves? My first assumption was epistasis, but the TH mutant allele is behaving in a dominant manner, which flys in the face of all previous tests and pedigree analysis that characterised it as a recessive allele. My next conclusion was that there is a loci in these British calves that affects the penetrance of the disorder so that it comes out with these observed ratio. I still haven't got any more figures at the moment, still waiting to hear back from the breeder.

I think that maybe the point is that several ribonucleotides in tRNA undergo post transcriptional modification that results in different nucleotides appearing. One is pseudouridine (psi greek symbol) and another is a single thymine ribonucleotide. As CharonY already pointed out thymine is merely a methylated form of uracil, so deduction follows that the presence of thymine is actually a result of a post-transcriptional modification, or else a deliberate incorporation, either way the result is the same. I still fail to see any controvesy whatsoever in this.

I was under the impression that although we are on BST, GMT was adjusted accordingly so that the time zones don't balls up too much. I know most countries adopted daylight saving and the equivalent of BST so I just presumed GMT followed suit, thanks for pointing it out.

Can you expand on that a little. I would also like to add that I am not referring to the American cases here, but the British ones. I have a copy of a pedigree analysis carried out on six American calves from LaPointe et al, 2000. The observed:expected ratio is way out, we're looking at incidences of 60%-80%, far too high for a single factor autosomal recessive trait. I would also like to point out that the TH locus has not been physically mapped, the only breakthrough I am aware of is the development of a marker for detection, hence the derived pedigree analysis. There is no sequence data either, very strange considering how much of the Bos taurus genome has been sequenced and uploaded to NCBI's various genebanks.

The clock isn't GMT, its GMT-1 at the moment. I'm guessing it hasn't taken into account daylight saving hours, we're currently on the summer stint so an hour ahead of normal.

This is a bit of an odd one. About 4 years ago there was a sudden spike in the prevalance of Tibial Hemimelia, a deblitating genetic condition in Shorthorn cattle in the states (USA). It was calculated to have arisen from a single sire (bull) which then spread the recessive allele to its progeny. After a while, as I said above, the prevalence spiked, most likely due to distantly related progeny encountering their cousins/grandchildren and getting the TH phenotype expressed. Anyway the ASA (American Shorthorn Association) implemented a stringent protocol for dealing with this and included a list of known carriers in its monthly magazine. Since then there has been little news of it. That's the history lesson over. Recently a bull was imported from Canada to Britain and was used to cross with a dam (a breeding hefer). Very strangely TH started to appear among the progeny, infact values were recorded at around 80% of progeny being affected by TH. That sounds closer to a dominant trait as a result of two carriers mating. The condition however has been confirmed as recessive. The bull and the hefers had samples taken that were sent away for analysis back in America where the bull was confirmed as a carrier, but a large proportion of the dams were not. I don't have the exact figures here in front of me so I can't confirm this quite yet, I've got this information directly from the cattle breeder. On a side note the carriers sometimes present mild symptoms, almost like sickle cell trait in carriers. My initial thougts were that this could be epistatic, but there has been nothing to confirm this conjecture. In fact there has been very little research into the matter. I was wondering if anyone had either a) heard anything about TH in cattle (note there is a lot of research on this in humans), or b) had any idea how the hell a recessive condition can present with an observed phentotypic ration of 4:1?! My only other guess is that an alternative allele is present in the population that either a) effects the recessive nature of the mutant allele (something I've never heard of except in cases of epistasis and co-dominance which clearly don't apply here), or that b) a new variant that was not assayed for has the same phenotypic effect so that when brought together with the original mutant allele it presents with the disease phenotype. I'm at a bit of a crossroads with this one, any ideas?

There are modified nucleotides in tRNA's that are specific and are not found in other RNA's or DNA. However IIRC they are post transcriptional modifications. It might also be worth adding that cytosine is only a methyl and an amino group away from thymine, therefore also very close to uracil. So it also has it's use in strand directed mismatch repair post DNA replication.

Luck? The pure biochemists and medical biochemists had to cover organic chem and analytical chem, thankfully biochem was sufficient for our purposes of the last two years. I think a certain amount of assumed knowledge from A-levels (16-18) is taken into account. I probably could have benefited from some organic chem lectures though because I left college 6 years ago. I honestly found that biochemistry came fairly naturally, even the basics of enzyme kinetics we covered this years wasn't too bad.

Thankfully haven't had the pleasure of organic chem, biochem however wasn't that hard surely, compared to cell signalling especially.

I'm curious as to why you don't think germ line therapy would be a feasible option, barring moral objections. I'm sure there are many scientific barriers still to overcome, but by germ line therapy surely we can eradicate only the deleterious mutations that cause these documented diseases. Selection at work again, yes it is artificial because it is us doing the work, but it is still the same work that natural selection does, just a lot more accurate (targeting one or a few alleles compared to the eradication of an entire organism). Perhaps that is a discussion for another thread though. Forgive my misunderstanding here, but Lenski and his team deliberately added citrate in excess as source of carbon, while glucose was severely depleted. Sure they did not force the colonies to develop anaerobic citrate metabolism, however they did put in place the selection pressure once the requisite mutations had occurred. I appreciate this is not the same as artificial selection when thinking about it properly, but human invoked natural selection if you will. You've hit the nail on the head there. The only issue I will raise however is that whilst beavers are selecting specific trees, this may be a behavioural characteristic individual to that organism or pedigree, they are in fact selecting against those characteristics if they cut the tree down before it reproduces. That would not be eugenics because it does not select for desirable characteristics, but against them.

I'm not sure if started out that way, but people may try to redefine it that way to justify it. True about conditions such as Tay-Sachs, this is where I think germ line therapy becomes the gold standard, the ultimate compromise? Although, as nasty as the progression of the disease is it very much highlights the danger of consanguinous marriages. But at the end of the day the incidence of T-S among high risk groups has sharply fallen since the introduction of extensive screening in the 1960's anyway. This I think highlights the importance of alternative strategies. Once you've got PGD and germline therapy working in tandem, then population specific disorders, like Tay-Sachs and Gauchers, will no longer be the problem they pose today. But of course that involves the development of germ line therapy, something I believe should be a major area of research. I suppose it is really. But how many scientists will call artificial selection eugenics when it applies to a bacterial colony, I doubt Richard Lenski considered himself to be practising eugenics when he set up his experiment for anaerobic citrate metabolism. At the end of the day artificial selection/eugenics concerning humans is considered to be abhorent by a vast majority. Objections come on both moral and scientific grounds, fair enough. But I would point out, in lieu of Lucaspa's recent post, why do we tolerate eugenics outside of our own species. Is this a false dichotomy or humans being typically hypocritical. (Please note I have not particular opinion on this, I would like to see what others think of it).

Also depends on whether it is Duchenne Muscular Dystrophy; the severe condition where no dystrophin is produced at all, or Becker Muscular Dystrophy which displays a phenotype much less severe to DMD as a result of a nonsense point mutation that results in a truncated form of the protein. Either way I doubt there is an experiment you could do for a school science fair without the aid of a molecular genetics lab. According the the Biochemist (June 08) there are no treatments for DMD as yet, although the restoration of dystrophin expression is the gold standard for therapy here.