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Hello. Hello. Can anyone hear? Mm. There's a very poorly organized from that because there's nobody here to help me out with any sort of presentation difficulty difficulties. Uh, if somebody's still on, still on the chat. Um, last thing was at 1223. Um, hello. Anyone there? Oh, perfect. How long was I out for? What was the last thing that I said? If anyone can si, I think all the med Ed people have disconnected as well. So something's going on with the presenters. Um, and I haven't got any emails. I just saw the chat just now. Uh, can anyone tell me which light I was on? Ok. We're on GW. Ok. All right. Now I'm gonna like whiz through this, aren't I? Um, hi or hand, I'm guessing here. Uh, all right. So, genetic association studies. Uh, I don't know if you guys got my book analogy but I'll say it again. And can someone keep telling me that I'm still here? So I don't come off. Uh, I'm gonna keep looking back because there's nobody else on the talk telling me anything. And the med chat is so we did that. We did the uh we go GW versus uh whole genome sequencing by guessing. So, uh so I'll probably go on to pharmacogenetics and pharmacogenomics. Uh So, study of how our genes affect the way drugs are metabolism. Uh That's about it, but not only metabolized but affected in our body. Here, we have dynamics and kinetics. Dynamics is pretty simple. Uh Think of D for dynamics. D for drugs is how the drug affects the body kinetics is how we affect the drugs. I think of kinetics and movements are how we move the drug around our body. And that includes absorption from the gut distribution around to where it needs to work. Uh metabolism of it to make sure it's inactive and then getting rid of it. Uh Not that slide. So we haven't done this. Basically, you have to just know about the 100,000 genomes project and how uh that has led to a lot of new diagnoses of a mutation which cause disease. That's about it. Uh Because of the amount of, of whole genome sequencing that was done in it. We found uh a lot of new methods which I mean a lot of new mutations which would have been missed and it included uh other types of whole uh non whole genomic sequencing, not just uh whole genomic uh uh sequencing in included GWAS and identification of common mutations. Uh He's a bit on drugs, pharmaco genetics and dynamics. Uh Am I still there? Cool. And yeah, kinetics, how it moves through our body dynamics, how the drug affects us go over that. Uh That's probably why most people didn't get this that whole question. Right. I thought I was talking during that. So here's an example of er, how genetics affects drug absorption. So I'm sure you guys got this during the lecture you were given. Uh It's a bit of a overcomplicated explanation during that, but I'll break it down for you. P glycoprotein PGP brings uh this drug digoxin and eoad out of the blood into the, into the intestine into your gut. You don't want that, you want the drug inside the bloodstream cos that's where it works. Uh And normally to do that, we account for how much of the p dryer protein we have. And that means that even though some is brought back into the lumen of the gut, most of it is in the blood, but certain uh we will get an overdose in or an underdose and uh can be bad. Pretty poor. We don't want, we don't want an overdose in a drug which is normally harmless. Similarly, distribution, we have statins which use this specific transporter O ATP 1 B1. You don't need to know the exact names for this one just and that genes can affect how our drugs get to our target tissues. And therefore they were ad drug to work. Uh We need to know that g acid used to screen for them. And therefore we can adjust doses to account for these differences in no and distribution. Uh So yeah, yeah, I'll get to the correct answer to the question. But that was after all of this, which means I was talking for a long time. Uh So uh and applications in drugs, uh we also have metabolism, metabolism is something that is very variant, not only depending on genes but on how much of different enzymes you have, et cetera. Uh alcohol is also considered a drug and there are certain differences in S and PS which cause increase or decrease of uh enzymes which metabolize alcohol into toxic versions and nontoxic. So if people get more or less drunk, it's generally because of the differences in these uh mutations for these different enzymes. And similarly, we have codeine phosphate, which is metabolized by cyp two D six. I'm actually an ultra metaboliser. So this is something that hits pretty close to home. Uh I can't have codeine because uh as an ultra rapid metabolizer that goes really fast uh and turns codeine to morphine too quickly because codeine are normally metabolized very slowly. They give quite a high dose. But without that, morphine accumulates too quickly, gets you high and then makes you die. That's how to remember it. So remember codeine phosphate and remember uh alcohol dehydroquinase. Uh everyone following you along so far here's our SBA Q. Uh So the correct answer was D because I like I said everyone should, well, I didn't say it. You guys didn't hear but you guys should read the questions really carefully. Pharmacodynamics is how the drug affects the body D for dynamics, D for drugs. Uh A limitation of G OS uh which I hopefully covered. But uh maybe you guys didn't hear is that environmental influences and epigenetics aren't useful in G USS. We're only looking at things which have already been looked at extensively before. Uh some, if one uh all of the human diseases caused by S NPS because environment epigenetic play a part and, and uh gen sequencing noncoding regions are looked at and actually the most useful because that's what we can't access from any of the other types of I froze again. Can you see me now? OK. Hopefully everyone can see me in whole genome sequencing noncoding regions are the most useful because we can't get them in any other type of genome association study. It's constantly switching in between because me was disgusting. All right now, we're looking at emerging treatments. I'll go through these really quickly because we're pretty short on time. Inborn errors and metabolism. Anything you're born with, which means that you can't make uh the correct things in your correct enzymes, uh correct substrates, anything. Uh It's a loss of function, absence of enzymes, protein substrates in your body loads of things get this down. It's a definition of inborn eryth of me. And there are loads of different diseases. Where are we gonna go with phenylketonuria and hemophilia? Because that's what you did in your lectures. Phenylketone, urea uh pretty bad. You don't want phenyl ketones. Think about diabetic ketone acidosis uh that causes your lactate to improve, cause the ph to rise loads of different things that can go bad. And all we do really is avoid phenylanine in your diet. But more importantly, the emerging treatment is give tyrosine supplements. All right, because you're not making enough tyrosine, not, not great, you need more of it. Similarly, with hemophilia, you're lacking clotting factors. Um Can everyone still hear me? Uh I hope so. Uh Factor eight deficiency of hemophilia. A factor nine deficiency of hemophilia B eight and 98 and B pretty easy. And to replace them, we use recombinant sources of basically inserting a gene into a plasmid, culturing it in uh dishes and then uh extracting the factor that we need and put them into humans artificially normally doing uh blood transfusions. Uh Now we've got chaperones. There is something that I for forgot about during my pom exam. I hope you guys don't. Chaperones are for proteins which are misfolded and that's due to loads of different mutations. An example of this is Fabris disease. Uh It's a deficiency of alpha galactosidase A specifically that's been uh not well folded and therefore you have this build up