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calls your engagement, but is your understanding and you're learning. Please be respectful. On the chat, the session will be recorded. Anything that you do will say on the uh if you're on mute yourself are turn your camera. One will be recorded on Be put into the recording as we upload on metal. If you do have a problem with that, police email us and we'll try a best to remove it. But participating this session gives us consent to put it on middle. The feedback from will be sent at the end of the session, and slides and certificates will be sent. All those attend please remove your skis, your gmail dot com or osteopenia at Outlook that come from your spam emails to receive our mailing list on, please share us a new social. We are a free, free platform, so we work on social interaction. So please, please follow us. And if you enjoy the session, feel free to post on Instagram, Twitter and Facebook and tigers and we will retreat. Retreat. You are reports to you. I will hand over to Toby Savannah and Megan today. We're doing today session embryology, congenital malformations. Um, which is K seven for college students, so thank you dot Okay, great. Thank you, Ribbons. So I'm going to start with, um embryology, you mean? Yeah, but those who had a a small question. Yes, it is being livestreamed on metal. That is an automatic recording software. So it's something new that we're doing, and we hope to transition into it in the future. Okay. Can you see my screen? Okay. Yeah. Great. Um, how everyone I'm Savannah on, do a spine of freakin easier. First session. We're going to be going over, um, embryology in this session. So in terms of what I want to cover today, I'm going to briefly go over the reproductive anatomy, especially in females, to give us a bit of a platform to work on in terms of when we're looking at fertilization and things like that. And then, uh, we will divert a bit of depth when it comes to fertilization and the processes around it on. Then move on to the basics of embryonic development as well and where things can go wrong potentially. So we start off with the female reproductive tract. Um, the past that we're most concerned about our the stuff you see on the screen here. So without with the vagina. This is the part of the practice, Jack, that receives the Penis upon intercourse on Ben, upon ejaculation, sperm is deposited. Um, the external orifice of the cervix, which is over here, if you can see my arrow and then you move upwards and you reach the uterus. The uterus has many layers. It has the endometrium, which is the animal slayer over here, which supports the growing embryo, um, and thickens during the menstrual cycle and then have them myometrium, which contracts, and then you have the perimetrium. I won't be going into too much detail about these, which have done previous, like Shires for the sake of today. Um, but we continue moving on three practice tract. We can see the ovary and the over doctor. So, during ovulation, a mature oh site is released from the ovary into the deduct. It is received by these feathery structures called Femara and fimbriated. Have many legs and have a high surface area to maximize, um, reception off the mature Lucite, the mature who site then travels through the oviduct and is there for quite a while. to maximize chances of fertilization. Um, and that's the main function of the's organs On why we're concerned with them today is because we're looking at fertilization. So if we then move on to different parts of the overdose, which is quite relevant, um, the thickest, the widest part of the bit of the we, Doctor, the widest looming on the thinnest wall is called the Ampulla, which is here. And then the wall gets thicker and the Lumen gets thinner. As you move inside and it gets more tortuous. You get the isthmus on, then finally, the intramural interstitial region of the orbit doctor, which is basically inside the uterus. Is this better over here? Um, not anyone. Tell me what? The most likely region of the ovary doctors have fertilization to occur. She's put in the chats. Please. Yeah, as rights, the Impala is correct. So the most common side of fertilization is the ampulla, which is here. So actually, almost 90% off fertilization in general happens somewhere in the over here. Over. Doctor, um, on out of that 90%. 70% of those happened in the empire. So really, most of them happen there. And if they don't happen to the over doctor and they can happen in the ovaries, or they can happen in your parents personnel cavity in the abdomen or even in your cervix, which is rare on usually these end up in miscarriages, unfortunately on in terms of implantation of your embryos. So once fertilization has occurred on you haven't our viable embryo needs to implant into the uterus where I can then receive Resource is and support from the endometrium on the most common place, and the most ideal location of implantation is the upper posterior wall of the uterine cavity. Commonly it happens elsewhere in the uterus, but this is the most ideal position. It's just it's just a fact you have to know. And if we then start doubling into fertilization, the bread and butter or fertilization is the sperm and the over. So we talk about the different spot, the different parts of the sperm. We start with the nucleus, which is basically involved in fertilization because fertilization is at it's called the fusion off the male and female nuclei on. So the nucleus of the sperm here is haploid, which means it contains 23 chromosomes and therefore has the opportunity to fertilize and become a diploid is I got upon fertilization, and then the head of the sperm also has an acrosome on top. You might remember from your A levels on the Aczone contains hydrolytic enzymes that are able to digest the outer wall off the over and therefore able to penetrate the old, um in order to then fertilize it. Um, there is a specific of chemical reaction that occurs. Call the acrosome, a reaction that involves this bet that will get into later. If you don't move further down, you have the collar off the sperm, which contains lots of mind to Kandra to give sperm the energy to swim. Because this was quite a long way, they're really, really small in size, and they have a long way to swim in the female reproductive tract and require the mighty country for energy on the also require that flagellate for locomotion to kind of wave to swim on the plasma membrane surrounding the sperm on the sides, as you can see here, is important in a reaction called the capacity Asian reaction that would talk about very shortly that is vital in terms of fertilization. But where does Mom come from? They come. They're produced in the testies, in the mail and upon ejaculation from the urethra. Um, you get semen? Semen is only 10% sperm. It's about 90% other things. Other things, I mean, alkaline fluids, mostly fractures and prostaglandins. So fructose is what the fuel is for. The sperm and prostaglandins help to work on the structures in the female reproductive system to help this burn to move along. And the reason of specified alkaline is because the motility of the sperm or how well a sperm swims depends on the pH of the surrounding area. And therefore sperm tend to work better and alkaline conditions as opposed to acidic conditions. In about 3.5 mills of semen, which is your regular ejaculation volume, you have between 200 to 600 million sperm, which is really insane to think about, which is a lot ah, lot of sperm. But you'd be surprised, you know, only like 0.1% of these firms actually make it to the over doctor, um, alive on out of these, like 50 sperm actually make it to the viable over, which is an insane statistic. But those are the odds of you being born basically, um, So I mentioned earlier most of the sperm are deposited at the external orifice off the cervix. So I was going to see after serving of the type of my bag. Sorry on all of these Burn. Can our viable in the female reproductive system for anywhere between 24 to 48 hours? So that gives you quiet a relatively wide window for them to find the over and then for fertilization to potentially occur. So I'll talk about the over, um, so, like I mentioned earlier, the's gametes have a happy new clear for fertilization. So the album has a 23 chromosome containing nucleus on the outside of a mature site, has got a collection of cells called the Corona Radiata, and this is basically like like, ah, dense collection of cells on the outside. Um, made a granulosa cells on these produce hormones, but importantly in the menstrual cycle, they make sure to become the Corpus Luteum to produce more hormones, so they're quite important in that aspect. They produce progesterone and you have a zone a polluted out, which is like this jelly like court on the inside of the coronary coronary. Really, Arte. It's kind of like a membrane that the sperm will then penetrate to get inside and that in the cytoplasm off the over you have cortical Granules. These basically vesicles containing enzymes that are really important in what's called the cortical reaction, which I get two later on. Dissension. What happened to the over is that upon ovulation, it's swept into the you trying to be and transported by silly reaction on smooth muscle contraction on bit weights, fertilization by a sperms out and whilst a sperm is viable for about 24 to 48 hours and all over his viral for about 24 hours once in the only doctor. So let's talk about what? How an embryo comes about. So if we start with the sperm that's been deposited at the exam loss off the cervix, what's gonna happen now is that the sperm is going to swim through on breach. The only doctor, hopefully, like I said, only like a very, very, very small percentage is bone will reach this place on. It's most likely going to be the ampulla because that is the most likely side of fertilization. And the way these movies firm are able to move is because, firstly, they have flagellate that tales. I have to move on. The prostaglandins in the semen are going to act on the muscles of the you trying to you. But the contract and then the contract is going to help the sperm move forward and the U 20 Walter has cilia, which helps to sweep the first bomb forward. Additionally, Easter gyn in the female reproductive tract causes the cervix to produce a very watery mucus, and this makes it a lot easier for the sweep sperm to swim through a swell. Okay, so once the sperm get get to somewhere in the over doctor before they can fertilize before they can engage in interacting with the egg, they have to undergo what's called the capacity Asian reaction, which will go into in the next slide on. Then, after the dunk, the capacity Asian reaction, they undergo the acrosome reaction, and this is kind of the point where a sperm is like right now I'm finally ready to engage in fertilization, so let's talk about what those are as well shortly, um, in terms of fertility, um, fertility off a male can be evaluated based on, um, the motility off sperm. So if you're taking ejaculation, sample off some of the mail on if after two hours, you look under the microscope and there's less than 40% of these berm that are still viable and swimming, then that would suggest that the individual may have some kind of fertility issues. Basically, that's more of a textbook number. I'm sure that's variable in real life. So let's talk about the capacity. A shin reaction. So in order for a sperm to be able to bind to over it has has to basically, um, have a bit of a shave. So every sperm has these glycoprotein on its membrane, and these have to be washed off in order for it to be able to bind to be over. So what happens is you have these green black of proteins. As you can see here on upon being in the female reproductive system, there are enzymes available around. They have to digest away these proteins, and then it becomes bear. And then now the sperm is not capacity ated on became a beloved binding to the over membrane. There's another reaction that happens here. That Silas significant is called hyperactive a shin. And what this means is that, um, basically following capacity a shin. There's a release of calcium ions on the calcium. I owns help to change the motion off the tail off the sperm from like a wave like motion to a whip like motions or more aggressive, basically. And by making more aggressive, you're helping the sperm propel forward more. Um, and you're helping it detach from the, um, over a doctor, prettily, um, where it was previously attached during capacity. A Shin hope that make sense and then now a capacity ated for sperm can now move on to the acrosome reaction. So now that the sperm is able to bind to the over because it's compacted ated, what is going to do is that it's going to release the hydrolytic enzymes in its acrosome, which is this red thing on the head here as going to release the enzymes, which you're going to break. Uh, it's going to break the connective tissue in the zone a polluted, uh, which means the sperm is that able to penetrate this layer and enter the egg. And then this health is burn. Make proper direct contact with the egg membrane itself. And finally, this basically allows the nucleus of the sperm to enter the site of plasm, as you can see here. So the purpose off the acrosome reaction is to allow the sperm to basically break through the egg membrane to allow the nucleus to get inside. Okay, And then once the sperm has kind of reached the inner egg membrane, this triggers something called the cortical reaction. So in response to an increase in, um, intracellular calcium when the sperm binds to the egg, there are some basic ALS called cortical Granules like we discussed earlier, that kind of are released from the egg by exercise Tosis and the release hydrotic enzymes. And these hydrotic enzymes make the zone a pollution very hard, which means no other sperm combined and therefore no other sperm have the potential to enter and fertilize. The advantage of this system is that it prevents something called police for me. If you have more than one sperm, potentially fertilizing and egg, that's going to cause a lot of genetic problems because that means that your finals I got is going to have more than 46 chromosomes, which is essentially not not viable at all on day suggest that up to 15% of miscarriages can be caused by police for me. So it's something that happens more often than you think it would. So once the court or Granules have been released and the sooner polluted as hardened on D, this is going to cause metabolic activation off the over. This is a fancy word of saying that the over which previously had not completed MEOWS is to, if you remember from, um, Genesis off germ cells. Now, this fusion with off the sperm and the over membranes is going to trigger completion off. MEOWS is too in the you site. And this means that the over over it's not gonna be back at 20 chromosomes and ready for fertilization. So every time, as if you remember every time a, um, immature Lucite undergoes MEOWS says it releases a poll. Our body so before this activation happens, is already one polar body floating around, which is like number one over here on Finally, when a sperm binds to the membrane and I metabolically activates the over it. Complete smears is two, and then you get a second polar body being formed, which is over here. So now we get to the main, but the climax where fertilization happens. So I've got a short video here, off under the microscope. It's off YouTube. Um, did you look very closely? We've got the two nuclei, the mail, nuclear, the sperm and the over, um, nuclear interacting and they fuse. And after the few, everything else has happened so quickly, and I just thought I'd be quite interesting to see. That's what it actually looks like. Um, so what is the point of fertilization? Why do we care about these two neatly I fusing together Well, fertilization achieves three main things. Firstly, you get establishment off the deployed number 46 chromosomes in this I got you also get establishment of the sex off this I got so x Y or ex ex on be finally metabolic activation. Like I said, um, Andi, the most important bit here for embryogenesis and embryonic development. If you remember from the video, the second they fused, they started divide almost immediately. So cleavage happens almost immediately after fusion. As you can see here, just give it another look. So it divides hundreds and hundreds of times basically on that happens really quickly. So if you can see in this microscopic images, well, if you look on the image on the left over here, this is a human use I before fertilization. It's stuck in metaphase to it hasn't quite been metabolically activated yet. And you can see the first polar body on the side if you then look at the next image on the rights. This is a newly fertilized you manu site. You can see to pull our bodies at the bottom here because you said completed MEOWS is too. And you can also see to, um, uh, nuclear. It was just before fusion my back. Sorry, you could see this is a male and the female nuclear. That's for it'll ization in a nutshell. But I think in today's actually we're concerned about what happens after fertilization because that's kind of where things have more complicated with embryology. So basically, essentially, what happens is that you get lots and lots of divisions. The case you get a rapid um, you had rapid mycotic divisions on The thing about these divisions is that they're quite different from normal. My Tosis normal mitosis. You get to daughter cells that are exactly the same size as the original daughter cell, and they're exactly identical in every way. However, in cleavage after fertilization, you have one cell that divides into two smaller cells, so they're not identically the same because actually, the half the size, Um, and that's how it's quite different on the embryos able to achieve this because it skips the growth phases of interface of my Tosis and therefore by skipping the growth phase, Uh, this means that the cell does not have enough contents for to spit into two equally size daughter cells, and therefore you get to smaller daughter cells instead, which is what this is. And you'll notice that as a cell continues to divide into smaller and smaller cells, the sooner polluted around it is maintained, and the overall size off the embryo is also maintained roughly the same. Really. Um, that's why we call this cleavage a rapid type of mycotic divisions with a lack off overall growth, because the the mask itself is not becoming bigger, but it is becoming more complicated. Basically, so initially, development proceeds at roughly one cleavage per day for the first two days, and then it accelerates a lot. So once you get to eight cells, things get a bit more complicated. There's a process called compaction that happens between eight at between the eight cell and the 16 cell stage, and what you get at the end of compaction is a structure called the Memorial. So what compassion basically is is again. It's a fancy way of saying that the cells, these little brown dots, the blast, um, ears that are on the outside off the Selma's start to become such a dear more tightly to each other via desk resumes and gap junctions. So the outside starts to become. It becomes more of an epithelium kind of thing where the outside cells start of their more to each other on the inside. Sales are still a bit more loose, but overall, when you look from the outside, it just looks like one big blobby mass. And they describe the more you allow as Iraq breathe because it looks like a raspberry. If that makes sense and this process is called compaction which is. Like I said, the development of gap chunks in the desk resumes between the's blastomere ear's. So once you have, the more you know, uh, what's gonna happen is the more you'll A then differentiates further by the next day to become a blastocyst. What happened in these two steps, essentially, is that the cells on the outside have become much more there to each other, almost like the former and epithelial A A on because they formed 70 layer. And because they have gap junctions, they allow fluids like water, and I only like sodium toe exit through them so sodium and water are going to enter through the the's. These outside last, um, ears and to the middle on make a fluid filled cavities in the middle called a blast issue. And therefore, by Day five, you have this thing called a blastocyst, which is basically a collection of cells with a fluid filled sac. In between the glasses is the one that eventually goes on to get implanted in the interests. But before that, they said, Well, we just talked about Can anyone tell me what the diagram on a what the microscopic image on a shows on the chapel. Ease. Where is the chat called your job like what is the name of the structure of showing a ask you be next. But what is a What is a look like based on based on the steps of cleavage? Yeah, it's the more you'll uh yeah, that's correct. And the reason is, the more evil is because you can see it's got lots of these globs and therefore looks a bit like a raspberry, unless we have another oversimplification. But that's exactly what it is. It's the Moria. Now, what is B? And can you tell me why it is? What it is anyone know would be is yeah, fluid filled glasses? Yeah, perfect. Exactly. Because so, as you can see here, it's got the blast, um, ears on the outside, and it's got a very fluid filled sac on the inside and therefore you can identify. This is a blastocyst around day five after fertilization. Cool. So let's talk about this last assistant. So this blastocyst, like I said before, has a layer of blossom ears on the outside. Now this layer of blasphemy is is going to divide into two types of cells, You're gonna have the trophoblast. And you're also gonna have the nurse Elmos. So the trophoblast stay on the outside. Where is the NSL mass Kind of migrant towards the inside, as you can see here. And essentially, the trophoblast is the one that gives rise to the embryonic bit off the placenta, whereas the inner cell mass gives rise to the embryo itself. So the trophoblast is more to do with, like, you know, forming the chorionic villus I etcetera where the intestine mass gives mass gives rise to the fetus itself. That is like the bare basic essentially off, um, very development. And then I cried for earlier. You still have You still have your zone A pollution from cleavage over here, and you have your blast to seal. So this is your blastocyst. But now what needs to happen is this blast. This needs to implant into the uterine lining In order for the blasts is two a day or two and implant comfortably into the uterine lining into the endometrium. It needs to get rid of the zone. A polluted Oh, the syrup, a lucid are makes the blastocyst a bit slippery and doesn't let it bind to the endometrium well, and therefore this process of getting rid of his own a pollution is called hatching. What happens in hatching is that essentially exactly what it said is kind of like an egg. Getting rid of its shell on the shell is zona pollution. So the reason this is again, like I said, is because this inner layer off blastocyst has certain proteins that help it stick to the uterine epithelium. Um, if this if this process doesn't happen, this can cause, um just a miscarriage, basically, because the embryos not going to be able to implant into the endometrium and that's his own A pollution coming out. So this is a useful diagram. I fall in the textbook, have put the name of the text book over there. Um, but it just kind of summarize is is basically so you can have a look at this in your meantime, in your own time. And now let's talk about what happens during implantation. This congenital bit complicated and it took me sometimes you understand, So I'm going to go with slower to kind of break it down and tell you exactly what's happening. Don't get scared by the different diagram. I promise I'm going to try and make it a simple as possible. So the last thing we discussed is that we've gone a trophoblast layer and we've got a inner Cellmark's Leo so innocent Marcelo is still here. It's on the inside over here, and your trophoblast layer has now divided into two. So initially you had blast, um, ears that divided into trophoblast in Selma's, and now the Trophoblast are further dividing into two types. So you have cytotrophoblast switch. Have the green cells over here, and you have sink city or trouble blasts that the purple ones over here, and you notice the look of a different as well. And this is because they have very different properties. So the sink city a trophoblast the ones over here as you can see our embedding themselves and really looking really looking to invade the endometrium, as you can see over here. So that's essentially their job is well because they want to embed themselves into the uterine cavity so that they can receive the maternal blood and maternal nutrients on. So thinks it's off a blast are really highly in rays of tissue on their able to invade their way through the endometrium by releasing hydrotic enzymes there, then able to break through connective tissue and therefore facilitate implantation. Whereas cytotrophoblast, on the other hand, they're on the outside here are more involved in forming chorionic villus I, which is the part off the fetus that will help to exchange nutrients with the maternal blood. Um, right. So now what happens now is that these things he drove a blasts are called Sink City. Oh, because they form a sink city, um which is over here and six idiom is a Latin word for saying kind of one giant mass that is like together completely bound together. And you can't really tell why it started wearing ends. So what's gonna happen is these highly invasive cells are going to form trophoblastic lacuna, and that is a fancy word for saying that they're going to form holes in the endometrium through which blood can fill in and fill in, too. So, um, I drove a plastic cell is going to form a hole in the endometrium, which allows maternal blood from the other side to enter and therefore reached the fetus. That makes sense Um, yeah. I hope that makes sense of happy to go over that again, if required. Okay, so now we've talked about the basics of the formation of the placenta off off the exchange of maternal blood to the fetus and how exactly that comes about. But when the embryo is in the uterus and implanted, it needs some kind of support. It can't. It's not viable on zone. Yes, the over it has. The, um has lots of nutrients in it, but that's only viable for about five days. And therefore, after five days of these external support, external resource is so the human, the maternal and Dmitriev actually is going to differentiate into death A Jew, uh, which is the kind of endometrium that is rich in glycogen and rich in lipids and therefore was able to support the growth of the embryo and therefore, the formation off this decidua, or this glycogen leopard rich endometrium, is called a dexa jewelry action. So the connective tissue cells in the endometrium will differentiate into large polygonal cells. It's not very clear on this microscopic image, but if you google it, you'll find pictures on and they contain lots of blockage in Olympics that earlier to facilitate and support the growth off on the embryo. And this is to make sure the embryos viable. Now, the disease, You actually have three different parts. Um, you may or may not have heard about this, and I'm going to go over it very briefly. And this is because the decision basically supports the entirety of the fetus, not just one part of it. What I mean by that is you have the residual bizarre lis, which is this bit over here, and this supports the chorionic villus I off the fetus. You don't have the decision Capital R s, which is over here at the bottom, and this supports the fetus itself. And then you have the decision of parasitologist, which is on top over here. And this supplies the the cavity of the uterus that is not occupied for by the fetus. The non features bits off the endometrium. That makes sense. Um, you usually don't even know that much detail, but I just thought I'd mention anyway, for context. Great. So if you remember again for lier we had a trophoblast and we had our in a cell mass, so what we've talked about. What happens? The trophoblast in differentiating decided of a blast and things you know, travel blasts What happens to the NSL Mass? So this, as you can see here, is a wonder developed embryo basically because he those blobs of in a cell mass in the middle, What's gonna happen now? It is going to differentiate the form what we call a bilobular disk bile Um, in a disk means it's forming a like a layer off two different cells. So this single layer off in our PSA last is going to differentiate into epi blast and hypoblast just below it. So these are in cells are happy plastic cells on the blue ones, the hyperplastic cells. And these will continue to differentiate LC as well see later to become different parts off the embryo on the, um chorion. So before we talk about what happens to the epi blast and fiber ah, hypoblast, which I would definitely get to, we need to touch upon gas relation. Gas relation essentially is just the like. It's kind of a very important induction induction event into inducing the body access, so the fetus needs to know where it's head is and where it's toes are. And that's the point of gas today, shin. So what happens is that this thing called Henson's note for the primitive note emerges in the middle of the fetus. This is a top down view off the embryo on. Then a line emerges from this note and goes from cranial to Kordell. So it goes from up to down, and it forms a line called the Primitive Streak. And this is the most significant signal off gas relation and the most significant signal off embryonic development. Basically, because it forms the body access, if you look at a child, is kind of what I'm getting at. You have the primitive node in the middle, and it's moving down words from cranial to coddle to form the body access Cool that is the basis of gas station. But essentially, what happens to the abbey blast on high blood blast? Is that the further differentiate into what's called a trial am in a disk? So here you had a bilobular disc, but now the bile amorous is going to become a trial am in a disk. So how does this happen? Well, essentially, your baby blastic Cellstory. I put the label in the wrong area for the labels meant to be here. So your epi blastic cells will migrate through the primitive streak so they'll come through the primitive week upwards on. They are going to form a layer between the epi blast on the hyper blast called the me so dumb and I think of me as a dumb em for middle. And me Saddam is the middle a on that's how I remember it. So the epi blastic cells with migrants through the promoters streak and former intermediate cell layer called the me Saddam. And because of the Ms Adams in the middle over here. And then the Apidra last itself will again some more rapid basset cells will migrate from the primitive streak on go downwards to form a on there kind of merge with the Hypo blast acceptable downwards and from the endo damage clear, which is down below, and the remaining cells will go on top to form the acted um So all of your embryonic tissue essentially originates from your epi blast. Every blast will go to from the ms a derm. Well, then bind with the hyperplastic become the endo dumb, and then the remaining tissue will go on top to become active. Um, so it's outer, middle, inner, if that makes sense. So this form is your trial, Um, in a disk. Great. So now you have the basic of your embryonic tissue. But in order for your embryo to live and to thrive, it needs to have a nervous system. It needs to be able to send signals from it, needs to have a brain first thing needs to have a spinal cord. It needs to have nerves on this process off. Induction off This nervous system is called new relation. In order to have a nervous system, your body, your embryonic body first needs to generate in notochord. So in order, cord is basically a rod like structure between the Actos dumb on the end of, um and essential for the development off the nervous system. So what's happening here is that you're noticing it essentially is made of me. So dermatis you. The note card is miss a dumb in nature on What is going to do is that it's going to cause the primary inductive event. The primary inductive event is where this piece off, Miss a dumb this rod is going to signal upwards to the acted, um above it to differentiate into new rooted issue because the accident is above the me. So dumb. The exit, um, is going to respond to these signals and therefore, the tissue that is directly above the Notre card is going to differentiate into neural type tissue. So what, you get our neuro cells basically in this area, So just talk about new relations specifically, and the formation of the spinal cord and the brain. All you know essentially need to know is that this new oral tissue that is formed on the accident, um, essentially includes the newer plate, which is these flat flaps. And you can see it also includes in noodle groove that you can see that running down the center over here. And what's gonna happen is that as the embryo progresses, this group is going to become longer and narrower, and these flaps were kind of going to close over each other and form a tube. If that makes sense, and once you form the tube, you're going to get, um, once informed the tube, ignore the little dots over here, but one C from the tube. You can see that the top of the tube and the bottom of the duke have not closed. They're still open. And that's what's called the neuropathy. Your pores. So the top, the top opened that is called the anterior in Europe or and the bottom open bit is called a post here in Europe, or you don't really have a function. However, if they failed to close, they can cause problems. So if your anterior and your portal feels to close, you get things like this, which is on and carefully, which means you don't really get development of the brain in a person. And if the bottom off the posterior a new report, the bottom whole doesn't close. You get things like spinal bifida, which we'll talk about in a bit. That's new relations in a nutshell. But you also need to importantly, know about new request cells have really talked about these, but basically, when the noodle plate kind, the flaps kind of close to form the tube. Once they close, you can see these little cells and green called the noodle crust cells that are remaining and these new cars sell a really important in that they form many other structures in the embryo, for example, they form your peripheral nervous system. They form short cells and adrenal medulla onda. Other things that you can read here, and I would just memorize this list. Essentially, Um, and then, obviously the crux off new relations is that it depends on certain proteins. Like I said, there's a lot of signalling happening here. Something has a signal to something to differentiate into a certain kind of cell. And what facilitates the signaling patterns are newly induction proteins. You don't need to know still signaling patterns for any of these. No one will ever ask you about these, you see to know the names. So, for example, you have the Wnt family of proteins that are involved in the induction off differentiation off the MS A Derm and Xeloda, you have sonic hedgehog proteins that are really, really important in different See a shin of the note, a card on the notochord signaling to form the neural tube, and then your the T G of beater family of proteins and the bone morphogenetic proteins that are just involved in the entire process. Basically, if you just know these names and roughly where they interact in the process, that that'll be good enough. Another thing to memorize is derivatives off different embryonic tissue. So, for example, we know the acted, um So the Actonel has lowered the derivatives. And the way I remember the drugs act, um is that it differentiates into things that are sensory and keep you in touch with the outside world. So what I mean by that is, for example, if you look at the left here, but I mean things keep you in touch with the outside world. I mean, like epidemics, because it's skin's. We use that to touch your nails. Um, your sebaceous glands are all part off your skin and things that help you keep in touch on D. Things that are sensory of things like your eyes or your nervous system or your teeth or your or your neurons. Um, and therefore that's how I kind of remember the drug tips off the actual job. So I would again just memorize this stuff. Basically, I don't have a list of everything. All the drive to school, I thought was quite pointless because you can find anywhere on the Internet. I I thought, This is just one way I used to remember actually relatives great. So if you remember earlier, I said, If your neural tube doesn't close properly, it can cause problems. And one of the most common neural tube defects. In fact, the most common your tube defect. It's called spina bifida. Spina bifida is basically, like I said, that is called the failure off closure off the noodle groove, as you can see here. So if you look at this bit off the spine, you can see that here. There's a bit of skin over this area of the spine, but this little blob here has no skin over. It has no tissue that's managed to grow over it and basically has enclosed on D. It's important to note that that is, that doesn't necessarily always cause cause spinal cord problems. In fact, most times your spinal cord is mostly intact. The way you can recognize this in Children or in people is if you look at that back, usually in the lumber or sacred regions, you can see a collection of fat in that area or tuft of hair, Um, or even a dimple in their skin. And that kind of is a usual clinical indicator that there might be spina bifida going on. It can cause disability is even in tract. Is your spinal cord things like neurological problems a zit can imagine? And because it usually happens in the lumber or sacred region down your spine, you can get problems with like, yeah, with your bladder function with just lower limb. Perilous is because that's what your lower spinal cord is usually responsible for. So how do you prevent spinal bifida from happening? This is one of the most important supplements women take when they're trying to conceive. So when they're trying to conceive, every woman all women are advised to take. A 0.4 mg does off folic acid every day, starting at least one month prior to conception, and this is to make sure that they have enough folic acid in them to facilitate the proper differentiation off the new tube. On, as you can imagine, like I just said fall, it is really important in your it information because it kind of acts as a cofactor for enzymes involved in DNA, a synthesis on some women particularly, are at higher risk off having spinal bifida and their Children. And these women are usually those with co morbidities, like type two diabetes or obesity, or are on anti epileptic medication. And these women are advised to take a much higher dose of folic acid. So 5 mg as opposed to 0.4 mg, got a small SBA. Um, what? We would launch, please. So just just pull. Yeah, Great. This is just a a bit of a factual question. Um, no pressure. If you don't know it, I wouldn't have known it. Um, the ponds and terrible, um, originate from which of the following structures. It's gonna wait about 25 seconds for this one, actually. Okay, so I see a bit of a bit of a splitting B and C between dying. Careful on and medicine. Careful on. Um, very good try and force of the answers, Actually. Deeds met, and careful on on. Unfortunately, this is just one of the things you have to learn. I've made this diagram because hopefully it's easier for you to learn it. So this is a neural tube, essentially in the very beginning, and with time, it becomes more and more complicated. So the orange bit is your four brain and then the yellow, but your midbrain and the green with your hindbrain and each of them continue to differentiate into their own bets to finally, you look at this in your own time. But you please, um, he finally gets different parts of your brain and your central nervous system, as you can see over here. Great. For the sake of time, I'm going quickly brush over this But Zometa Genesis essentially is when you have pieces off me so dumb in your embryo that form these little bold of tissue along the spinal cord kind of area, as you can see here and these are important because they differentiate into important by products. So so mites differentiate into sclerotome, myotome and dermato, and to sclerotome basically gives you connective tissue like cartilage in your skeleton. Myotome gives you muscle and dot um gives you a connective tissue that is involved in the skin and the dumbest. So these are important derivative Zof the so mites and finally, working things go wrong and embryology where actually it could happen any time. Embryology is a very susceptible period on D. But the main three factors you have to consider is that territory gee is important. Consider, based on when the toxin has come into contact, how much of the toxin is coming to contact and how well the embryo itself is genetically able to deal with the docks in. For example, I'm going quickly, fast this. If you look at rubella infection, it's extremely toxic on D. In the 1st 12 weeks of conception, if the mother is exposed to rubella infection, there's 100% chance that her child will have congenital abnormalities and a 20% chance that that the one in five chance that hurts you just have a spontaneous abortion. Unfortunately, therefore, teratology is really important in that you have to make sure that the mother isn't given drugs or exposed six infections that can be potentially extremely toxic like this. Uh, I you could do this embryo was good, this MCQ, but for the sake of time, I won't do it. Um, so this is just asking you which of the following options are from the ms so Damn theanti. So is it real cortex? I made this question to be a bit confusing because sometimes it's difficult to remember which. But it's a seasonal medulla. And which bit is the cortex and which comes from what? And this sp just emphasize that is really important, that you go back and learn all the derivatives a robotic tissue, because it does come up in exams. And it's quite important. Um, so, yeah, I hope that helps. That's in my presentation. If you have any questions at all, feel free to email. Those are message Mean the chaps, Um, but yeah. Thanks. I'm now possible into Meghan. Yeah, so just a quick update. I just want to remind Megan and Toby if you just slightly hurry, appear your presentation toe. Um, in the meantime, while Mekinist sharing her slides, please do join our mailing list. And always remember that every Monday after the case, we always do a revision session, and we always going to be doing that through the year. So join us there. Thank you so much. So I know that was really, really comprehensive. Thank you so much. I'm just going to share my screen. I would be You can see that. Yep. But it ain't great. So high, everyone For those of you that don't know me, I'm Megan on one of the pre completes. So today, what I'm going to be going through is congenital abnormalities and antenatal screening. But I'll just get straight on with it. So for those of you and card, if I've just done a little table here, if you're in reference as to what I'll be covering today and if you're not from started, don't worry too much about this little. So I'm going to start off with congenital abnormalities. So I'm going to start off with some definitions. So when you're talking about congenital abnormality is it's really important to get the terms involved in this topic in your head straight away. So I'm going to show you a definition, and then I want you all to type in. The chat is quickly as you can, what term I'm defining. So what is a structural functional or metabolic disorder? President Birth? What is that describing? Can anyone pop it in the chapped for me? What term? But defect? Yeah, brilliant. Well, don't guess it's amazing. Yep. So, yeah, a birth defect or a congenital malformation so congenital just refers to any condition that is detected at birth or, if it wasn't detected about, it's believed, have been present from birth. So a congenital malformation. It basically includes any conditions that president birth, whether they're inherited, that caused by chromosome, no abnormalities or caused by environmental factors. And I'll be going over shortly some of the different causes of birth defects and congenital malformations. But just to clarify, because that that you can get confused. Sometimes these two terms birth defect in congenital malformation, they're interchangeable. So our next definition so any variation from the normal physical structure structure due to environmental and genetic factors acting other, independent, new together because during the formation of structures are your gonna genesis to in the organs are forming on. It's mostly during the third to eight weeks of gestation. Any ideas what that is? What's that defining malformation, yet brilliant yet was? See if that's a malformation, So I've highlighted it there. The main thing that you need to know is it's during the formation of a structure, so as the as the terms, yes, it's a malformation. It's just forming incorrectly. So next definition. So a mechanical force that causes changes in the physical structure of the fetus on it occurs over a prolonged period of time. Can anyone tell me that definition? Defamation. Brilliant, yet well done. So yet that is a definition eso deformation of a ski as it says they're. They're alterations in the shape of a part of a fetus. It's due to an external course. They're usually reversible once that extended course has been removed or because it's due to a mechanical force if the opposing force so forth happening in the opposite direction because that can also correct the damage. So I like to think of this as a bit like what you would use if you're using a hammer. So if you hit a hammer against the surface, you're gonna deformity. But then, if you put forth in the opposite direction, it will usually change your back. Brilliant. So move onto the next one, a destructive force that alters pre existing structures, saying we'll know what that is. Pop it in the chat. Nice and quickly disruption. Brilliant, yet well done. Yes, that is a disruption. Eso disruptions are not the same as deformation A Z. They're due to the just more of a destruction of approval see normally forming organs on organs forming normally. And then all of a sudden, this destruction comes about. These tend to be more severe than definitions, and because they're more severe, they often cause Selda on. Therefore, they're less likely to be reversible. And so I just want to recap that point. So definitions in disruptions their results of mechanical force is that are affecting previously normally developing tissue, which causes it then to know begin to not develop properly. Whereas a malformation is an intrinsic primary problem in the formation of the tissue hope that make sense. So our next definition. So when a primary anomaly causes an additional defect, is they will know what that's defining. Yeah, well done. Brilliant. Yes, the answer's sequence Well done. Move on to our next one just the time. So a pattern of malformations occurring together considered to have a specific common cause where diagnosis can be raid, the risk of recurrence is known. Yep, well done. That's a syndrome well done, everyone, that's it's injuring. That's really good. Next, a recognized pattern of malformations where the initiating cause has not been identified. Any ideas of eyes? Association? Yes, you guys doing really well. Yet that's an association, says the name suggests the symptoms that they're kind of little collections of symptoms that can come together and be associated together. That's how I remember it. But you don't necessarily know the cause. You can't give a patient of risk of recurrence or anything like that. And our last one son has already alluded to it. Anything Capel capable of disrupting embryonic or fetal development and producing or defects or congenital malformations? Teratogen See yet, Well, don't have one that said that that's really good. Brilliant. So just to illustrate the point, I'm just gonna give you a few examples. So starting on the left is a conditional club foot, so Comfort describes a foot, which is twisted so that the fault the sole of the foot can't be faced flat on the ground. Um, it's usually a result of low amniotic fluids on that causes a compression of the fetus is for from the mother's organs of the mothers, organs begin to press on the feet of the fetus. So based on that information, can anyone tell me what type of birth defect is? What definition would use defamation yet well done, yet. So that's the definition. Is the reason why that's the definition is because the fetuses feet of being compressed by the mothers organs on go the feet aren't being destroyed. Like you get in a disruption. They're just changing shape. And actually, once the fetus is born, he generally manipulate their feet or you can use the cost is well after birth. That can help to reverse it. So then, if we go over total, I've just revealed it. Now, if we go over to the right, we got amniotic bands and drones. This occurs when there is a tearing or rupture of the Ambien, and all the Ambien is is basically in a membrane of the minority cavity on that causes little parts of it to come off. And they can, as you can see, that they can kind of try around different parts of the fetus, particularly the fingers, the toes, the ankles, etcetera. So this is a disruption, and that's because you haven't external force that is causing destruction to a normally forming organs. So in this case, the hand it's causing destruction to them when they were forming, forming normally. Ondas, you can see here this can cause a bit of a constriction, and that's really hard to correct without surgery. And then finally, in the center, the side. We have oligohydramnios iss. So this is basically just describing a deficiency of an aortic fluid. So can anyone tell me what definition you would use for this one? People put in the shop sequence yet was on you guys on it. See? Yet this is the sequence because your primary primary anomaly is the lack of the amniotic fluid on. Because of that primary anomaly, you can get additional defects. So if you have low amniotic fluid, you have a preterm birth. You could have fetal growth restriction because if there's less amniotic fluid, that's there, space for the fetus to grow. And you can also cause abnormal presentation or orientation of the features that, but because if there's not enough amniotic food, the fetus is it going to be able to turn around as it should? Well, guys, I think you've got those in your head pretty well with them, so I'm going to now just talk through the quick five main causes of birth defects. So starting off with chromosome where abnormalities I will be talking about more the shortly. But this is when you have kind of larger problems with the crime zones. Then you can have single gene defect. This accounts for about 8% of birth defects on these can be inherited from parent, and they can show you kind of Mandela and inheritance patterns, or December or old, so more dominant or December recessive things like that. But also they can be spontaneous as well on. That's when you have your mutated base in Exon or a coating region of the DNA. Then you have some environmental factors have listed a few here on that accounts for about 7 to 10% of birth defects. Um, one thing that you guys really should know is that all drugs should be avoided if possible during the first trimester of pregnancy, unless the expected benefit of the drug to the mother outweighs the rest of fetus. And that is just simply because a someone has had a lot of development, because during that first trimester, that's when most of the development of the embryo is occurring. So understandably, due to ethical issues, we can't test all these drugs on pregnant women or pregnant animals. So we want to avoid those drugs, and just so they don't have any to write a cardiogenic effects, then our next thing is Katarina is multifactorial, a zoo course with birth defects. So this counselor, about 20 to 25% off birth defects. And as the name suggests, this is just when there's multiple causes of place, a genetic and environmental. And then the most important thing that you guys need to know is that the major cause of birth defects is an unknown cause, or an unknown etiology on that accounts for about 50 to 60% of breath defects on. That's just because over time scientists will find more chemicals and other factors that could be added to our list of tacticians on. However, at the current time, we haven't identified the ball. So unidentified course is still the most common reason for a bath effect. So then focusing on the environmental causes of those birth defects which I said accounted for about 7 to 10% of them congenital malformations, our our environmental causes. So, for example, traditions, um so teratogen ESIs. It has three principles. Teratogenesis is the process in which direction to Raptiva cardiogenic sub substance causes that birth defect in the fetus. So it's the kind of process of which the damage takes place. Form a direction. So I included some traction examples before, So things like drugs. I'm sure we've all heard of the little mild and that causing birth defects, alcohol cameras, well, German measles. See MV cytomegalovirus Ionizing radiation is well, there's lots of different directions out there, and knowing a few for your exams will be really helpful, but as solid, looted. Two. There's three main principles of tractor genesis which control how how we given effect the direction has on the embryo basically the first mean dosage. So understandably, if you have more of a teratogen president more of that harmful substance, then you're gonna have a higher risk of having a birth defect. Then you got the genotype of the embryos of even if you have the same dose of a tourist in same length of time of the exposure, some embryos or just sadly, be a higher risk of malformations. And then finally, you've got the timing on the length of the exposure to the traction. So understandably, the longer a period that embryo is exposed to attracted in the higher the risk of a malformation. But another really important term, you guys know is the critical period. Onda Lot of trust in we'll have the West effects during the critical period on the critical period is usually from the findings you from the end of the second week of gestation to the end of the night week on as a Honda talked about. That's mainly when fetal development is occurring after you get past that point. A lot of the fetal development is just the the feet is getting bigger. Basically, most of the stuff at the gas relation no relation of forming all the structures takes place in the early days. So if you have a teratogen during the critical period earlier on in development, then you're more likely to have damage as those structures of forming and therefore birth defects or, more likely to occur. So now I'm going to be going through chromosomal abnormalities, so a little bit of a recap of chromosome a anatomy. I don't want to labor the point too much, so we know that chromosomes are basically just one really condensed molecule. DNA, which is only visible when the cells dividing. So when the mitosis meiosis when the cells in interphase when it's not dividing. So we know mitosis makes up some of the cell cycle, but Interphase makes up the rest of it. Wedding into phase. The The DNA is just diffuse in the cellars, cramped in it's it's not condensed into these crimson's to reading point. Important boys you need about No about Crimson's Artemus team is are repetitive. Basic ones is basically the act as a bit of a cup on the end of the chromosomes on this insures that DNA replication basically takes place right up until the end of the coding regions of DNA. Every time you replicate yourselves a little bit, DNA is lost, a the end of at the end of it. So you want to make sure that you're just losing these kind of useless repetitive. Basically, it is rather than coding information that's coating for proteins that you need in your body. And what least, um, is also do is they insure that yourselves congesting wish between theand of a crime zone where there's this repetitive, basically, does that say, or if the chromosome has become broken. It needs to be able to distinguish between them when it's a broken crimes own and when it's just a normal crimes own. And it's got these teen, um, is on the end, which showed that's the natural into the chromosome. The other important part you need to know about crime zones is the Centrum. It's this is also mainly made up of repetitive basic princes. Basically on this is the site where to sister committed join together when this other is dividing on. And that's really essential, for my toast is in my office. I like to remember that says, I've, um highlighted on this side as centromere. It begins of Central, which is the same central, and telomeres. It's on the tail end of a Zylet. Remember, it also begins to taste, so it's a the end of the prednisone. Then, um, looking again at the chromosome structure, you've got two arms. Generally of a cream is only on the shorter the P arm along on the Q Q. Um, on the short term is the P R. Bond I remember. That is, it's pretty. It's It's another way of saying small on, but why? It's the PR. So then I'm going to quickly recap over my OSIs. So my OSIs consists of two successive cell divisions which produces are Ford or two cells on gets really important to remember that when you genesis occurs So when you're generating female gamete by my assess, only one of those four daughter cells becomes the mature. You cite that them goes on to undergo fertilization, the others for much smaller polibar reason. They have less organelles and less side pleasant, so they're not using as many resources. The femur hasn't had to have made many organize inside cousin for them, so it's saving your resources. So my sister has two main functions. Can anyone name them for me? Can you put in the chat? Why? Why do we have my OSIs? Why is it important? Why don't we just use my toast is for everything Variation. Brilliant. Yet any other ideas keep coming. Okay, good. Yeah. So it's firstly to reduce the chromosome number. So gamete need to have 23 chromosomes in humans robin and 46 that you'd find in a diploid cell on as a leader, as you guys, I said there is to make sure that the gummies are genetically you need so as a little bit of a recap, I don't want to live with a point too much s o in metaphase one's office at my house is one sorry out first division during prophase. So your homologous crimes own so chromosomes of the same number from both your mother and your father. They line up at the center, there center of the cell and they undergo genetic recombination is that's basically when a crossing over takes place between the homologous crimes owns eso that the two sisters princes are no longer identical. Then message days lines up at the equator and I rub This is M for midline. But then in anaphase that Malaga scream zones of randomly pulled to the post polls. So in one, so you might get the paternal crimes and one in the maternal chromosome too, but on the other. So you get the opposite. So you're switching up which of the maternal and paternal to go get it So interior phase inside to kinesis. That's when the doctor cells are forming. They're distinct UTI and spitting off into different cells. Then in my OSIs to this is quite similar to the process of my Tosis eso in Prophase and metaphase they spend. If I was there, attached to the Centrum is and the sister chromatid line up in the middle on. Then in Anaphase, they go away, they move away from the center, moved to the opposite poles on then telophase those nuclear envelopes reform and you form your four happily door cells. I've written there a swell I won't labor. The point is, I've just talked about it. But those are the important parts of my OSIs that you guys don't need to remember for exams. So remember crossing over is improving one and, um, in mess phase two. That's when the new site is arrested. Whilst it's waiting for a for sperm to me first lies on. Once a personalization has occurred, Then the rest of my OSIs is completed. So in terms of chromosome abnormalities, there's two types of creams, um, abnormalities, the first being new miracle. So this is, as the name suggests, when the number of chromosomes or a particular chromosome isn't is abnormal, is not correct on, so there are few men tights, so try zone. Lee is basically the presence of an extra chromosome. As you can see from this image s so you have three copies of that chromosome instead of two on. But what happens is, if you got that third copy, you have to you have to much genetic information. Too many too much genetic information coding for the same protein so often. If you ever tries, only, you produce too many proteins that coded for from that chromosome and you just getting over production of those That's generally easiest, easier to survive than, say, a monosomic, which is another type, which is where you have an absence of a chromosome. If you imagine if you only have one chromosome rather than two, you're gonna have to little protein made from their genes that coded for on that cream zone. And that's the hardest and survive because you have less of you're not gonna have enough protein to do with your body. Live functions that you need your proteins and your enzymes for so that's why you often have more tries, um, ease than we do more mesalamines. You can also have Poly Poly Ploidy um, which is basically the presence of a whole extra set of chromosomes that all of your 23 times and you can have a complete other other set. The most common that you'll come across is triploidy, which is basically when you have 33 sets of chromosomes on police. For me, that's a hard talked about is a possible cause for that so often extra spoon gets in, you get a whole another set off chromosomes into that front of. So if the cell does have triploidy, it will spontaneously abort on bats. Do two issues with cell division. You know that's That's I go just isn't going to be viable. Um, so I've talked about how normal body cells 4 to 6 g owns, and that's deployed. Where's our gamut of 23? If a cell has a normal amount of chromosomes in it, it's called, um, Ploidy. But if it has one of these abnormalities, then it's gotten any pretty. And as a set, those include tries only monosomy. Intra pretty other type of chromosome abnormality is a structural abnormality. So this is when the structure of a particular chromosome is abnormal, so you might have the right number, but the structures incorrect. So this conclude deletions of bases duplications, translocation, xyz another major one that you want to know if your exams of which there are two types of translocation that already high yield. So a cyclical translocation is basically when fragments or swaps between chromosomes when there's two broken crime is owns on. But there's no loss of genetic material in that swamping, however, where these breaks form. If there is a gene that's formed across that break, you can imagine some of the bases within that gene will stay on one prednisone, but the other will be transferred so that can cause the protein coded for by that gene to not work. Um, and then that can cause, uh, various birth defects. Another one is Robert Sony in Translocation. So this occurs on ACROCENTRIC. Crimson said. Crimes is a very short PR, very short peel. And what happens is those p arms are often lost cause they're so short on Dean's AARP ODed, for on that p arm are lost, and that can also cause birth defects. So, as I said, um, any parties are the are new miracle abnormalities in the number of crimes owns. When you have the wrong, um, wrong number of crimes ends into south and that these these abnormalities arised you to something called non dysfunction, which has shown a picture on this side. So none destruction is basically where one or more pairs off homologous chromosomes or sister committed don't separate correctly during my OSIs. So either when the homologous chromosomes don't separate probably in my roses one or the sister promises don't separate properly and my sister on, As you can see from this image, this results in abnormal distributions of chromosomes between the four door cells that made so some of the gamete that created end up with 012 sets of chromosomes s. So therefore, when they're first lies and they get another set from the sperm or the egg, you're then getting between 1 to 3 copies of homologous chromosome. And that's how we'll try Zomig Zone or my nose only is that right? Arise. So what I'm gonna go through now is some of the common try. So knees and monosomy is and conditions that you'll see on be tested for exams. On what? I'm gonna go through some of the high yield features in each of those. So starting off we're down syndrome, So the carry type of down syndrome is 47 xx test. Would you want it? You can also be X y. I've just done it was x X is a girl, but it could be ex wife is love it if it was am male baby as well. So 47 just represents number of chromosomes, so we would normally have 46. There's an extra one on the plus 21 just told you where that extra cortisone is basically, So we've got an extra chromosome 21. Now Down Syndrome is the most common tries only you'll get, and that's have just explained often occurs due to non destruction during my OSIs Onda risk of a baby being born with Down Syndrome on any of our other abnormalities increases with maternal age. And that's just because the process is that happened in cell division on as they aren't as regulated as well as we increase in ages. So could anymore pop in the chapped for me, any features, you know, if you were to see a young baby with down syndrome, can anyone name any of the features you would expect to see your problem? in the chapped low PSA is brilliant. Any others? That's it. It's under. Got some of those? Yeah, Don't lose yet. Single palm A crease. Brilliant. Yeah, sure, Yeah. Pretty. And, yeah, you guys have come up with a lot of good ideas yet. So these air the main features that you need to know what I've done it on these lies, Guys, just for the next few side is the main ones that come up in exams the buzz words that you often see I've highlighted in that orange yellow color. So those are the really high yield statements that you want to learn. So you have increased a nuclear translucency. This's basically a measurement off kind of gap in the fetuses neck that's seen on ultrasound on def. That gap is increased when the the ultrasound is performed that consider test that the baby has downs and drone on that. The anti The nuchal translucency is usually measured around 12 weeks, then dancing. They're babies are from quite fluffy, fluffy on the brush field spots. These are basically small, white or grayish brown spots that you see on the preference of the iris. I think even just about make it out in this image Here. Um, single problem. A crease low psa is You guys have said brilliant. Another one I will highlight is epic camping. Folds of these are basically a skin mole that comes over the upper eyelid on that covers the in a corner of the eye that's quite characteristic of down syndrome, and I'll let you read the rest in your own time. But you guys came up with lots of good ideas. So we're done dancing joins mainly diagnosed in three ways. So, as I said before, it could be a structural finding on ultrasounds, things that you're increased New nuchal translucency. It can come from antenatal spinning, but tests s O. U often find that people that are going to have a baby with down syndrome have an elevated hate CD inhibit a and they also have decreased maternal serum alpha feta fetoprotein. So repeat that again. So you have elevated hate CD and inhibit A. They have decreased maternal from a serum. Sorry alpha feta party on the other way that you can download diagnose down syndrome is that births? They may have congenital defects that just heart defects or their facial appearance of breath can also be suggestive of down syndrome. So our next one is trisomy 18, which is upward syndrome. This is theseventies most common trees only. Can anyone pop in the trap? Any features? Um, any features off presently? 18 that, you know, market about invert Brady in anything else. Pinched hands. Brilliant. Yet you got to come out with a graduate, yet? Well done. So the main ones that you guys need to remember our crunched hands with overlapping fingers on so often this is where the index and the fifth fingers are overriding the third and the fourth. So it's kind of is kind of like that. That's not the best way to describe it, But it's kind of like that. Um, then, yeah, a major one you guys picked out, which has shown in the voter. Here's a locker bottom feet on. So I can remember. This is it looks like the bottom of a rocking chair on the way that I remember that this is linked to try Zomig. 18. Is that you kind of not to. Stereotype. Do you think of rocking chairs is being a sign of older adult hoods on adulthood begins at the age of 18. Therefore, um, rocker bottoms feet is associated with your eyes, only 18. I hope that makes sense. That was the way I always used to remember it. Um, another important thing that you guys need to know is interview trying. Growth restriction on that can cause the fetus to be really small when it's in the you dress. So next one is a Talis Syndrome trisomy 13. Any ideas on any of the features for this one? My cookie if the, uh, productively, Yeah, I think someone's a cleft lip is Well, yeah, that's really good. Yet I think you guys have got the main ones well done. So, yeah, Paul is actually is they're having more than five fingers, cleft lip in palate. So that's when there's a gap or split in the upper left lip or the roof of the mouth. So the palate there's a gap in it. As you can see in this image that's quite characteristic of charged only 13, um, on. But, um, I think you guys said as well, but, uh, you know, president carefully, which is really good. One thing that you probably want to know and understand is that Trisomy 13 is more severe than trisomy 18 on Trisomy 18 is untreated. Me 13 most of it, and trisomy 21. And that's because, and Trisomy 13 has the largest crimes own on. But then it's 18. It's 21 on because the creams there's a larger intuitively their coding for more proteins, you're gonna have more severe effects, so try is only 13 has heart side. Be higher rates of miscarriages and still west on down. Sometimes these babies just can't survive with those levels of birth defects. So this is actually quite a recognition. It's the next one are only viable monosomy that we have his Turness in General Monosomy X Day one only features of tennis and drinking you quickly but, um, in the trap Web night. Brilliant infertility Web neck short yet short weapon. Yeah, you guys doing really well? Well done. So, yeah, your main features is it's a female because it's mother's only X Web neck. You're often hear shield shape, chest or broad chest, often as well. Short stature and a memory up. A swell Infertility is another important one, and that's because these women yeah or insight. Oh, you can use IVF to help these women have Children. Now I have a question for you. Sex chromosome, A new protease. So differences in our crimes, their numbers generally mold or they're not water. So many parties, so are kind of chromosomes. 12, 22. There's a couple of reasons Why does anyone know why? So why Why are are, um, X and Y chromosome abnormalities? Why are they more mild than our, um, on number two? Chromosome abnormalities? Yeah, brilliant. Yet except inactivation. Yet that's one. Yeah. Brilliant. Does anyone know the other one? It's quite It's quite a gym worry. Yeah, okay, yeah. So you guys said one excrement own is partially and activated anyway. A said before you don't produce too much of protein on because males only get one extreme zone anyway, if you're a female, one of your X chromosomes gets turned off anyway, and it gets packaged into a small bowl, which is called a bar body. Um, the other reason why it's generally mild, uh, is because what the white chromosome is quite small and head. It's once again because it's more it doesn't contain as many genes, so our last, um, it's injuring. That I'm going to go through is kind of a syndrome. Any features for this one? Anyone know any reaches of this in of the syndrome Open in the job? Gonna Comast? Yeah. Yeah, I get to to brilliant yet. Well, that everybody that's really good. So yeah, So the main features that you need to know a gynecomastia. So breast development in males a tall generally they have less model less muscle in this body hair, they can have infertility issues generally, if you're just trying to generally remember this condition, just remember that people with crime felt syndrome have a more feminine appearance because they have the two extremes owns. Hence why you get the breast development due to eastern less body hecks. That's typically a sign of being female. It was the less muscle mass as well. Brilliant. So I'm just gonna go into our last section now, which is anti nature screening. Um, I've included this from the neck, just website for all students studying in the UK. It's really useful. I'm not gonna go through it now, but you've got it here for your reference. The main things that you need to know, as the Honda said, is a soon as a, um, female. Is that pregnant or even before that pregnant? And they know that once become pregnant, they start 400 mg of Frederick acid, which is the Honda said, reduces the risk of neuro tube defects like spinal bifida. Um then later on in the pregnancy, you get some blood tests for blood disorders. Such a six anemia of how senior, a blood typing blood grouping recess status on also fits over some infectious diseases as well. Such a syphilis, hep B and HIV Ondas. Well, diabetic eye screening is performed as early as possible for any mother's that also diabetic. Um, And then we go on later in the antenatal process to offering screening ultrasounds and blood tests, which I'm gonna go quickly through now. So the maybe they're two main old sounds sounds that, um, that we have in the UK, So these anti NATO scans, basically used to identify mothers with babies, are high risk of particular disorders. These are high risk mother's. These high risk groups, Mother's can be offered invasive diagnostic tests before their birth, and they're also offered more support after their baby is born, and I'll go into those invasive tests on my next flight. So the first ultrasound scan that mother may have is a 12 week dating scan. This is not sound form between eight and 14 weeks of gestation on. It basically checks for the estimated delivery date of the baby on, but it also checks The new mucus translucency, which is a separate for, is mainly for down syndrome. Then you have the 20 week fetal anomaly scan, as this is another ultrasound scan, which can be performed between 18 and 21 weeks on. This checks for the presence of other physical abnormalities such a congenital heart defects and things like that, particularly any defects that you might find associated with the three tries, um, is that we've talked about, um, each of these ultrasound scans then comes with the blood test on Go. The 12 week dating scan comes with the combined but test on the 20 week fetal. Normally scan comes with the quadruple blood test on By, Like to remember this as the blood test being enough, Better order it basically so. 12 weeks scan is earlier, so it's got the blood test, starting with the earlier letter of the alphabet and see where is the 20 week ultrasound is later. So it's got the it stopped has the blood test that starts with the later left off the alphabet, which is Q four quadruple. So, as I said, those ultrasound scans pick up our high risk mothers that may have fetuses that have congenital abnormalities on. At this point, they will be offered. They don't have to take it up, but they may be offered a ninja a sieve diagnostic test to find out whether their baby will have a birthday effects such as Down syndrome. As I said, it's not offered every pregnant woman. It's only if they are identified as having a higher risk of the condition just because these tests are invasive than they come with their own risks. So the two that you, you will need to know is amniocentesis on chorionic villus something so amniocentesis is used primarily in the diagnosis of our crimes. Oh, no abnormalities there. Was there any fetal infections as well, and it can also be used for sex determination. Eso. In this procedure, amniotic fluid is aspirated or basically drawn up or removed with a needle guided by ultrasound from the amniotic sac of the Arctic cavity. And what does it it takes in the amniotic fluid surrounding the fetus? On Within that fluid are fetal cells on. These fetal cells can then be tested on that can tell us whether a baby has a birth defect call. No, um, the important thing you need to know for this is that is performed later than CVS around 15 weeks, and it has a lower risk off miscarriage, about 1% in controls. Chorionic villus Something on CBS. It tests the Village of the percenter, which also contain the the baby's genetic makeup On. This can also check for genetic or birth defects such as downs or cystic fibrosis. Um, this villa something can. You should be done through the cervix, or it could also be done through the abdominal wall, and the thing you guys need to know is it is performed earlier about 11 weeks, but it has a higher risk of miscarriage over 1%. But these two invasive diagnostic tests are being formed less now because there's something upcoming and new, which is called Nips uh, which I'll talk to now, Uh, lip is they ski a non invasive diagnostic testing. Um, on this examines peripheral blood from the mother viral. A blood test from the mother. So you don't need to go anywhere near the fetus. It'll it is simply just above tests for the mother on how this works. Is that, um, cell free DNA. So basically DNA not found with them. Cell from both the mother on the fetus is found in the maternal D in a found in the maternal bloodstream. Sorry. So when the mother has above tests and that is extracted on genetic testing is performed. Small fragments of the fetal DNA are within that blood, and therefore they can be extracted and checked for genetic abnormalities. It has a lot of benefits, is the same. So it's highly after it nipped. Testing uses next generation genetic sequencing technology. And it has a detective right over 99.7. Um, I said it hasn't got asshole. I risk of miscarriage because you're not going anywhere near the fetus. It'll you're just taking a maternal blood sample. Um, it's also can be performed earlier as well as it could be done as early as 10 weeks adjust station on. But it has. It has a lot of benefits, and it contest. There are a lot Three of our tries, um, is that we mentioned. And however, just like the other invasive diagnostic test that I talked about in previous side, it's not offered to every woman just because, um, it's only offered to those are high risk. Um, and that's mainly salary the moment because the cost is so high. It's about 450 lbs to perform one of these, so it doesn't the sadly, the cost doesn't outweigh the benefit. Certainly. So if I've got time, I just like to do a couple of SPS, if that's okay. So what? Some of mine. They quickly launched the pole. So our first question I've only got two today. Which of the following is not a principal teratogen ESIs bring it, and I'm gonna in the pool there. Well done yet. Well done, everybody see? Yeah, I think the majority of you put day, and that is the correct answers and well done. So yeah, it's a previous exposure to other two Russians. And if you go back to most light on the three principles attracts Genesis on, you'll see that the others are the three principles with the timing and the leg being one together. And finally, this is one that you guys can do on your own time. What I've done here is I put some different features off some of the different trees. Oh, knees. And the mornings only is that we talked about today on. But if you go through on do you can just work out in your own time. Which of those features corresponds to which syndrome? That's really good. Way to check for your vision that you've understood today. Um, but these will be on the slide over it. Spoil it. But thank you so much for this thing. I hope that was really helpful. And I'll pass over to Toby. My name's TB. I was gonna That's a hard quickly set up the power port it slide. Thank you for for, um, for staying on staying on so long. And I'll try and keep my slides this concise. I can, um and hopefully that helpful to you. Okay, so today, today I'm going to be talking to you about pedigree diagrams. Um, so a comment in inherited patting imprinting. They're hardly buying bags question and then imprinting disorders. So I would start with, um, in this power point. I've, um, say then, Patrick, you diagrams affected males. Females while have left uneffective males and females unshaded with carriers either with a dot within the shape or harsh aided shapes. Now I wanted to mention consanguineous on couples. So where there's a line drawn between each couple, they're married. If there's two lines, then that both couples come from a related family now this is important in genetics because it increases the risk of recessive conditions being passed on. So this is because if I say a mother has a recessive condition with in her family on, she marries a man from the same family, then the likelihood is that that condition will also be in That person's may was family if they come from the same family. Okay, so, first of all, or, to say, more dominant conditions, um, these have a 50% chance of being passed on Teo offspring if one parent is affected by the consent by the condition on here, I made a list off common or so more dominant conditions on in particular, I wanted to make a night of their broccoli one and broke a team you take in Onda. This is significant because which explains why there's such a strong genetic link in the breast and ovarian cancers. Did it? Okay, moving onto orders. I'm recessive conditions on the risk of an autosomal recessive condition is a quarter times by the father's carrier risk times by the mothers carrier risks. This will make more sense in the next light. Um, that the just of it is, you need both the mother and the father to be a carrier for the condition for their offspring to be affected. And again, I've made a list of helpful conditions to know for exams. Um hey, what you can do kind of her in your in time. Okay? So had ever drawn a genetic cross, um, on in the public school in the public square. So it shows, um, how, If you have both parents is carriers, then there's a one in four chance of your hospital being effected, and that's represented by the double bees. Now, um, if you're asked, what's the risk that the healthy sibling off on effected person will be a carrier. You might think the answer to this is one after it's two out to out for, say, 50%. However, this isn't the case because the question asked, What is the risk that the healthy sibling would be a carrier? So this bruise out the healthy sibling being affected by the condition is that healthy? So the actual answer is two out of three so excellent recessive conditions. These conditions basically only effect males. Now, this is because mayors only have one extreme same say, um, if that X chromosome was affected, then they have no other extreme zone to compensate. So that definitely gonna be affected by the condition. Whereas females, if they have one affected cream same, then that only gonna be carriers for the condition. Now, this means the excelling, recessive conditions often skip generations like shown by the diagram, um, and again common conditions red green, color, blindness, hemophilia, fragile X and dream on Duchenne's muscular dystrophy. Okay, now the hardly wind down you crazy in, um is useful gration that she's to help calculate the incidents off conditions within a population. Not to use this, you have to presume that an alley. Oh, can only be either dominant or recessive. So if you add together all of the dominant AL yours plus or the recess, uh, values, that's all the allergy was together on this week. Well, one say people ski equals one. Now, if you square both sides of the equation, um, you end up with on this breath these brackets, which you can expand to make peace Grant plus TPG excuse Grad schools one where Peace Grad is thehyperfix, I guess Dominant T p Q is the carriers of a condition. And then cues grad is the homozygous recessive members of the population. And there's an SBA on this later. So, uh, make night. Okay. Now, actually, um, dominant lethal conditions. So before I talk about this, I just wanted to explain a little bit about bar bodies. So in females, you got one inherited X chromosome from your mother on one from your father. Now, 14 days after fertilizer fertilization, either the paternal X chromosome or the maternal extremism is turned off on inactivated. So this means after 14 days, um, female cells only contain one active X chromosome. Now it's random, which, um which creams own booby turned off of the paternal or the maternal X, and as a result on the service that go on to divide from these hours could be full of paternal cells. It could be full of maternal cells. Or you could get a mix of paternal on butter. No X crimes themselves. Um, now, in males, you don't get Barbara the formation. So if you get an X linked, dominant X chromosome in the mail, then the pregnancy will not be viable, since they're know healthy X chromosomes. However, in a female, um, if you get Nextlink dominant Lethal cream zone, then some yourselves will be affected. Where some yourselves this affected chromosome will be turned off. I will become the body now. As a result, pregnancies can actually be be a viable, um, if you have some healthy and some unhealthy active X cream zones. So, um, so you have some healthy cells and some affect your cells. So here I've got a condition could incontinent pigmented I, um, which is skin pattern. We have some healthy in some infected cells. That was just a nice example. Okay, Okay, Now, a nice way to move on is talk about Ms. S is, um, say emphasizes in, um only some cells in the body are affected by condition. If this is constitutional, then you get a mix of your body cells on do germ nurse hours being affected. So your reproductive Selves on offspring might be affected by the condition. In somatic meet Mrs um your German, um, cells and gave me It's it's bad. So you will not pass on your condition to offspring. Where's the opposite is true and germline mutation and you will pass on the condition chart Spring. Okay, imprinting. This is a little bit complicated, but I'll do my best to explain. So in your body you have a tan. You on maternity inherited crimes times, um, on on these crimes aims. Sometimes you get areas off the maternal crime. Same inactivated, leaving only the tendon there attended creams I activated and the same vice versa. Now this is fine normally and healthy. However, if you get a micro lesion in an active part of a maternal chromosome, where the tendon portion is inactive and you're left with my functioning chromosome on As a result, you can't code for any proteins at that point on the crime zone on, um, you can be affected by, um, imprinting conditions equally the same kid in the kind of fight vice versa. If you get mutations in potential crime scenes. I know. So I if you accidentally inherit to maternal creams, Ames is good. You need printed dies. Oh, me. And in this case, you will not have any active potential crime. Same. So to say, the same probable car. Yeah. Now imprinting, um, two main conditions I want to make Sun is angle minutes and drain on foreign German syndrome. I'm proud of really syndrome. Um, now this is GI to you and imprinting disorder on chromosome 15 of the long arm comes in 15 between points 13 and 11. Um, on D this, um So, in part of really syndrome, you get a defect where the potential there's a deletion in the pattern. Oh, um creams and say you don't get the, um the genes that was created for by the 10 of crimes, um, on an angle mints and drain your mother's chromosome. Have insulation in. So you don't get those those genes kind of four. Now, wait. Remember the presentation of these conditions is to think about as paternal genes promote growth. So I'm proud of really syndrome. You don't have your paternal jeans because their jeans being dilated. Um, so you end up with small babies on these small babies will seek to grow, so they will consume lots on their get disorder where they're hungry or the time on you end up with obesity. Uh, what's, um, then an albumin syndrome? You get the Children with a taxi, inappropriate laughter and learning difficulties. Okay, now, just a sp a to finish off with on. So using the hot hardly wind baby creation, women with cystic fibrosis is planning on having a child with her husband. He does not have the condition. Now, 65 braces has an incidence off one out of 2500. So what is the risk that the child will have cystic fibrosis? Now, you might need a bit pen and paper for this, so I'll give you a moment on. Don't worry to be doing today. Um, is quite tricky to work out, so it's important to know it's okay. I'm gonna start the pole now. Okay, So it looks like most people have said see on. Um, the people who said see would be correct is see on explain why, um so instance, assisted by braces is one out. 2500. So this is Keys grad in the honey white bag in, So Q is one out of 5. 50 Which means pay my siku 49 out of 50. Um, now, if you work out the dads carrier risk, um, then this is 0.3 92 on the does carry risk. Um, possible A cystic fibrosis is ah, half than it's that number times by half, which gives you about on. But if you want to. Okay. With this further, um, please fill out the feedback form on. You can receive the slides on. You can look over this in more detail. Okay. So yeah. Thank you. Thank you. Everyone for coming. Um, it's been really nice. Start off. As events said, we'll be doing this every Monday after each case. Thank you. Thank you, everyone. Fasting. Please fill in the feedback for the recording. If you feel in the feedback from the recording is available on metal. It's up. If you will be granted access immediately. Um, so how can you stop the life training