Cambridge Interview: Strong Biology Applicant

So can you tell me a little bit about your interests? Yeah. I’ve been doing A Level Biology and Chemistry and in particular I’ve been interested in genetics, having studying Biology and I would like to explore that a bit further as well in university and beyond. Is there anything else you’ve been doing for your own interest in July? Yeah, I did a project recently in my summer holidays, working in a lab in Oxford where we looked at bracket one and bracket two genes in breast cancer and we looked at imaging certain pathways, hoping to get a paper out, I’m writing that at the moment. That sounds really interesting. That’s really great. Yeah, and we found we looked at a certain pathway that’s used to repair defective or damaged DNA and we found that there’s worth in sort of cultivating models and see if that works over here as well. Great. And I think you’ll be lucky with what we’ll do in the interview today. I thought we could do some genetics questions. Okay. So let me start, could you draw a Mendell square for a recessive disorder? Can you name a recessive disorder? Okay. So a recessive disorder that comes to mind would be something like sickle cell disease. So a Mendell square would maybe look something like this where we have mother’s side over here and the father’s genes over here and if I draw a capital A and a little a denoting one of the different leals of the same gene. And again for the father. I assume they’re both carriers ie they both have one each, you could have, I would suppose, four types of inheritance. You could have two large A’s or two of one type of leal, two of another type of leal and then one of each. So if the little ‘a’ denotes the sickle cell trait there’d be a one in four chance of a small a that the offspring would inherit or express sickle cell disease. Right, that’s great. And if you had a dominant condition, how would this change? Is it okay if I turn the page? I think you can use this again? Okay, sure. If you had a dominant condition… Could you name a dominant condition? Yes, so certain types of polydectomy are dominant conditions, Huntingdons disease. So if you had a dominant condition, assuming that one parent would obviously have the condition themselves. So if we change it and say… Let’s say the father has two big A’s there would be a 50 per cent chance that the offspring would get the disease as well because there’s a 50 per cent chance that they inherit one of the defective genes. Great. So I want to talk to you about a different condition. Okay. Colour blindness. Okay. Can you tell me anything about colour blindness? I don’t know a lot about colour blindness, but from what I have heard it’s something that’s more common in men than it is females and there are kind of different wavelengths of colour blindness that you can get. You can be blind to certain levels of light, so red, green… That’s exactly right. I want to go on more specifically. The first thing I found very interesting about this difference in female and male colour blindness. Do you know why that is? I haven’t been told why, but I would guess that it would have to do with generic inheritance of it. For example, if it was inherited in a manner which was X linked and therefore which only the male would require one defective copy, as they only have one X chromosome, then they’d be more likely to get it whereas the female would have two X chromosomes and therefore carry…another X chromosome which could compensate. Right, exactly. So colour blindness is, as you said, inherited on the X chromosome, but what we actually see in the real world is that there’s a significantly smaller frequency of colour blindness in females than would be expected from the male inheritance. Okay. Can I just ask you to clarify that? So there’s the smaller in females… There’s fewer females who are colour blind than you would expect from the frequency in males. So can you propose some reasons why this might be from your knowledge of colour blindness? So there’s less females that are colour blind than would be expected from males… From what you’ve just explained about the X chromosome. Okay. Yes. I imagine that if they had one defective X chromosome the other one could compensate. I’m aware that in most conditions, in most chromosomes that because there’s two inherited, one is kind of dampened down, I believe, and therefore perhaps if the X chromosome… the defective X chromosome is inherited for colour blindness, that is the one that’s the X chromosome that’s shut off in the two Then that trend would not be manifest. I suppose that would be it. So if we return to the Mandell square. Sure. So if I told you five per cent of males are colour blind. How many females would you expect to be colour blind if we assume that all colour blindness is on the X chromosome? If five per cent of males are colour blind, then… Is it okay if I just think about this for a moment? Yes, that’s alright. Take all the time you need. If five per cent of males are colour blind then they would definitely pass the X chromosome on to their daughters as daughters have to have the two X chromosomes. So the daughter would have to be a carrier at least and have at least one X chromosome. If their mother did not have colour blindness or even a chromosome denoting it, wasn’t even a carrier, then there is no chance that the female could be… I suppose it’s probably easier if I try and draw it out. So if you have a male which is… That’s a big C and a small c. The small c being sort of colour blindness. So if that’s a male he’s going to pass the X chromosome on to his daughter and if the mother is a carrier, so she has big X and small x, small x being the colour blindness gene, then there is a 50 per cent chance because it all depends on which X chromosome the daughter gets. If the mother didn’t have colour blindness and she wasn’t even a carrier then there’s no chance that the daughter would show colour blindness because she would not inherit two correct X chromosomes. She would only inherit one and that’s from her father, and she could only therefore be a carrier at best. And again if the mother had no signs of colour blindness, wasn’t a carrier, then there’s no chance that the daughter could be a carrier, is probably the best I can explain it. Right. So if we think about the actual numbers. So you were talking about before that the men can only have one X chromosome and so all their colour blindness is all that X chromosome. So five per cent of males are colour blind. That means that there’s an allia frequency of five per cent. So five per cent of X chromosomes are faulty. So we know that women have two X chromosomes, so given that X chromosomes are five per cent faulty, what would the incidence be expected to be from that? Well, if the mother was a carrier, if there’s 1 in 20 over here, 1 in 20 over here would be a 1 in 400. But then you have to think of… it depends what the mother is. I mean, if the mother’s a carrier then there’s 1 in 800 because there’s a chance that the daughter might not… So very small number we’re talking? Yes. Very small numbers here, but they’re actually even smaller and to understand that we’ll look at the protein mechanisms. Okay. So do you know anything about how colour vision works, the protein mechanisms of it? I don’t. No Have you ever heard of Oxcin, the protein? I’ve heard about it, yes, but… So you know you have three cones, three types of cones for three different colours, red, green and blue. So when you have genes, how do they work? How do they manifest? They would manifest themselves in proteins, so I mean they’ve had…their translation to produce proteins in the… Exactly. So you have a gene that makes the protein, and so Oxcin is a protein that’s sensitive to light. So when you have these three different cones, how might the different frequencies of light be caught by these colours? Do you have any suggestion? They could have different types of protein which are encoded which could be, I suppose, optimally excited at different frequencies of light which could differentiate between the two. Exactly. So we talked about three different types. Short, medium and long wavelength. So these short wavelengths prefer red, green and blue. Okay. So these different ones get different amounts of light. So when you have these different proteins, what kind of faults do you think happen in this frequency perception? I suppose if you had faults in the genes which led to different protein…different amino acids being encoded in the protein, they might have different sensitivities of light and therefore this might be shifted in either direction. Exactly. So the difference between these M and L, these can be shifted because they’re actually adjacent on the X chromosome. So when these shift, can you imagine how that might differ between a man and a woman with two X chromosomes when you get these shifts? Sorry, so how would the same mutation in a man and a woman cause different effects in their…? Well, for a woman obviously she has the extra X chromosome and if that hasn’t been dampened down then I presume that might be able to compensate to a certain extent. And what if both are faulty? If both are faulty in the woman and obviously not result in the man that could manifest itself as… I suppose if they shifted to different extents along here…So, for example, in one, the medium and long wavelength could be right on top of each other. So they’re essentially the same kind of curve and therefore there’s only two… There’s only sensitivity to two different wavelengths at the moment, two different types of Oxcins. Or we could have the situation which there’s only a slight shift and so there might be more of an overlap and there might be no overlap between one and more overlap with another wavelength of light which again might manifest itself in different… Right. So let’s say you’re a man, this one was shifted over. So this one and ML on top. In a woman you have a second chance in that there’s many ways these shifts can occur, as you say. So when you have the second X chromosome, even if it’s faulty the odds are it’s not faulty for the exact same shift between. So can you propose what might happen? What would make her less colour blind? Okay. So as you were saying, with the male you’ve only got one chance as such with the female. If you had a shift, for example like the one drawn here on one of the X chromosomes, and on the other X chromosomes you have a shift in the other direction, for example something like this… Between the two chromosomes you’ve got overlap in each of the wavelengths of light, so you kind of compensate for each other. Exactly. So this is exactly what happens and this is why you see this lessening of the frequency of colour blindness in females. So it was really good to speak to you. Okay. Do you have any questions now? Not now but maybe later. Alright. Well, thank you. It’s been very nice speaking with you. How did you think that went? Yeah, I thought that it got better as it went through the interview. At the beginning it was quite hard to focus on what exactly I was supposed to be thinking about but then as you gave prompts and clues as we went through, it’s easy to kind of [?] on what we need to talk about and think about, so it got better as it went along. As you say once you know the topic that you’re supposed to be talking about, think back to A Level and try to apply those concepts. I wasn’t sure what the right answer was but I felt that as long as I had a good go…a good attempt at what I thought was the right answer, you were willing to work with me and we got there in the end. Yes. I thought you were really good. I thought it was a really brave thing that you committed to this answer and you didn’t give up even though it was challenging and that you really tried and you used the materials that I gave here. The sketch was good and you used the diagrams appropriately. I felt that you spoke very clearly and you had good eye contact and focus and willing to listen and engage with what I was saying to you.