USMLE Step 1 Linkage Disequilibrium
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- Опубліковано 5 жов 2024
- Everything you need to know about linkage disequilibrium for the USMLE Step 1. You will learn about alleles, chromosome loci (plural for locus), and how gene proximity can make all the difference.
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Oh man, this is the best video out there. I have been reading the same 3 pages of the book for at least 2 hours and I couldn't understand a thing. I watch your 7 min video and now it's all clear. Thank you so much!
I’ve struggled to understand this for long and you cleared it up so tactfully. Thankyou so much.
My first time commenting on an academic video. I simply say thank you!!!
finally someone explains and I could understand linkage disequilibrium thank you!!
You man are a genius, never understood it in the lecture, but now I do, thx!
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This was an amazing simple explanation. Are there any videos in which we could have a clear view on how LD is important in GWAS and provide a clear understanding on how to interpret the haplotype blocks? Many thanks!
That was an amazingly clear explanation for a topic I got stuck at understanding from papers! Thank you!
I am very grateful for your explanation. I spent all day trying to understand this and it was made very easy with your video.
Really thank you very much!
Highly appreciate the attempt. I think I have a legit question.
1)If the alleles are far apart, they behave as if they are on diff chromosomes, and recombine the maximum, giving rise to 0.25:0.25:0.25:0.25 frequencies for the 4 combinations (AB,Ab,Ba,ab).
2) if they are very proximate to each other they are almost 100% linked which gives us increased rate of AB, ab, max of 0.5.
3) If their distance is neither far nor too close, then recombination can happen few times and ratios of AB, ab will be less than 0.5 but more than 0.25.
case 1 is linkage equilibrium . case 2 and 3 are disequilibriums (in both cases the frequency is more than the case 1. what is the scenario that the frequency could be less than 0.25?
Now the linkage disequilibrium definition says, it could more or less often than expected by chance alone (randomness). how can it be less often 0.25?
by the time I typed the above, I realised it could be new mutation incidence.. am I right? or missing something?
I just tried to think about something that could make cause the frequencies to be less than 0.25. The only thing that comes up to my mind is chromatin structure. If two genes are divided by a region rich in euchromatin than I think it is more likely for crossing-over to occur in that region. This could possibly make conservation (i.e co-occurence) of the two genes less likely than 0.25. Is it clear? What do you think about it?
Maybe selfish elements that suppress one allele over the other? Or rapid population expansion that introduce new variants into the population?
i rewatched this part of my lecture 5 times and still didn't get it, with this video i understood within 3 minutes. thank you!
sublime explanation, was really struggling with this when it came up in the extended phenotype
Awesome video! So intuitive and helpful. Thank you!
So Linkage Analysis involves the analysis of basically linkage of Chromosomes during division.
Now first each set of Chr should be heterozygous for each trait at a foci.
Under Linkage analysis you can observe Linkage equilibrium which means the Alleles on the SAME Chromosome would still have characteristics of Independent Assortment as long as they are far away.
Linkage disequilibrium means when the frequency of a combination occuring is higher than that which we would get by chance.
That's what i learnt
The explanation given in this video is great. Thank you very much.
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Thanks a ton!!! I was looking for this clarification for a long time. Finally, I found it! Thank you for making the video.
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amazing man (y)
i was so confused with this thing. Cheers :)
It is now crystal clear,thank you
Thanks! I finally get it!
Great video, I finally understood the whole thing! Thank you so much!
I was wondering - you keep saying that this or that occurs whenever "two allels" are close or far apart on a chromosome. Wouldn´t it be more correct to say that "two genes" are close or far apart?
Hey! You are right that they could also be referred to as genes. That said, they can also be referred to as alleles too, because the diagram is showing 2 genes and 4 alleles. To keep it simple, we were referring to each letter as an allele. The letter "A" and "a" are the same gene, but different alleles, while "A" and "B" are different genes, however, "A" and "B" are also considered different alleles for a different gene. Hopefully that provides some clarity!
thank you so much, very informative and helpful♥
It makes total sense now! Thank you!
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Thank you. And Wouldn't it be also called linkage equilibrium if two alleles are on the separate chromosome? UW has given example of equilibrium as on seprate chromosome.
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Great explanation, thanks.
Brilliant Explanation Mate !!!
In minute 1:41 he says that A represents a gene, and B represents another gene, but then when talking about linkage equilibrium A and B are referred to as aleles. I'm not sure I'm understanding correctly the difference between the two.
amazing explanation
At (1:42 seconds) you say that A's represent a gene (with big A being one allele and little a being another allele of that gene) and B's represent another gene (again with its corresponding alleles). But then later in the video you use A and B to represents alleles (3:40 seconds). Not sure if i'm the only one that saw this or if I am missing something but it confused me a bit.
So from my understanding when talking about linkage we are talking about two genes and how they are inherited. With linkage disequilibirum we have the alleles for two different genes in close enough proximity that they are essentially inherited together the vast majority of the time and do not follow the typical independent assortment (where the inheritance of two genes are independent of each other). Is this correct? Thanks in advance!
I do agree with you. This question comes to my mind also. Actually those two alleles are the allele of two different genes.
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Hi, I'm still confused and I wonder if you can help.
The example at 2:44 says that allele A occurs 50% of the time and the other 50% of the time, allele B occurs, "what is the chance of having A AND B".
If we pretend A is brown hair and B is brown eyes, what the example is saying is (at least the way I understand it) half the people have brown eyes and half the people have brown hair.
This statement is a problem since having a certain hair color doesn't automatically decide the eye color. Saying half the people have brown hair (A) doesn't tell you their eye color, and saying half the people have brown eyes also don't tell you their hair color. No matter what hair color they have, they must also have an eye color and vice versa. Therefore the question about AB makes no sense to me.
Should it not therefore be "Big A dominant brown hair occurs 50% of the time and little a recessive blond hair occurs 50% of the time, what is the expected frequency of getting Aa?" (and since A is dominant while a is recessive, the phenotype would be brown hair)?
Also linkage [dis]equilibrium is counterintuitive to me: if 'linkage' means "on the same chromosome" and 'equilibrium' means "constant or same": then if 2 alleles are close together like at 6:09, then they are more likely to be inherited together since there are less chances of them being separated while undergoing recombination. Since they are more likely to be"constantly" inherited together, I'd assume this means they are at linkage equilibrium.
Based on allele frequency, whether, We can calculate haplotype frequency??
So, the linkage disequilibrium is the reason for distorted segregation ????
Perfect and succinct! Thank you :)
Thank you sooooooooooo muuch.
Thank you. This is very helpful :))
You are awesome!
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quick question: do the chromosomes "break" twice (I mean on two places) when linkage disquilibrium occurs? The two pictures showing Ab and aB für LD suggests this, or could it also be that there is a small "blue A part" and a much bigger "pink b part"? thx
Thanku so much❤️💖
I don't understand why there are 4 chromatids in the beginning and 2 chromatids when you explain linkage equilibrium?
If I'm right, I think he's trying to say the alleles are more likely to be in linkage disequilibrium when they're on the same chromosome, whereas if they're on different chromosomes, they're going to be in linkage equilibrium. However, I do believe that LD can occur even if alleles are on different chromosomes.
omg im gonna cry i finally understand it
Just amazing
Brilliant!!! Thankyou so much
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I'd ve loved if you spoke just a liiiil bit slower haha (non native eng speaker ^) ,, still helped me a ton tyvm
Thankyou
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excellent
What is the reference used for this video? Thanks!
Hey! We referenced a whole bunch of different sources to bring this all together so that it would be as cohesive and seamless as possible. We hope you like it!
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AH okay so: Linkage: 2 alleles on same chromosome regardless of the power of that bond....... when that link is weak and they can be swapped with another chromosome through crossover, that is link eq. ----- when that bone is strong because they are close and they are likely to stay together that is link DISeq. Finally! cool. ty.
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When you state that “linkage equilibrium refers to alleles that are found on the same chromosome” don’t you actually mean genes?
Hey! You are right that they could also be referred to as genes. That said, they can also be referred to as alleles too, because the diagram is showing 2 genes and 4 alleles. To keep it simple, we were referring to each letter as an allele. The letter "A" and "a" are the same gene, but different alleles, while "A" and "B" are different genes, however, "A" and "B" are also considered different alleles for a different gene. Hopefully that provides some clarity!
@@physeo-USMLE good explanation. So what are we referring to here when we call allelic frequency, essentially of 2 diff genes? where as when in the context of Hardy Weinberg law it is of same gene?
Thank you so much for this. I hate genetics lol
Linkage Disequilibrium is Linkage KISSequilibrium- the alleles are toooooooo close! ya Feel me saaaaaawn?! Mnemonics for life. Live the Dream. (Terms and Conditions apply, dreams aren't for everyone, mnemonics may cause tooth decay, and headaches, Tom Cruise tried to eat his baby's placenta, hashtage kisseekisseedisseedissee)
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To be more accurate, 1:54 shouldn't you have said "because each of the GENES are on different chromosomes", instead of "...because each of the ALLELES are on different chromosomes"?
linkage disequilibrium starts at 5:15 !
The Intro is Important
Am glad he talked about Linkage equilibrium
i love this. so clear
i have a question, that percentages were based on population right? for example in linkage disequillibrium, 49% of population tested, will have AB spermatid, and then just 1% of population will have aB... am i right?
You've made a frustrating question much more understandable - thank you.
Thanks! I finally get it!
thankyou