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Lecture 22

Lecture 22- Quantitative Genetics

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Human Biology
Christian Campbell

Thursday, March 26, 2009 - Mendel Gets Normal, an introduction to quantitative genetics. Today were going to talk about how Mendel gets normal and by normal he isnt talking about going weird to normal but a normal distribution. So what this lecture serves then is an introduction to quantitative genetics. - Before we get started on that, lets take a step back, taking stock of where weve been so far with regards to our understanding of genetics. He will lead us from the beginning and considering where we just finished up in Lecture # 21 so going right to the beginning then weve seen this in each lecture right now. Mendel explained patterns of inheritance on the basis of what he saw happen with discrete traits, how they were passed on from a parental generation to a F1 generation eventually to a F2 generation according to discrete ratios. We saw that the way Mendel considered his traits couldnt be all that simple. For example, the law of independent segregation, that is, the way in which 2 traits segregated within an individual couldnt be as simple as Mendel described because of course, genes are linked up on chromosomes and we saw with Thomas Hunt Morgan in his lab took advantage of that fact to begin to assemble effectively the roadmap or maps to understand how genes were linked together on chromosomes. Where we finished on last lecture was what one of Thomas Hunt Morgans students, Alfred S, did to understand that linkage relationship from one gene to the next. - Just going back to last lecture, recall he started off by doing these 2 point test crosses, that is, looking at pairwise combinations of genes, hybrid individuals & he took this one step further to look at these trihybrid crosses 3 point test crosses to establish linkage relationships b/w 3 or more genes simultaneously. Doing this of course in Drosophila melanogaster & he did that simply by making crosses b/w females that were trihybrid individuals F1 individuals & crossing them with tester males b/c recall recombination only takes place to an appreciable extent in females & simply by counting the offspring & their phenotypes, looking at then the parental types, the single recombinants & the double recombinant individuals. On the basis of that info & how we use that to calculate recombination frequencies, he was able to establish genetic maps like the one we constructed in the last lecture. We walked through that in the last lecture & the steps we went through are precisely what we must go through as we construct genetic linkage maps for both your tutorial and for the exam. - That is where we finished off & what he talked about was how we could use the same method iteratively (over & over) to construct maps of the way in which traits were linked together on chromosomes & more specifically we should say linkage groups for any given organisms & he finished with the tomato. - There is an important point here with regards to the tomato & that is were still talking about segregation of discrete traits just like what Mendel was looking at, that is, traits that show some kind of qualitative mode of inheritance, either you have the trait or you dont. That is how these maps were assembled but of course we know in the real world that is not the way in which variation looks, particularly as we look around the room. We know that the world looks more like the pictures he shows at the beginning of every lecture. - Now were finally going to get at trying to understand how we observe more quantitative variation, not qualitative but quantitative variation in traits, that is where the variation in traits is more continuous, that it is more difficult to see distinctions b/w discrete forms of the trait and that is what he wants to consider today. - Today he wants to address the following. Phenotypic variation as we just saw doesnt always appear discrete, that is qualitative, but rather continuous or quantitative. Can genetics explain this kind of variation and if it can, what are the tools that we use to describe it and how can we look at the patterns of inheritance for such traits? - This is what well lookat today. Today were going to consider very simply, an intro to quantitative variation & quantitative genetics which we will continue in the next 2 lectures so well take a look at continuous variation, additive inheritance & the most important equation in genetics, P=G+E. - Here is the question he said he would address or at least begin to address in this particular lecture. Can genetics explain quantitative variation? - We know that many traits appear quantitative in nature, he just showed us examples of tomatoes but of course, we know that this is also true for humans. - Here he is sh owin g chan ges in bo d ysiz e, heig ht an d shape, bo d y weight, body mass index and so on. - We know that we can see continuo us variation in such traits and we know that such traits frequently show a so-called normal distribution, that is a distribution that shows a stereotypical bell-shaped distribution about a mean where the mean of the population is where the frequency of the individuals is highest, and out at the tails of the distribution obviously the frequency of those individuals is the lowest. - The question is, can Mendelian genetics explain this, and can such traits have a genetic basis? - We know that there is a certain problem we must consider. When we see these traits, we know they cannot just be a product of genetics alone. We know there must be influence of environment on such traits so here were just looking at body size. We know the factors we see around the outside together with genetics will determine the trait. - Thin gs that are re al ly comin g to lig ht as of re nt ly are thin gs like bacteria, microbes we have in our gut will determine if we will have a svelte physique or less svelte. Food abundance, amount of exercise, type of food eaten, whether we were exposed to specific pathogens, we know all these factors will act upon genetic material and work together to give rise to that phenotype. - So quest io n again, can simple Men del ian genet ics ex plain this? Can such traits have a genetic basis? Can we actually track traits where we know that there is contribution of environment to the trait? Can we actually figure out where the genetic basis of that trait is? That is what he wants to address today. - The way he wants to get at it, to see if we can actually dissect such complex traits is by taking a step back & looking at what weve understood right from the beginning of these series of lectures & that is taking a look back at first principles & what we know so far about the inheritance of traits. What we started at the beginning of his lectures is this: simple Punnett square looking at a simple segregation and reuniting of course of alleles at one locus. - So youve seen this before. We know that with simple dominance mode of inheritance that if we cross monohybrid individuals, that is, 2 heterozygotes together with each other, what were going to see is the stereotypical 1:2:1 stereotypic genotype ratio and the 3:1 phenotypic ratio, that is, what we see presence or absence of the trait. - If we were to take a look at that as a frequency distribution graph, here is what we would see. If we took a look at the trait measure, what we would find is that in the absence or presence of the trait and the frequency, we would have one individual who does not have the trait for every 3 individuals that have the trait so there we go. - Of course what is underpinning that distribution and that is an important point, what is underpinning that distribution is on the left hand side, the genotype of the homozygous recessive individual and on the other column, the individuals that have the 3 within this distribution, we have a mixture of homozygous dominant and heterozygotes. That is going to be very important for something we will take a look at next lecture so put a star beside it and say see Lecture 23. - What he wants to hig hl ig ht rig ht now is if we take a lo o kat this distribution, we woul
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