# HMB265H1 Lecture Notes - Lecture 22: Heritability, Reca, Hypercholesterolemia

Thursday, March 26, 2009

- “Mendel Gets Normal”, an introduction to quantitative genetics. Today

we’re going to talk about how Mendel gets normal and by normal he isn’t

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, let’s take a step back, taking stock of

where we’ve 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 we’ve 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 couldn’t be all that simple. For example, the law of

independent segregation, that is, the way in which 2 traits segregated

within an individual couldn’t 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 Morgan’s 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

we’re 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 don’t. 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 we’re finally going to get at trying to understand how we observe

more quantitative variation, not qualitative but quantitative variation in

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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 doesn’t 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 we’ll look at today. Today we’re going to consider very

simply, an intro to quantitative variation & quantitative genetics which we

will continue in the next 2 lectures so we’ll 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 showing changes in body size, height and shape, body

weight, body mass index and so on.

- We know that we can see continuous 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 we’re

just looking at body size. We know the factors we see around the outside

together with genetics will determine the trait.

- Things that are really coming to light as of recently are things 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 question again, can simple Mendelian genetics explain 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 we’ve

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.

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- 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 you’ve 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 we’re 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 highlight right now is if we take a look at this

distribution, we would know that the individuals without the trait would

be homozygous recessive but if we were to take a look at individuals that

had the trait or the trait is present without genotyping them of course, we

would have no idea whether they were homozygous dominant or

heterozygotes, we would only know that they had at least 1 dominant

allele. So in fact by looking at just traits of individuals for this class we’re

blind to what is going on at the genotypic level. Just by looking at the tall

people, we don’t know if they’re heterozygotes or homozygotes. That is

what is important!

- So that is what we’ve seen already so far. The point he wants to raise is

things aren’t that simple. Clearly they’re not that simple.

- We have an example where things aren’t so simple or as he likes to call

it, a wrinkle on Mendel’s laws. Going back to Lecture 17, we know that

dominance is not always complete just as he showed us. In fact what we

see every now and then is that one can have incomplete dominance.

- Recall incomplete dominance are those instances where one individual

here with 1 allele shows 1 extreme of the trait, the other individuals with

the other allele show the other extreme of the trait. So white to dark blue

in this instance whereas heterozygotes show an intermediate of the trait.

- And he provided examples of this in that lecture, one he said he’d touch

on again.

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## Document Summary

Mendel gets normal , an introduction to quantitative genetics. Today we"re going to talk about how mendel gets normal and by normal he isn"t 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, let"s take a step back, taking stock of where we"ve 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 we"ve 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 couldn"t be all that simple.