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MICHAEL HEMANN: Today, we're going
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to talk about chromosomes.
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We're going to talk about mitosis and meiosis.
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And it's really an attempt to start
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placing genes in particular places in the genome.
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So in the past number of lectures,
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we've been talking about the gene,
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essentially, as a unit of function and phenotype,
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looking at pedigrees and crosses,
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and learning what we could learn without really
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having any concept of what a gene is or where it is.
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Now we're going to start placing genes within the genome.
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And so why do we do that?
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We do that because we actually want to be able to map the gene
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and identify the alteration.
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We want, in the end, to be able to sequence the gene
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to understand, what is the etiology of the phenotype
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that we're looking at?
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That tells us about the molecular mechanisms
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by which it's doing what it's doing
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and also potential therapeutic options
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for what we can do about it if we don't like the phenotype
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that we're seeing.
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So it really starts with the ability
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to map a particular phenotype to a particular place
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in the genome.
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And so let's start by thinking about the kinds of crosses
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that we've been working on recently.
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So let's just say that we have a cross that's
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between true-breeding wild-type organisms of some type
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and a true-breeding homozygous recessive.
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So let's say there are two different traits, so
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two distinct phenotypes, that are both
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caused by being recessive homozygous
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for a particular allele.
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So the little a, little a, little b, little b
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have a different phenotype.
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So we can cross these organisms together, and we get an F1.
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And the F1's are all heterozygous at this locus.
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And we can cross these heterozygotes together
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and get an F2 generation.
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And this F2 generation, as we've talked about before,
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has this phenotypic ratio of 9 to 3 to 3 to 1,
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where nine would be wild type, three
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would show one of the mutant phenotypes.
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If these are independent traits, three
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would show the other trait.
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And one of them, one out of 16, would
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show both of these traits.
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And so one of the key ways of examining this F1 generation,
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these heterozygotes, and the gametes
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that they're actually generating to go into the F2 generation
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is to perform a test cross.
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And so a test cross is generally a cross
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to a homozygous recessive.
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So if we take these F1 heterozygotes
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and we cross them with homozygous recessives,
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we can actually identify in this cross all of the gametes
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that this F1 is generating.
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And this is going to be really key in understanding
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whether there's truly independent assortment of genes
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or whether these genes are in close approximation with one
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another on the same chromosome, whether they're linked.
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So this F1 heterozygote--
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double heterozygote-- can generate four different kinds
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of gametes.
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It can generate big A, big B. They can
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generate little a, little b.
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They can generate big A, little b.
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Or they can generate little a, big B.
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So these are the four kinds of gametes that this F1
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heterozygote is generating.
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And we can designate these, basically, in two groups.
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One of them is parental.
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And parental simply means that these were the alleles
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that they inherited from one of these first-generation parents.
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So they could have gotten--
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the only alleles you can generate from this parent
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is big A, big B. The only alleles
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you can generate from this parent are little a, little b.
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So these we call parental.
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And the other two-- big A, little b and little a,
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big B-- we're going to call recombinant.
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Because it's some mixture of these first-generation alleles.
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It means that they got a big A from one of the parents,
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or they're passing on one big A from one
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of the parents and a small b from the other parent.
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So somehow, these are recombining
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in their germ cells.
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And they'll produce, when we cross them
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with the homozygous recessive in the test cross,
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they'll produce four kinds of progeny.
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One is big A, little a, big B, little b.
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It's just if you actually cross this with little a, little b.
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Another will be little a, little a, little b, little b.
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The other will be big A, little a, little b, little b.
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And the final will be little a, little a, big B, little b.
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The cool thing with a test cross is you can actually
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see all of these things.
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They all look different.
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So little a, little a, little b, little b is homozygous
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recessive.
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They have two traits.
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Big A, little b, big B, little b, they're totally wild type.
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And in a test cross, we'd expect,
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if they are independently segregating genes,
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that we're going to have a ratio here of 1 to 1 to 1 to 1,
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so equal representation for all of these.
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And this is really the hallmark of the segregation
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of genes that are on distinct chromosomes.
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It suggests that the genes, in fact, are not linked together.
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They're not close together.
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But they're actually on distinct chromosomes.
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So again, today, we're going to talk
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about chromosome segregation and what that looks like
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and what it means and perhaps what
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happens when it goes wrong.
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