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MICHAEL HEMANN: Today, we're going
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to continue our discussion on mapping genes in the genome.
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We talked about mapping phenotypes relative to one
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another, which we can do, and we can
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identify a genetic distance, which correlates roughly
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with the physical distance between two different genes.
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But we noticed that this relationship breaks down
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at a long distance, and that really the longest
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distance that we can measure between two genes
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is about 50 centimorgans.
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It's actually less than 50 centimorgans,
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because we're getting multiple recombination
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events between these two genes.
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And so we are frequently underestimating distances.
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And we're not able to do fine mapping the way
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that we need to, because the whole purpose of doing
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this is we actually want to find a gene that we're
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looking for that has some alteration that we care about.
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So today we're going to talk about how we do fine mapping
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and how we use DNA markers to actually do
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that mapping in place of clear phenotypes.
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And so again, an example of the problem that we have
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is that we have intervals in the genome.
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So we have an interval here that's about nine centimorgans.
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And so that's roughly about three megabases in Drosophila.
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So that's three million bases, and so that
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would be about 30 genes.
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So we're looking for an alteration,
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and we have a choice of 30 different genes.
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And that's really too many, again,
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when we want to have a good sense of where to look.
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And this is an even bigger problem
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when we talk about people, because we
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can't do crosses between people, and we
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can't look at phenotypes and the segregation
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of different phenotypes in clear ways.
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There are some ways that we'll talk about later
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on in the class where we can look
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at some fine mapping in phenotypes,
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but we need a strategy to do fine resolution mapping when
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we do crosses that allows us to identify
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very specific regions of the genome
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where we want to have a deep dive
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to look for the alterations, and then
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do functional studies to try to identify
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whether the alterations that we find account for the phenotypes
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that we see.
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So the real challenge is how do we do fine mapping?
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So high resolution mapping in the genome.
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And the approach that we take is to use DNA markers.
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So what are DNA markers?
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Well, DNA markers are essentially just signposts
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in the genome.
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They're basically mile markers.
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They may actually have no functional relevance at all.
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They just define specific places in the genome
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that we can map next to.
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So you can really think of DNA markers
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as places in the genome.
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