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PETER REDDIEN: Now you and I, all individuals in this room
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will vary roughly about one nucleotide for every 1,000
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nucleotides.
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So humans are very, very similar to one another
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at the DNA sequence level.
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One in every 1,000 nucleotides, on average, are different.
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But nonetheless, we have a 3.2 billion nucleotide genome.
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and there could be heterozygosity and so on.
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So there's roughly 4 to 5 million sequence differences
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between to any two individuals.
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So that's a lot.
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So if you do the sequencing, you've
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got 4 to 5 million differences to sort through.
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So it's literally a needle in a haystack to try to find this.
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So how in the world do we do it?
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There's plenty of human disease genes that have been found.
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You could take model organisms, like our paralyzed fly,
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and you can find the gene and study it,
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try to do things with it.
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So how do we do it?
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Sequence lots of individuals.
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Well, so all the individuals are going
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to have a lot of variants, and if there's some clonal origin,
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let's say, of the variant like one paralyzed fly, or one
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mutated individual, then all of those variants
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will be present in all the descendants,
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depending upon the nature of crosses that have happened.
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But you could start working with that,
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the nature of crosses that have happened, to think about this.
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But if you sequence a lot of clonal individuals,
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you just find the same polymorphisms over and over
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again.
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But there is something to what you're getting at.
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Any other suggestions?
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So the suggestion is look at how far apart things are.
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But what things are you looking at
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to see how far apart they are?
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You're kind of on the right track.
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OK, so look at other things that are
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different in that individual that
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might be going with that trait?
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STUDENT: Yeah.
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PETER REDDIEN: OK.
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So that's good, and in general, that's
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the approach taken in a lot of human genetics, which
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we'll get into.
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Did you have a--
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So the suggestion was, if the location of another gene,
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can you use that?
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OK, that's great.
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So what you could do, so you remember the genetic mapping
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with yellow and vermillion and stuff, miniature wings on the X
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chromosome.
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Let's say you find, oh, I'm one centimorgan away
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from one of these, and the other one
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has been discovered from other work.
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Well, then I might roughly know the area
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of the genome this is in, because you've
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placed some genetic marker onto a physical map,
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a reference sequence.
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And I'm in between these known--
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from the genetic crosses, these known genetic markers.
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And I know their position on the physical map,
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so I know I must be in this region of the physical map.
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So that's good.
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That can start narrowing it down.
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Great.
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So I think we're getting on the right track.
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Let's now dive in to trying to do this in as efficient a way
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as we can think of.
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