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MICHAEL HEMANN: OK, so this idea of having a heterozygous parent
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with the condition is something that we can't always--
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we don't always have in humans because we can't control
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the inheritance pattern.
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We can't require one parent to have
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a particular genetic composition.
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But in flies we can do this, and in other organisms
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we can essentially create that heterozygote
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with the phenotype.
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And so say we have a phenotype.
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In this case, the phenotype is wg minus, which is wingless.
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No wings, an easy phenotype to see in a fly.
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And so let's cross a female that is a true breeding
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homozygote that is wingless so it has this phenotype
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and is homozygous for this allele,
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and is homozygous for the A version of the marker.
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And we'll cross with a male that is wingless plus
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and has the B version of that marker.
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So both true breeding homozygotes.
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And we create from this an F1, and the F1 is female,
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is heterozygous for both things.
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So it has one allele of this recessive wingless gene
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and is heterozygous for the markers.
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So we've essentially created this female
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through crossing that's going to be informative
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as she passes these alleles on to the next generation.
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The meiosis that she has are going
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to be able to tell us whether this mutant allele or this wing
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allele is segregating or not segregating
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with a particular allele of this marker with A or B.
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So we can do a test across here with a male
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that is homozygous recessive for wingless and has the A allele.
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And we can look at the gamete genotypes.
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So here we're just going to look at what the female is
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passing on, the alleles that she can create during her meiosis.
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So she can create wingless minus A, wingless plus B.
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These are both parental.
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They look like the ones that she already has
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or ones that she inherited from her parents.
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Or we can have recombinants or crossovers,
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and those would be wingless plus A and wingless minus B.
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And say we get some numbers here, 45, 40, 7, 8.
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So this is essentially precisely what
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we'd done before looking at two different phenotypes,
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but here we have a marker that we're
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looking at distance between the marker and the gene.
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So how many recombinants do we have here total?
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We have 15.
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And so we have 100 times 15 over 100,
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which equals a total of 15 centimorgans distance.
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Would it be possible to determine
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the alleles of the gametes without performing a cross?
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No.
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I mean, unless you could isolate the gametes themselves
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that they're generating, and that turns out
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to be a very difficult thing to do.
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But in essence, you have to do the crosses.
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So here we've done this cross, and we've actually
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identified a relationship between a marker, just
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this arbitrary piece of DNA that's not really
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doing anything but serving as a signpost in the genome,
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and some gene of interest.
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We're able to place this gene next to a particular marker
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of interest.
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And if we did this through the entire genome,
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if we interrogated every marker, we'll
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see that for most markers, wingless
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would be entirely unlinked.
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If it's on a different chromosome
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it would appear to be totally unlinked.
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And we can develop a relationship then
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with markers on the same chromosome, just how
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far it is away.
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Is it 40 centimorgans away?
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Is it 5 centimorgans away?
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Is it one centimorgan away?
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So it's completely linked so we can actually,
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again, place this in a precise location on the genome
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or in the genome.
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