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PETER REDDIEN: So let's get a LOD score.
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OK, so we'll put in our data.
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OK, so log base 10 of 0.75 over 2 cubed times
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0.25 over 2 for the first power over 0.25 to the fourth power.
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OK, so we get a value here of 0.23.
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OK, so now to your question, what
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do you do with the LOD score, this
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is a statistical test we're trying
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to utilize to assess linkage.
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And by convention, a threshold for a LOD score
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has been set such that if your score is above that threshold,
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your probability of concluding linkage incorrectly
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is less than 0.05, OK.
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And that threshold is a LOD score
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of greater than or equal to 3.
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OK.
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And that threshold is set-- it will depend depending
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upon the size of the genome, the number of chromosomes and so on
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across species.
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But this is a threshold that's been
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set by convention corresponds to about 1,000 to 1 odds
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or exactly 1,000 to 1 odds.
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This is a threshold that has been set that will give you
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significance for linkage.
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OK, so what do we conclude with our LOD score, the 0.23?
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Can we conclude that they are linked?
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No, so we don't have enough data.
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So we cannot conclude linkage.
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We tested for linkage at this theta.
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We could test at other thetas, and you get a different LOD
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score.
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But we selected a theta that gave us
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our best chance of seeing linkage,
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because we used a theta based on the data.
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So we're not going to do better if we try other thetas.
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Now you can see that this was a pretty large number
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of offspring, but we're nowhere near our threshold of 3.
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So how would we ever get significant linkage
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for our markers in a diseased gene, OK.
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What do you guys think?
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You could go around testing families
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every time you see a disease crop up,
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and you're often going to be in this situation.
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So how would we ever get a significant statistical test
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here with data that would allow us to move forward and look
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at a particular region of the chromosome
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where we think our gene is?
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Any ideas moving beyond the situation of this problem
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and just thinking of general?
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Do it across multiple families.
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OK, so that's what's done.
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So now you can add the data from families.
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Because of the property of logarithms,
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you can just add the LOD scores from individual families,
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or you can include all the informative meiosis
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in one individual calculation, whichever you prefer.
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OK.
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All right, so that's what's done.
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Now there's one more thing I want
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to mention before going to part two, which
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is phase unknown, which is I want to emphasize something
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I just mentioned once we went through this,
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but you want to use the data from any informative meiosis
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across the pedigree.
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OK, so we use want to use all the generations
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in your pedigree that have informative meiosis.
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You might see a generation at the end
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and, sort of, your attention get focused on that.
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But if the pedigree is long, there
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could have been informative meiosis
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higher up in the pedigree if you have data
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from those generations.
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