LOD score too high - answers
dcurtis at hgmp.mrc.ac.uk
Thu Feb 9 05:31:33 EST 1995
> To remind you, when testing a disease against two closely-linked
>(to each other) markers, using MLINK, I got:
> 1 (disease), 2 lod = 4.7
> 1, 3 lod = 2.7
> 1, 2, 3 lod = 16!
> The consensus was (which makes perfect sense - I was simply ignorant)
>that the third value is "Ott's generalized lod score", which is based
>on the probability of ALL THREE LOCI BEING LINKED versus ALL 3 BEING
>UNLINKED. And I know that 2 of them are linked.
Sorry, I don't quite understand this. With MLINK, you generally only vary one
recombination fraction. To test the hypothesis of all linked against none
linked you'd have 1 - 0.0 - 2 - 0.0 - 3 against 1 - 0.5 - 2 - 0.5 - 3, which
would mean changing two intervals simultaneously. What you wanted to test was
1 - 0.0 - 2 - 0.0 - 3 against 1 - 0.5 - 2 - 0.0 - 3, i.e. the disease being
linked or unlinked against the two markers tightly linked to each other. The
mistake which might be relatively easy to make would be to test 1 - 0.0 - 2 -
0.0 - 3 against 1 - 0.0 - 2 - 0.5 - 3. This assumes the disease and first
marker are linked, and tests whether the second marker is linked to them.
That's not what you did is it? Otherwise, I don't quite see how you managed to
do what you say you did.
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