LOD score too high - answers

David Curtis 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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