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Linkage analysis - genehunting

Linkage analysis - genehunting. Thore Egeland. Large pedigree; one of 8 branches:. What's linkage analysis. “... only method that allows mapping of genes, including disease genes, that are detectable only as phenotypic traits ” Thompson & Thompson, p.118, 6 ed. Phase known.

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Linkage analysis - genehunting

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  1. Linkage analysis - genehunting Thore Egeland

  2. Large pedigree; one of 8 branches:

  3. What's linkage analysis “...only method that allows mapping of genes, including disease genes, that are detectable only as phenotypic traits” • Thompson & Thompson, p.118, 6 ed

  4. Phase known • Children may inherit (A,B), (A,b),(a,B) or (a,b) from the father • What is the statistical distribution of these haplotypes in the children • Depends on distance between the markers

  5. Markør 1 Markør 2 Main idea: Assume A gives disease and that we observe Marker 2. If θ=0, then all affected children in this family have B and all unaffected b.

  6. lod-score likelihood of data if loci are linked (θ < 0.5) likelihood of data if loci are unlinked (θ =0.5) LR= LR=Likelihood ratio Z=log(LR) lod-score.

  7. lod-score. Conventions • lod-score above 2: linkage for X • lod-score above 3: autosomal-linkageCorresponds to p-verdi below 0.0001 • Why do we require this extreme p-value?

  8. lod-scores are additive 0.1 + 0.5 Total lod score 0.6 Assumptions?

  9. Example • A lod score of 1.5 has been reportedWhat does that mean?

  10. lod score 1.5 • 101.5=32 • "The data is 32 times more likely assuming linkage".

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