Linkage analysis - genehunting

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Linkage analysis - genehunting

• Thore Egeland

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Large pedigree one of 8 branches
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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

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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

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Markør 1
Markør 2
Main idea Assume A gives disease and that we
observe Marker 2. If ?0, then all affected
children in this family have B and all unaffected
b.
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lod-score

• likelihood of data if loci are linked (? lt 0.5)
  likelihood of data if loci are
  unlinked (? 0.5)

LR
LRLikelihood ratio Zlog(LR) lod-score.
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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?

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lod-scores are additive
0.1

0.5
Total lod score
0.6
Assumptions?
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Example

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

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lod score 1.5

• 101.532
• "The data is 32 times more likely assuming
  linkage".