Cladistic analysis of haplotypes as an attempt to detect disease susceptibility.
We report the results of our analyses of the Genetic Analysis Workshop 12 simulated data set, using phylogenetic methods to reconstruct the history of haplotypes. We selected candidate gene 1 and 6, drawn from the isolate population. In a first step, haplotypes were inferred using family data. In a second step, cladistic approaches were performed to select the most parsimonious trees under various conditions of character state transformation and ancestral hypotheses, in order to check whether the affected status is more frequent in some clades than in others. Sites which are synapormophies of such clades can be viewed as candidate sites for the disease susceptibility. The method seems to be efficient for the candidate gene 1, but not for the candidate gene 6. Effects of the genetic model underlying the affection status are discussed, particularly dominance, penetrance, and, in the context of this simulated data, procedure followed to generate haplotypes. These preliminary results deserve further investigations.
Darlu
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INSERM U535, Bâtiment Gregory Pincus, 80 rue du General Leclerc, 94 276 Le Kremlin-Biêctre.
Génin
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D002874:Chromosome Mapping; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic; D010375:Pedigree; D019683:Penetrance; D012984:Software