Waardenburg syndrome in man and splotch mutants in the mouse: a paradigm of the usefulness of linkage and synteny homologies in mouse and man for the genetic analysis of human congenital malformations.
The use of chromosomal segments with conserved homologous linkage groups found in different species provides one method of predicting the location of genes causing congenital malformations in man. For example, homology between man and mouse involves 241 homologous autosomal genes spread on 68 homologous chromosomal segments. In addition, the similarities of phenotypic expression of human congenital malformations and mouse mutations indicate the possible involvement of an homologous gene implicated during ontogeny of the two species. The identification of a single gene defect in the mouse and comparative mouse-human gene mapping provides therefore another approach for selecting candidate loci for inborn error of morphogenesis in man. Further molecular studies can then be performed to show that the loci are identical. The human Waardenburg syndrome and the splotch (Sp) mouse mutant represent the first example of the potential of this approach for the understanding of human congenital malformations at the molecular level.
Service d'Histologie, Embryologie et de Cytogénétique, Groupe Hospitalier Necker-Enfants Malades, Paris, France.
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D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D005801:Genes, Homeobox; D008040:Genetic Linkage; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010641:Phenotype; D017385:Sequence Homology; D014849:Waardenburg Syndrome / Q000235:genetics*