A modifying locus for familial adenomatous polyposis may be present on chromosome lp35-p36

Abstract

Mutations of the APC gene cause familial adenotnatous polyposis (FAP) in humans and multiple intestinal neoplasia (Mm) in laboratory mouse strains. A dominant modifying gene (Momi), which partially suppresses the nun phenotype, has been mapped to mouse chromosome 4. This region is syntenic with human chromosome lp3S-p36. The phospholipase A2 (Pla2s) locus is an excellent candidate for Morni and the equivalent human locus PLA2G2A is found on chromosome lp3S. It does not necessarily follow, however, than any modifier of mouse polyposis also influences human disease. In order to test whether a locus on ip modifies FAP, subjects from 28 FAP families have been typed at microsatellite loci on this chromosome ann. The severity of their duodenal polyposis has also been assessed by endoscopy. Pedigree (lod score) linkage analysis found no evidence of a simple, dominant modifying gene, comparable with the action of Monzl in inbred mouse strains. Given the more complex genetic and environmental interactions likely to exist in outbred human populations, it is probably more appropriate to use tests which do not specify a mode of inheritance. Using these methods of analysis, the data suggest that a locus on chromosome lp35-p36 may influence the severity of duodenal FAR.