THE FAMILIAL ADENOMATOUS POLYPOSIS REGION EXHIBITS MANY DIFFERENT HAPLOTYPES

In the present study, we used five different polymorphic markers to co nstruct the haplotype at the adenomatous polyposis coli (APC) locus in families with familial adenomatous polyposis (FAP) and in the normal Italian population. Non-ambiguous haplotypes were reconstructed from 2 46 normal chromosomes and 65 FAP chromosomes. In the control populatio n, the four polymorphisms intragenic to APC gave rise to 16 haplotypes , the most common of which (II and XV) accounted for over 50% of all c hromosomes. In FAP patients, 13 haplotypes were found but their distri bution was not statistically different from normal subjects. Eighty co mplete chromosomal haplotypes (many fewer than the theoretical maximum of 208) for the five polymorphic sites assayed were observed in the c ontrol population, 35 being found in the FAP patients. We compared the distribution of these haplotypes within the two groups; no statistica lly significant differences between normal and FAP chromosomes were fo und. The elevated heterogeneity of FAP chromosomes was clearly confirm ed by the observation that 19 patients who carried one or other of the two most common APC mutations (nt 3183 and nt 3927) showed 18 differe nt haplotypes. On the basis of these results, we were not able to iden tify a founder FAP chromosome. Various mechanisms are presented to exp lain this observation.