Extended haplotypes and linkage disequilibrium between 11 markers at the APOA1-C3-A4 gene cluster on chromosome 11

One hundred fifty-four unrelated French Caucasian subjects were typed for 11 RFLPs at or near the APOA1-C3-A4 gene cluster on the long arm of chromosome 11. All subjects belonged to families having lived in the Toulouse area (in the southwest of France) for over three generations. Allele frequencies for each RFLP were in agreement with previous studies in Caucasian populations for the APOA1/SstI marker. Pairwise linkage disequilibrium was determined. Among the 55 pairs studied, 30 are newly reported. Only three significant nonrandom associations were found: APOA1/MspI-3'APOC3/SstI, APOA1/MspI-3'APOA4/XbaI, and APOA4/DraI-APOA4/XbaI. Extended 11-marker haplotypes were constructed. Haplotype frequencies were estimated by the maximum-likelihood procedure and compared to expected frequencies calculated under the assumption of equilibrium. Among the 37 estimated haplotypes, seven containing at least four nonrandomly associated alleles showed markedly increased frequencies. These results, obtained in a geographically homogeneous population, confirm the existence of disequilibrium in the apolipoprotein cluster, but to a lower extent than previously reported in Caucasian populations, which were geographically more heterogeneous.