STRUCTURAL-ANALYSIS OF THE MINISATELLITE PRESENT AT THE 3'-END OF THEHUMAN APOLIPOPROTEIN-B GENE - NEW DEFINITION OF THE ALLELES AND EVOLUTIONARY IMPLICATIONS

The internal structure of different alleles of the minisatellite prese nt at the 3' end of the apolipoprotein B (ApoB) gene has been analysed by different approaches including sequencing. The repeat unit arrange ments of the minisatellite on 570 chromosomes belonging to European an d African populations were thus determined. It was possible to group t he alleles using this structural criterion much more clearly than by t he number of repeat units which can in some cases be misleading in cas e-control genetic epidemiological studies using such DNA sequences as markers. We were thus able to define five types (a to e) of alleles an d their subtypes and to recognize clearly those which are, respectivel y, specific of the African and Caucasian populations. A phylogeny of t he different alleles found in all human populations could also be dedu ced by this approach. The different putative mutational events leading from one type, or subtype, to the other were simply determined as poi nt mutations, expansion/contraction and conversion events. Sequencing of one chimpanzee's allele suggested that the ApoB minisatellite was p resent before divergence between great apes and humans. It was determi ned also that a particular ApoB gene haplotype was in linkage disequil ibrium with the minisatellite (a) type of alleles. This and the observ ation that the potential scaffold attachment regions (SAR) and topoiso merase II binding sites present in this minisatellite have a different distribution between the Caucasian and the African specific alleles s uggest that the minisatellite could be involved in the epidemiology of coronary diseases.