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The internal structure of different alleles of the minisatellite present at the 3′ end of the apolipoprotein B (ApoB) gene has been analysed by different approaches including sequencing. The repeat unit arrangements of the minisatellite on 570 chromosomes belonging to European and African populations were thus determined. It was possible to group the alleles using this structural criterion much more clearly than by the number of repeat units which can in some cases be misleading in case-control genetic epidemiological studies using such DNA sequences as markers. We were thus able to define five types (a to e) of alleles and their subtypes and to recognize clearly those which are, respectively, specific of the African and Caucasian populations. A phylogeny of the different alleles found in all human populations could also be deduced by this approach. The different putative mutational events leading from one type, or subtype, to the other were simply determined as point mutations, expansion/contraction and conversion events. Sequencing of one chimpanzee's allele suggested that the ApoB minisatellite was present before divergence between great apes and humans. It was determined also that a particular ApoB gene haplotype was in linkage disequilibrium with the minisatellite (a) type of alleles. This and the observation that the potential scaffold attachment regions (SAR) and topoisomerase II binding sites present in this minisatellite have a different distribution between the Caucasian and the African specific alleles suggest that the minisatellite could be involved in the epidemiology of coronary diseases.

human molecular genetics

Structural Analysis of the Minisatellite Present at the 3′ end of the Human Apolipoprotein B Gene: New Definition of the Alleles and Evolutionary Implications