Variant mapping of the Apo(B) at rich minisatellite. Dependence on nucleotide sequence of the copy number variations. Instability of the non-canonical alleles

Abstract

Because of Its variations in length, the AT rich Hyper-Varlable Region (HVR) of the 3′ end of the Apolipoprotein B gene Is used as a polymorphic maker In genetic studies. It contains a Sspl site In its repeated motif and we used this feature to precisely analyse the internal structure of the different alleles found at this locus In a Caucasian population. We performed total digestion on 194 alleles as well as Minisatellite Variant Repeat mapping (MVR mapping: partial digestion) on 54. The results show that the level of length variability (in copy number) of the 5′ end of this locus is at least two times higher than that of the 3′ end. This could be correlated with the difference in nucleotide sequence between the two parts of the HVR and suggests the dependence on the primary structure of the mechanism that produces length variability. A molecular model Is proposed to explain this result. Moreover, the sharp analysis of the minisatellite structure by the distribution of Sspl sites reveals differences between long and short alleles, indicating that in most cases, no recombination occurs between alleles of different sizes. Finally the rare alleles exhibit a non-canonical structure. These important points could explain the blmodal distribution of the frequencies of the alleles in the population. © 1993 IRL Press at Oxford University Press.