Apolipoprotein B: the Ag(a1/d) immunogenetic polymorphism coincides with a T-to-C substitution at nucleotide 1981, creating an Alu I restriction site.

Short cDNA fragments covering the entire coding region for apolipoprotein (apo) B have been cloned in the pING expression vector. A monoclonal antibody specific for the Ag(d) epitope on apo B has been used, together with the expressed apo B peptides, to locate this epitope to a stretch of 26 amino acids. Sequencing of this region from several genomic DNAs of known Ag(a1/d) genotype showed a single T-to-C substitution at nucleotide 1981, creating an Alu I restriction site and resulting in a val to ala residue change in the corresponding peptide (at position 591 in the mature protein). Southern blots, using the Alu I restriction endonuclease and a short probe for this region of the cDNA, showed perfect correspondence between the restriction fragment length polymorphism and the Ag(a1/d) immunochemical polymorphism in all 17 persons examined.