ApoB gene MspI RFLP in exon 26 changes amino acid 3611 from Arg to Gln

An apolipoprotein B gene MspI RFLP was identified by the use of a probe to a portion of the 3' end of the gene. By Southern blotting analysis after digestion with MspI, this probe detected either a 9 kb or a 2.6 kb fragment. Family studies showed that these corresponded to alleles that segregated in a simple Mendelian fashion. The minor allele (9.0 kb) had a frequency of approximately 12% in an unrelated Caucasian population. Restriction mapping showed that the minor allele was due to the loss of an MspI site in exon 26. Sequencing of both alleles in the region containing the polymorphic MspI site revealed a single-base pair alteration which abolished the MspI site at codon 3611 of the mature apoB protein. In the major allele, this codon is CGG, which specifies Arg; whereas in the minor allele, it was CAG, which codes for Gln.