Using mutagenic polymerase chain reaction primers to detect carriers of familial defective apolipoprotein B-100.

Familial defective apolipoprotein (apo) B-100 is a genetic trait characterized by an Arg----Gln substitution in position 3500 of the apo B sequence. This genetic defect is associated with greatly increased concentrations of plasma cholesterol and may thus increase the risk of developing premature atherosclerotic disease. We describe here the use of mutagenic polymerase chain reaction primers, which greatly facilitate identification of carriers of this mutation. Moreover, we demonstrate that this method may also be used for determining the phase between two polymorphic sites. Using apo B-100 as an example we located on different chromosomes the defect in codon 3500 and a mutation in codon 3611, which produces another Arg----Gln change in the encoded apo B-100 amino acid sequence, in two probands heterozygous for both mutations.