DETECTING FAMILIAL DEFECTIVE APOLIPOPROTEIN B-100 - 3 MOLECULAR SCANNING METHODS COMPARED

Familial defective apolipoprotein (apo) B-100 (FDB), a condition that may give rise to hypercholesterolemia, is caused by mutations around c odon 3500 of the apo B gene. We have compared the ability of three mol ecular-scanning techniques, heteroduplex analysis, single-strand confo rmation polymorphism (SSCP) analysis, and denaturing gradient gel elec trophoresis (DGGE), to detect these mutations in a cohort of 432 hyper cholesterolemic individuals. Heteroduplex analysis and DGGE detected 1 1 individuals with apo B mutations, 9 of whom were heterozygous for ap o B R3500Q and 2 who were heterozygous for apo B R3531C, Whereas DGGE was able to distinguish between these two mutations, heteroduplex anal ysis was technically simpler and gave a higher sample throughput. In c ontrast, SSCP analysis defected only 7 of the R3500Q and none of the R 3531C heterozygotes and was the most complex of the three techniques. We believe heteroduplex analysis to be the method of choice for screen ing large numbers of samples for FDB.