Henderson B G, Wenham P R, Ashby J P, Blundell G
Department of Clinical Biochemistry, Western General Hospital, Edinburgh, UK.
Clin Chem. 1997 Sep;43(9):1630-4.
Familial defective apolipoprotein (apo) B-100 (FDB), a condition that may give rise to hypercholesterolemia, is caused by mutations around codon 3500 of the apo B gene. We have compared the ability of three molecular-scanning techniques, heteroduplex analysis, single-strand conformation polymorphism (SSCP) analysis, and denaturing gradient gel electrophoresis (DGGE), to detect these mutations in a cohort of 432 hypercholesterolemic individuals. Heteroduplex analysis and DGGE detected 11 individuals with apo B mutations, 9 of whom were heterozygous for apo B R3500Q and 2 who were heterozygous for apo B R3531C. Whereas DGGE was able to distinguish between these two mutations, heteroduplex analysis was technically simpler and gave a higher sample throughput. In contrast, SSCP analysis detected only 7 of the R3500Q and none of the R3531C heterozygotes and was the most complex of the three techniques. We believe heteroduplex analysis to be the method of choice for screening large numbers of samples for FDB.
家族性载脂蛋白（apo）B-100缺陷（FDB）是一种可能导致高胆固醇血症的病症，由apo B基因第3500密码子附近的突变引起。我们比较了三种分子扫描技术，即异源双链分析、单链构象多态性（SSCP）分析和变性梯度凝胶电泳（DGGE），在432名高胆固醇血症患者队列中检测这些突变的能力。异源双链分析和DGGE检测到11名携带apo B突变的个体，其中9名是apo B R3500Q杂合子，2名是apo B R3531C杂合子。虽然DGGE能够区分这两种突变，但异源双链分析在技术上更简单，样本通量更高。相比之下，SSCP分析仅检测到7名R3500Q杂合子，未检测到R3531C杂合子，是三种技术中最复杂的。我们认为异源双链分析是筛查大量FDB样本的首选方法。
