Antonarakis S E, Oettgen P, Chakravarti A, Halloran S L, Hudson R R, Feisee L, Karathanasis S K
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Hum Genet. 1988 Nov;80(3):265-73. doi: 10.1007/BF01790095.
The genes coding for apolipoproteins A1, C3, and A4 (APOA1, APOC3, APOA4) are closely linked and tandemly organized within a 15-kilobase (kb) DNA segment on the long arm of human chromosome 11. The nucleotide variability of a 61-kb DNA segment containing these genes and their flanking sequences was studied by restriction analysis of a sample of 18 unrelated Northern Europeans using seven different genomic DNA probes. Eleven restriction site polymorphisms located within this DNA segment were used for haplotype analysis of 129 Mediterranean and 67 American black chromosomes. Estimation of the extent of nonrandom association between these polymorphisms indicated considerable linkage disequilibrium within the APOA1-APOC3-APOA4 gene cluster. Several haplotypes arose by recombination, and the rate of recombination within this gene cluster was estimated to be at least 4 times greater than that expected based on uniform recombination. The polymorphism information content of each of these polymorphisms, taken individually, ranges between 0.053 and 0.375, while that of their haplotypes ranges between 0.858 and 0.862. Therefore, DNA polymorphism haplotypes in the APOA1-APOC3-APOA4 gene cluster constitute a highly informative genetic marker on the long arm of human chromosome 11.
编码载脂蛋白A1、C3和A4（APOA1、APOC3、APOA4）的基因紧密相连，并在人类11号染色体长臂上一个15千碱基（kb）的DNA片段中呈串联排列。使用七种不同的基因组DNA探针，通过对18名无亲缘关系的北欧人样本进行限制性分析，研究了包含这些基因及其侧翼序列的61-kb DNA片段的核苷酸变异性。该DNA片段内的11个限制性位点多态性用于对129条地中海染色体和67条美国黑人染色体进行单倍型分析。对这些多态性之间非随机关联程度的估计表明，APOA1-APOC3-APOA4基因簇内存在相当程度的连锁不平衡。几种单倍型通过重组产生，该基因簇内的重组率估计至少比基于均匀重组预期的重组率高4倍。这些多态性各自的多态性信息含量在0.053至0.375之间，而它们单倍型的多态性信息含量在0.858至0.862之间。因此，APOA1-APOC3-APOA4基因簇中的DNA多态性单倍型构成了人类11号染色体长臂上一个信息丰富的遗传标记。
