Garrett M R, Dene H, Walder R, Zhang Q Y, Cicila G T, Assadnia S, Deng A Y, Rapp J P
Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, Ohio 43614-5804 USA.
Genome Res. 1998 Jul;8(7):711-23. doi: 10.1101/gr.8.7.711.
An F2 population (n = 151) derived from Dahl salt-sensitive (S) and Lewis rats was raised on a 8% NaCl diet for 9 weeks and analyzed for blood pressure quantitative trait loci (QTL) by use of a whole genome scan. Chromosomes 5 and 10 yielded lod scores for linkage to blood pressure that were significant; chromosomes 1, 2, 3, 8, 16, 17, and 18 gave lod scores suggestive for linkage. Chromosome 7 gave a significant signal for heart weight with a lesser effect on blood pressure. Congenic strains were constructed by introgressing Lewis low-blood-pressure QTL alleles for chromosomes 1, 5, 10, and 17 into the S genetic background. Congenic strains for chromosomes 1, 5, and 10 had significantly lower blood pressure than S, proving the existence of QTL on these chromosomes, but the chromosome 17 congenic strain failed to trap a contrasting QTL allele. The QTL allele increasing blood pressure originated from S rats for all QTL except those on chromosomes 2 and 7 in which the Lewis allele increased blood pressure. Interactions between each QTL and every other locus in the genome scan yielded significant interactions between chromosomes 10 and 4, and between chromosomes 2 and 3.
将来自 Dahl 盐敏感(S)大鼠和 Lewis 大鼠的 F2 群体(n = 151)饲养在含 8%氯化钠的饮食中 9 周,并通过全基因组扫描分析血压数量性状位点(QTL)。第 5 号和第 10 号染色体产生了与血压连锁的显著 lod 分数;第 1、2、3、8、16、17 和 18 号染色体给出了提示连锁的 lod 分数。第 7 号染色体对心脏重量给出了显著信号,对血压的影响较小。通过将第 1、5、10 和 17 号染色体的 Lewis 低血压 QTL 等位基因导入 S 遗传背景构建了近交系。第 1、5 和 10 号染色体的近交系血压显著低于 S 系,证明了这些染色体上存在 QTL,但第 17 号染色体的近交系未能捕获到对比的 QTL 等位基因。除第 2 和第 7 号染色体上 Lewis 等位基因会升高血压外,所有 QTL 中升高血压的 QTL 等位基因均源自 S 大鼠。基因组扫描中每个 QTL 与其他位点之间的相互作用在第 10 号和第 4 号染色体之间以及第 2 号和第 3 号染色体之间产生了显著的相互作用。