Rapp J P, Garrett M R, Deng A Y
Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, Ohio 43614-5804, USA.
J Clin Invest. 1998 Apr 15;101(8):1591-5. doi: 10.1172/JCI2251.
Previously we presented suggestive evidence from an F2 segregating population for an interaction on blood pressure (BP) between quantitative trait loci (QTL) on rat chromosomes (Chr) 2 and 10. To prove the existence of such an interaction, we developed congenic strains for Chr 2 and 10 by introgressing the low BP QTL alleles into the Dahl salt-sensitive (S) strain. A double congenic strain was also constructed with both the Chr 2 and 10 low BP QTL alleles on the S background. The four strains (S, Chr 2 congenic, Chr 10 congenic, and Chr 2/10 double congenic) were studied for BP response to increased salt intake. An analysis of variance showed significant main effects of Chr 2, Chr 10, and a significant interaction between Chr 2 and 10 on BP and heart weight (all P < 0.0001). The interaction accounted for 24 mmHg of BP and 79 mg of heart weight. Thus, the discovery and proof of epistatic interactions are clearly critical to understanding the genetics of blood pressure.
此前，我们在一个F2分离群体中展示了提示性证据，表明大鼠2号和10号染色体上的数量性状基因座（QTL）之间存在血压（BP）相互作用。为了证明这种相互作用的存在，我们通过将低BP QTL等位基因渗入到Dahl盐敏感（S）品系中，培育出了2号和10号染色体的近交系。还构建了一个双近交系，其在S背景上同时带有2号和10号染色体的低BP QTL等位基因。研究了这四个品系（S、2号染色体近交系、10号染色体近交系和2/10号染色体双近交系）对盐摄入量增加的血压反应。方差分析显示，2号染色体、10号染色体对血压和心脏重量有显著的主效应，且2号和10号染色体之间存在显著的相互作用（所有P<0.0001）。这种相互作用导致血压升高24 mmHg，心脏重量增加79 mg。因此，上位性相互作用的发现和证明对于理解血压遗传学显然至关重要。
