Harrap S B
MRC Blood Pressure Unit, Western Infirmary, Glasgow, Scotland.
J Cardiovasc Pharmacol. 1988;12 Suppl 3:S99-109.
Numerous biochemical and physiological phenotypic differences exist between genetically normotensive and hypertensive rats. Only some of these differences, however, are likely to be related to the primary mechanisms causing high blood pressure. Others, and perhaps the majority, will be the result of either the secondary effects of hypertension or the result of incidental genetic differences between the strains that bear no relationship to the difference in blood pressure. Cosegregational analysis by cross-breeding normotensive and hypertensive strains permits the identification of phenotypes that are genetically linked to high blood pressure. However, cosegregational analyses are still prone to the confounding effects of hypertension per se, which can obscure important phenotypic traits and might even mimic Mendelian inheritance of phenotypes by producing qualitative shifts in gene expression. This paper discusses a longitudinal approach to genetic analysis designed to increase the sensitivity with which primary causes of high blood pressure are identified, by beginning the analysis during the development of high blood pressure. At this stage, phenotypic abnormalities causing blood pressure to rise are most likely to be present, and the blood pressure elevation is small so that the confounding effects of elevated arterial pressure are minimized.
基因正常血压大鼠和高血压大鼠之间存在许多生化和生理表型差异。然而，这些差异中只有一些可能与导致高血压的主要机制有关。其他差异，或许是大多数差异，将是高血压的继发效应或品系间偶然遗传差异的结果，而这些差异与血压差异无关。通过将正常血压品系和高血压品系进行杂交进行共分离分析，可以识别出与高血压存在遗传联系的表型。然而，共分离分析仍然容易受到高血压本身的混杂效应影响，这可能会掩盖重要的表型特征，甚至可能通过产生基因表达的定性变化来模拟表型的孟德尔遗传。本文讨论了一种纵向遗传分析方法，旨在通过在高血压发展过程中开始分析来提高识别高血压主要病因的敏感性。在此阶段，最有可能存在导致血压升高的表型异常，并且血压升高幅度较小，从而将动脉压升高的混杂效应降至最低。
