Carr F J, Negrin C D, Clark J S, Graham D, McBride M W, Anderson N W, Dominiczak A F
Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow.
Scott Med J. 2002 Feb;47(1):7-9. doi: 10.1177/003693300204700104.
The localisation of quantitative trait loci (QTL) is the first step towards gene identification. This is then verified by the construction of reciprocal congenic strains. The hypertensive SHRSP and normotensive WKY strains were used in a speed congenic approach to confirm the existence of a QTL on rat chromosome 2. Systolic baseline and salt loaded blood pressures were measured by radiotelemetry. Transfer of the chromosome 2 blood pressure QTL region from WKY into an SHRSP background significantly reduced blood pressure, with the increased significance at the salt loaded period, compared to the SHRSP. The reciprocal congenic blood pressure showed a significantly increased baseline systolic pressure compared to the WKY, with no change in significance at the salt loaded period. Thus we have successfully captured a gene(s) which contribute to blood pressure regulation in both congenic strains. This will facilitate further positional cloning of the causative genes first in this model and then in human essential hypertension.
数量性状基因座(QTL)的定位是基因识别的第一步。然后通过构建 reciprocal congenic 品系来进行验证。高血压的 SHRSP 和正常血压的 WKY 品系被用于快速同源导入方法,以确认大鼠 2 号染色体上一个 QTL 的存在。通过无线电遥测法测量收缩压基线和盐负荷血压。将 2 号染色体血压 QTL 区域从 WKY 转移到 SHRSP 背景中,与 SHRSP 相比,显著降低了血压,在盐负荷期这种显著性增加。reciprocal congenic 血压与 WKY 相比,基线收缩压显著升高,在盐负荷期显著性没有变化。因此,我们成功捕获了一个在两个同源导入品系中都有助于血压调节的基因。这将有助于首先在该模型中,然后在人类原发性高血压中进一步对致病基因进行定位克隆。