POSITIONAL CLONING OF BLOOD PRESSURE QTL

描述（申请人逐字描述）：原发性高血压， 众所周知，人类是一种复杂的性状，其遗传成分受到以下因素的影响： 许多基因。这些基因的身份是未知的。为了识别这些多个 控制血压的基因遗传性高血压的动物模型 是在老鼠身上开发的。我们的总体目标是利用 Dahl盐敏感性高血压大鼠基因的研究 血压的变化。与所有动物模型系统一样， 从老鼠身上获得的信息将有助于了解人类的状况。 遗传分析的形式是识别大鼠染色体的区域 通过连锁分析影响血压。血压的存在 数量性状基因座（QTL）是通过构建同源 其中低血压等位基因被置换到遗传上的菌株， 老鼠的背景含有QTL的同源染色体片段是 然后通过几次同类菌株的迭代逐渐减少 构建，直到该区域足够小以用于定位克隆所述重组质粒。 高血压基因后者需要约0.3的同源区域 厘摩根将绘制这一区域的实物地图， 将进行DNA测序。目标区域中的新基因和已知基因将被 通过序列分析鉴定。候选基因将根据 S大鼠之间已知或推断的功能和/或表达差异 和同类菌株。 上述分析是针对大鼠1、5号染色体上的血压QTL提出的， 7和10。

DESCRIPTION (the applicant's description verbatim): Essential hypertension in humans is known to be a complex trait with a genetic component influenced by many genes. The identity of these genes is unknown. To identify these multiple genes controlling blood pressure animal models of genetic hypertension have been developed in the rat. Our overall objective is to use the Dahl-salt-sensitive (S) hypertensive rat to define the genes causing genetic variation in blood pressure. As with all animal model systems it is expected that information obtained in rats will give insight into the human condition. Genetic analysis takes the form of identifying regions of rat chromosomes influencing blood pressure by linkage analysis. The existence of blood pressure quantitative trait loci (QTL) is confirmed by the construction of congenic strains in which a low blood pressure allele is substituted onto the genetic background of the S rat. The congenic chromosomal segment containing the QTL is then progressively reduced by several iterations of congenic strain construction until the region is small enough for positional cloning of the blood pressure causing gene. The latter requires a congenic region of about 0.3 centiMorgans. Physical maps of such a region will be prepared and the entire region will be DNA sequenced. New and known genes in the target region will be identified through the sequence analysis. Candidate genes will be sought based on known or deduced function and/or differences in expression between S rats and the congenic strains. The above analysis is proposed for blood pressure QTL on rat chromosome 1, 5, 7, and 10.