POSITIONAL CLONING OF BLOOD PRESSURE QTL

描述(申请人的逐字描述)： 众所周知，人类是一种复杂的特征，其遗传成分受 很多基因。这些基因的身份尚不清楚。要识别这多个 控制血压的基因有遗传性高血压动物模型 是在老鼠体内发育的。我们的总体目标是使用 DAHL盐敏感型(S)高血压大鼠基因定位 血压的变化。与所有动物模型系统一样，预计 在老鼠身上获得的信息将使人们对人类的状况有更深入的了解。 遗传分析采用识别大鼠染色体区域的形式 连锁分析对血压的影响。血压的存在 数量性状基因座(QTL)是通过构建同源基因来确认的 其中低血压等位基因被替换到基因上的菌株 S大鼠的背景。含有该QTL的同源染色体片段为 然后通过几次同源菌株的迭代逐渐减少 构造，直到该区域足够小，可以对 导致血压的基因。后者需要约0.3的同源区域 厘米摩根。这样一个地区的实物地图将被准备好，整个 该地区将进行DNA测序。靶区中的新的和已知的基因将是 通过序列分析鉴定。候选基因将被寻找基于 S大鼠已知或演绎的功能和/或表达的差异 以及同源菌株。 上述分析是对大鼠染色体1、5、 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.