GENETICS OF CEREBROVASCULAR DISEASE

拟议工作的总体目标是确定和 参与发病机制的遗传位点的表征 中风 这些研究将在以下动物模型中进行： 基因决定的高血压脑血管病， 人类疾病的许多特征，即中风倾向， 自发性高血压大鼠（SHRSP）。 疾病的解释- 该模型中的相关基因将为后续研究提供基础。 人类的研究。 拟议研究的相关性得到证明 中风作为公共卫生问题的重要性。 和以前一样， 高血压遗传学的相关工作，匿名和 序列特异性标记将被用于定量作图。 SHRSP与中风病患者杂交F2的性状位点， 抵抗性SHR，这是一种使我们能够避免血压升高的策略， 分析中的一个混淆因素 因为基因相近 在两种菌株之间，将特别努力 开发信息性遗传标记。 一旦一个位点被确定， 通过经典遗传（同源）和 将采用分子（定位克隆）方法。

The general objective of the proposed work is the identification and characterization of genetic loci that are involved in the pathogenesis of stroke. The studies will be carried out in an animal model of genetically determined hypertensive cerebrovascular disease, that shares many features with the human disease, viz. the stroke-prone, spontaneously hypertensive rat (SHRSP). Elucidation of disease- associated genes in this model will provide the basis for subsequent studies in humans. The relevance of the proposed studies is evidenced by the importance of stroke as public health issue. As in previous, related work on the genetics of hypertension, both anonymous and sequence-specific markers will be used for the mapping of quantitative trait loci in F2 hybrids derived from cross-breeding SHRSP with stroke- resistant SHR, a strategy that will allow us to avoid blood pressure as a confounding factor in the analysis. Because of the genetic proximity between the two strains, special efforts will be directed towards the development of informative genetic markers. Once a locus is identified, further characterization by both classical genetic (congenics) and molecular (positional cloning) approaches will be pursued.