GENETICS OF CEREBROVASCULAR DISEASE

拟议工作的总体目标是确定和 与发病有关的遗传位点的特征 中风的可能性。这些研究将在一个动物模型中进行。 基因决定的高血压脑血管疾病，分享 人类疾病的许多特征，即。容易中风的人， 自发性高血压大鼠(SHRSP)。疾病的澄清- 该模型中的相关基因将为后续研究提供基础 在人体上的研究。拟议研究的相关性得到了证明。 中风作为公共卫生问题的重要性。和之前一样， 关于高血压遗传学的相关工作，包括匿名和 序列特异性标记将用于定量的作图 SHRSP与中风病杂交F2代的性状基因座 抵抗型自发性高血压，这一策略将允许我们避免血压 分析中的一个混杂因素。因为基因上的接近 在这两个菌株之间，将特别努力 发展信息丰富的遗传标记。一旦确定了一个轨迹， 经典遗传(遗传)和遗传的进一步表征 将采用分子(位置克隆)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.