GENETIC DETERMINANTS OF HYPERTENSION

该项目的主要目标是利用关于小鼠高血压的信息，生成项目I在这个专门研究中心(SCOR)收集的关于人类人群中高血压的可检验假说。具体地说，我们预计(A)我们使用小鼠模型产生的数量性状基因座(QTL)将预测在人类中测试的染色体区域，(B)我们在小鼠中发现的基因相互作用将预测在人类中测试的基因交互作用，以及(C)我们通过表达或序列差异找到的候选基因将预测在人类中测试的候选基因。为了在小鼠模型中发现所有可能的血压基因，我们将使用遗传多样性的小鼠品系进行另外五个QTL杂交。利用多种技术的组合，我们将缩小QTL的范围，重点放在小鼠Chr1、11和18上发现的与项目1重点关注的人类高血压QTL同源的QTL。此外，我们还将测试候选基因的表达和序列差异。到拨款的第三年，我们应该有可用的含有高比例小鼠基因的微阵列，我们将利用这些微阵列来寻找候选基因的表达差异。

The major goal of this project is to use information about hypertension in mice to generate testable hypotheses about hypertension in the human populations gathered by Project I in this Specialized Center of Research (SCOR). Specifically, we expect that (a) the quantitative trait loci (QTL) that we generate using the mouse model will predict chromosomal regions to test in humans, (b) the gene interactions we find in the mouse will predict gene interactions to test in humans, and (c) the candidate genes we find by expression or sequence differences will predict candidate genes to test in humans. To find the full range of possible blood pressure genes in the mouse model, we will carry out five additional QTL crosses using genetically diverse mouse strains. Using a combination of techniques, we will narrow the QTL regions focusing on those QTL found on mouse Chr 1, 11, and 18, which are homologous to human hypertension QTL that the focus of Project 1. In addition, we will test candidate genes for expression and sequence differences. By year 3 of the grant, we should have available microarrays with a high proportion of mouse genes, and we will use these in the search for expression differences in candidate genes.