PEDIGREE ANALYSIS OF HYPERTENSION MARKERS

原发性高血压是一种病因不明的多因素疾病， 对心血管疾病的死亡和残疾有很大影响。 影响个体健康的基因的识别和表征 患高血压的风险可以进行早期干预， 也许，预防或治愈。家系资料的遗传分析 然而，高血压很可能是缺乏信息或相互矛盾的。 因为这种疾病的多因素性质。 使用统计学和分子遗传学相结合的方法，我们 建议识别和描述影响五个基因的主要基因 高血压的生化标志物(心钠素水平、 红细胞钠转运和尿激肽释放酶的三项标志物 水平)，使用获得的超过900个家系的人口的数据 这些是狒狒。狒狒是一种成熟的动物模型，可用于研究 影响心血管疾病的遗传因素。我们将首先表演 分离分析以确定影响这五个基因的主要基因 中间表型。定位并确定(潜在的)专业的特征 基因，我们将使用数据进行连锁和测量的基因分析 在分子遗传标记方面。我们将为五个人开发DNA标记 候选基因座和900种纯系狒狒满足后者 目标。另外39个生化和分子的基因分型数据 标记也将可用于连锁和测量的基因型 分析。 最后，由于这五种中间表型与 不同的血压调节系统，我们将使用多变量 用遗传分析方法检验(潜力)之间的交互作用 影响血压的主要基因。这些结果可能会提供必要的 关于涉及到的基本细胞机制的信息 血压调节的基因控制。几位研究人员也 已经发现高血压危险因素之间相互作用的证据 和动脉粥样硬化。我们已经在我们的狒狒身上发现了主要的基因 几种脂蛋白表型的人群，这些表型是高血压的危险因素 动脉硬化。因此，我们有一个独特的机会来估计 遗传因素对高血压和高血压病的交互作用 动脉粥样硬化可能导致心血管疾病的风险。 这些遗传分析应该特别强大，因为 混杂的环境因素，如饮食，已经在我们的 纯正的狒狒聚居地。

Essential hypertension is a multifactorial disease of unknown etiology that contributes significantly to cardiovascular death and disability. Identification and characterization of genes that affect an individual's risk of developing hypertension could allow for early intervention and, perhaps, prevention or cure. Genetic analyses of family data on hypertension, however, have been uninformative or contradictory, probably because of the multifactorial nature of this disease. Using a combination of statistical and molecular genetic approaches, we propose to identify and characterize major genes that affect five biochemical markers of hypertension (atrial natriuretic peptide levels, three markers of erythrocyte sodium transport, and urinary kallikrein levels), using data obtained on a population of more than 900 pedigreed baboons. The baboon is well-established animal model for the study of genetic factors affecting cardiovascular disease. We first will perform segregation analyses to identify major genes that affect the five intermediate phenotypes. To locate and characterize the (potential) major genes, we will perform linkage and measured genotype analyses, using data on molecular genetic markers. We will develop DNA markers for five candidate loci and type 900 pedigreed baboons to meet this latter objective. Genotypic data on an additional 39 biochemical and molecular markers also will be available for use in the linkage and measured genotype analyses. Finally, as these five intermediate phenotypes are associated with different blood pressure regulatory systems, we will use multivariate genetic analysis methods to test for interaction among the (potential) major genes affecting blood pressure. Theses results may provide essential information in regard to the basic cellular mechanisms involved in the genetic control of blood pressure regulation. Several researchers also have found evidence of interactions between risk factors of hypertension and atherosclerosis. We already have identified major genes in our baboon population for several lipoprotein phenotypes that are risk factors for atherosclerosis. Thus, we have a unique opportunity to estimate the effects of interactions between genetic factors for both hypertension and atherosclerosis that may contribute to risk of cardiovascular disease. These genetic analyses should be especially powerful because the effects of confounding environmental factors, such as diet, have been minimized in our pedigreed baboon colony.