PEDIGREE ANALYSIS OF HYPERTENSION MARKERS

原发性高血压是一种病因不明的多因素疾病， 对心血管死亡和残疾有很大的影响。 影响个体免疫功能的基因的鉴定和表征 发生高血压的风险可以允许早期干预， 也许是预防或治疗。 遗传分析的家庭数据， 然而，高血压可能没有提供信息或自相矛盾， 因为这种疾病的多因素性。 使用统计和分子遗传学方法的组合，我们 建议识别和表征影响五个主要基因， 高血压的生化标志物（心房利钠肽水平， 红细胞钠转运三项指标和尿激肽释放酶 水平），使用900多个血统的人口获得的数据 狒狒 狒狒是研究 影响心血管疾病的遗传因素。 我们首先要表演 分离分析，以确定影响五个主要基因 中间表型 定位和描述（潜在）专业 基因，我们将进行连锁和测量基因型分析，使用数据 分子遗传标记 我们将为五个人开发DNA标记 候选位点和900型纯种狒狒，以满足后者 objective. 另外39个生化和分子生物学的基因型数据 标记也将可用于连锁和测量基因型 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 遗传分析方法，以测试（潜在） 影响血压的主要基因 这些结果可以提供必要的 关于参与的基本细胞机制的信息， 血压调节的遗传控制。 一些研究人员还 发现了高血压危险因素之间相互作用的证据 和动脉粥样硬化。 我们已经确定了狒狒的主要基因 人群中的几种脂蛋白表型，这些表型是 动脉粥样硬化 因此，我们有一个独特的机会来估计 遗传因素对高血压和 动脉粥样硬化可能导致心血管疾病的风险。 这些基因分析应该特别强大，因为 在我们的研究中，混杂的环境因素，如饮食，已被最小化。 纯种狒狒群

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.