Discovering the Genetic Basis of Hypertension

发现高血压的遗传基础

• 批准号: 7302822
• 负责人: ELEAZAR ESKIN
• 金额: $ 6.82万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7302822
• 关键词: Internet; bioinformatics; biotechnology; blood tests; cardiovascular disorder risk; chromogranins; clinical research; computational biology; computer program /software; family genetics; genetic markers; genetic screening; genetic susceptibility; human genetic material tag; human subject; hypertension; molecular biology information system; pharmacogenetics; single nucleotide polymorphism

DESCRIPTION (provided by applicant): With the completion of the human genome project, much of the progress in understanding the genetic basis of disease relies on computational analysis of genomic data. Some of the most useful data for this analysis is human variation data. This data consists of information on the variation in genes associated with a disease for a population of individuals. Understanding the relation between variation and disease is a fundamental challenge, which can shed light on the genetic basis and mechanisms of human disease. This challenge spans three research fields: genetics, bioinformatics and medicine. Understanding the genetic basis of disease involves two steps. First, we must determine the functional variants in each gene locus that is linked to the disease and the effect of functional variants on the regulation and gene products of the gene. Second, we must understand how these intermediate phenotypes affect disease outcomes. Using this information, we can identify subtypes of the disease which are candidates for different drug response. In this proposal we outline our approach for this problem and propose to build tools for modeling the function of variation in a gene locus, correlating the intermediate phenotypes to disease outcomes and identifying subtypes of the disease based on genetic variants. The core of our approach involves haplotype analysis and we leverage previously developed tools for this analysis. We demonstrate initial results over the Chromogranin A locus. The disease focus of this proposal is hypertension and the tools will be applied to the large amount of data collected at UCSD through the pharmacogenomics project. This proposal contains of an extensive training plan for Eleazar Eskin including courses at UCSD in order for him to obtain the necessary background in hypertension and genetics for the project. Daniel O'Connor and Nicholas Schork will mentor Eleazar throughout the project. This training and mentoring will put Eleazar in a position to have his research have a larger impact in medicine. This research is relevant to public health because it attempts to understand the relation between an individual's genetic variation and disease outcomes. Identification of the variants that are implicated in complex disease is the first step in the ultimate goal of tailoring treatments to an individual's genetics.

描述（由申请人提供）： 随着人类基因组项目的完成，理解疾病的遗传基础的许多进步依赖于基因组数据的计算分析。该分析的一些最有用的数据是人类变异数据。该数据包含有关与个体人群相关的基因变异的信息。了解变异与疾病之间的关系是一个基本挑战，它可以阐明人类疾病的遗传基础和机制。这项挑战涵盖了三个研究领域：遗传学，生物信息学和医学。了解疾病的遗传基础涉及两个步骤。首先，我们必须确定每个基因基因座中与疾病以及功能变体对基因调节和基因产物的影响的功能变异。其次，我们必须了解这些中间表型如何影响疾病结果。使用这些信息，我们可以鉴定该疾病的亚型，这些亚型是不同药物反应的候选者。 在此提案中，我们概述了解决此问题的方法，并建议构建建模基因基因座变异功能的工具，将中间表型与疾病结局相关联，并基于遗传变异鉴定疾病的亚型。我们方法的核心涉及单倍型分析，我们利用了以前开发的该分析工具。我们证明了铬烷蛋白A基因座的初始结果。该提案的疾病重点是高血压，工具将通过药物基因组学项目应用于UCSD收集的大量数据。 该提案包含针对Eleazar Eskin的广泛培训计划，其中包括UCSD的课程，以便他获得该项目的高血压和遗传学的必要背景。丹尼尔·奥康纳（Daniel O'Connor）和尼古拉斯·舒克（Nicholas Schork）将在整个项目中指导Eleazar。这种培训和指导将使Eleazar的研究对医学产生更大的影响。 这项研究与公共卫生有关，因为它试图了解个人的遗传变异与疾病结果之间的关系。鉴定与复杂疾病有关的变体是将治疗方法定制为个人遗传学的最终目标的第一步。