Functional genomic dissection of rat blood pressure QTL

大鼠血压QTL的功能基因组解析

• 批准号: 6824447
• 负责人: BINA JOE
• 金额: $ 39.02万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6824447
• 关键词: alleles; blood pressure; computational biology; computer data analysis; dietary sodium; functional /structural genomics; gene expression; gene expression profiling; genetic strain; laboratory rat; linkage mapping; messenger RNA; microarray technology; nucleic acid sequence; nutrition related tag; oligonucleotides; polymerase chain reaction; quantitative trait loci

DESCRIPTION (provided by applicant): The purpose of this proposal is to identify the quantitative trait loci (QTL) that control blood pressure (BP) in the Dahl salt sensitive (S) rat. Multiple linkage analyses, each using the S rat as one of the parental strains, has resulted in the identification of at least 16 different QTL on the S rat genome that control blood pressure. The locations of 7 of these QTL on rat chromosomes 1, 2, 3, 5, 7, 9 and 10 have been confirmed and well defined by the construction of congenic rat strains. Each congenic strain contains a genomic segment from a relatively normotensive strain introgressed into the S rat genome and has significantly lower BP compared to the S rat. Congenic strains containing low BP QTL alleles on rat chromosomes 1 and 5 are the major focus for this proposal. These represent a unique research resource, by having their chromosomal locations delimited to precisely defined genomic intervals. Positional cloning of each of these QTL, while desirable, is a slow and laborious process. The overall strategy of this proposal is to couple congenic mapping of these BP QTL with gene expression analysis, thus providing the opportunity to expedite the process of BP QTL identification. We propose to address two questions using two approaches: Question (1) What is the identity of the BP causative gene within a QTL? Question (2) What is its action? Question 1 will be addressed by constructing and using a congenic-interval specific oligonucleotide array to identify differentially expressed genes between S rats and congenic rats. Question 2 will be addressed by using an already available rat genome chip, to identify the genes whose mRNA expression levels are affected by the causative gene.

描述（由申请人提供）：本提案的目的是鉴定控制Dahl盐敏感（S）大鼠血压（BP）的数量性状基因座（QTL）。多重连锁分析，每个使用S大鼠作为亲本品系之一，导致在S大鼠基因组上鉴定出至少16个不同的控制血压的QTL。其中7个QTL在大鼠1、2、3、5、7、9和10号染色体上的定位已通过构建同类大鼠品系得到证实和明确。每一个同源株含有一个基因组片段，从一个相对正常的应变渗入到S大鼠基因组，并具有显着较低的BP相比，S大鼠。在大鼠1号和5号染色体上含有低BP QTL等位基因的同类品系是该建议的主要焦点。这些代表了一个独特的研究资源，通过其染色体位置界定精确定义的基因组间隔。这些QTL中的每一个的定位克隆虽然是期望的，但是是缓慢且费力的过程。该方案的总体策略是将这些BP QTL的同源定位与基因表达分析相结合，从而为加快BP QTL的鉴定过程提供了机会。我们提出用两种方法来解决两个问题：问题（1）一个QTL中BP致病基因的身份是什么？问题（2）它的作用是什么？问题1将通过构建和使用同系间隔特异性寡核苷酸阵列来鉴定S大鼠和同系大鼠之间差异表达的基因来解决。问题2将通过使用现有的大鼠基因组芯片来解决，以识别其mRNA表达水平受致病基因影响的基因。