Functional genomic dissection of rat blood pressure QTL

大鼠血压QTL的功能基因组解析

• 批准号: 6914975
• 负责人: BINA JOE
• 金额: $ 38.02万
• 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/6914975
• 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(申请人提供)：本建议的目的是确定控制血压的数量性状基因座(QTL)在达尔盐敏感(S)大鼠。多个连锁分析，每个以S大鼠作为亲本品系之一，已经在S大鼠基因组上识别出至少16个控制血压的不同QTL。其中7个QTL在大鼠第1、2、3、5、7、9和10号染色体上的位置已经被同源品系的构建所证实和很好地确定。每个同源品系都包含一个来自相对正常血压品系的基因组片段，该片段导入到S大鼠的基因组中，并且与S大鼠相比，其BP显着降低。在大鼠1号和5号染色体上含有低BP QTL等位基因的同源菌株是这一提议的主要焦点。它们代表着一种独特的研究资源，它们的染色体位置被界定为精确定义的基因组间隔。这些QTL的位置克隆虽然是可取的，但却是一个缓慢而费力的过程。这一建议的总体策略是将这些BP QTL的同源定位与基因表达分析结合起来，从而为加快BP QTL的鉴定进程提供了机会。我们建议用两种方法来解决两个问题：问题(1)在QTL中BP致病基因的同一性是什么？问题(2)它的行动是什么？问题1将通过构建和使用同源区间特异性寡核苷酸阵列来鉴定S大鼠和同源大鼠之间的差异表达基因。问题2将通过使用已有的大鼠基因组芯片来解决，以确定其mRNA表达水平受致病基因影响的基因。