FINE GENETIC MAPPING OF BLOOD PRESSURE QTL

血压QTL精细遗传作图

• 批准号: 6302400
• 负责人: JOHN P RAPP
• 金额: $ 19.94万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6302400
• 关键词: blood pressure; disease /disorder model; familial hypertension; genetic markers; genetic strain; genome; laboratory rat; linkage mapping; molecular cloning; molecular genetics; phenotype; quantitative trait loci

The overall objective of my work is to identify the quantitative trait loci (QTL) controlling blood pressure in the rat. A paradigm for doing this has the following components: (a) identify genetic markers that cosegregate with blood pressure in the rat; (b) develop linkage maps at a resolution of 5-10 centiMorgans (cM) for the rat chromosomal regions involved in order to obtain a crude localization of the blood pressure QTL by interval mapping; (c) produce congenic strains for each low-blood- pressure QTL allele on the genetic background of the inbred Dahl salt- hypertension sensitive (S) rat; d) develop rat linkage maps at a resolution of 1-2 cM for QTL-containing chromosomal regions; e) refine the genetic mapping of blood pressure QTL by substituting progressively smaller and smaller regions of chromosome containing the low-blood- pressure QTL allele on the S genetic background; f) and ultimately prepare physical maps for at least one such QTL region and attempt positional cloning. The present proposal concentrates on the production of dense genetic maps and the production of congenic strains for blood pressure QTL on rat chromosomes 1, 2 and 10, and the production of congenic substrains for fine genetic mapping of the blood pressure QTL on these chromosomes. Preparation of first order maps and localization of the blood pressure QTL on chromosomes 9 and 13 are also proposed. A full genome scan of an population derived from S and Lewis rats will be performed to complete the description of this particularly informative cross which has so far yielded four blood pressure QTL accounting for 105 mmHg. The proposed studies are important because they will: (a) provide genetic markers that can be used to study genetic (essential) hypertension in humans; (b) provide congenic strains in which the effects of one blood pressure QTL are isolated from all other blood pressure QTL in order that such strains can be used to define the physiological function of the QTL;(c) provide the basis for positional cloning and identification of blood pressure QTL, thus adding substantially to the fundamental understanding of the mechanisms of genetic hypertension.

我工作的总体目标是确定数量性状 控制大鼠血压的QTL。 一个范例， 这具有以下组成部分：（a）鉴定遗传标记， 在大鼠中与血压共分离;（B）在a. 大鼠染色体区域的分辨率为5-10厘摩（cM） 为了获得血压QTL的粗略定位， （c）为每个低血- 压力QTL等位基因的遗传背景上的近交Dahl盐- 高血压敏感（S）大鼠; d）在 含有QTL的染色体区域的分辨率为1- 2cM; 逐步替代法定位血压QTL 越来越小的染色体区域包含低血- 在S遗传背景上压制QTL等位基因; f）并最终制备 至少一个这样的QTL区域的物理图谱，并尝试定位 克隆。 目前的建议集中于制作密集的遗传图谱 以及大鼠血压QTL同源株的产生 染色体1、2和10，以及产生用于 这些染色体上血压QTL的精细遗传作图。 一级图谱的制备和血压QTL的定位 9号和13号染色体上也提出了。 对一个人的全基因组扫描 将对来自S和刘易斯大鼠的群体进行研究，以完成 这个特别翔实的十字架的描述，到目前为止， 得到4个血压QTL，占105 mmHg。 拟议的研究是重要的，因为它们将：（a）提供遗传学方面的信息， 可用于研究遗传性（原发性）高血压的标记物， 人;（B）提供同类菌株，其中一种血液的作用 血压QTL与所有其他血压QTL分离， 这些菌株可用于确定 QTL;（c）为定位克隆和鉴定提供基础 血压QTL，从而大大增加了基本的 了解遗传性高血压的机制。