QTL Mapping in Inbred FH Rat Strain for Alcohol Intake

近交 FH 大鼠品系中酒精摄入量的 QTL 定位

• 批准号: 6926600
• 负责人: Abbas Parsian
• 金额: $ 12.28万
• 依托单位: ARKANSAS CHILDREN'S HOSPITAL RES INST
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6926600
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; animal genetic material tag; animal tissue; behavioral /social science research tag; behavioral genetics; biological models; disease /disorder etiology; genetic polymorphism; genetic strain; genotype; inbreeding; laboratory rat; linkage mapping; preference; psychopathology; quantitative trait loci

DESCRIPTION (provided by applicant): The long-term goal of this revised project is to define the molecular bases for genetic contributions to the development of alcoholism. The immediate goal is to map and measure the contributions of individual gene loci, or QTL (quantitative trait loci), to the behavioral correlates of high ethanol intake and preference in Fawn-Hooded (FH)-derived rats. It has been well established that the standard linkage analysis using human family samples has little power to detect genetic linkage for psychiatric disorders. At the same time, detecting QTLs in animals and plants has become a routine practice. Therefore, we propose to map and measure the effects of individual genes, or QTL, influencing FH/Wjd rat behavioral traits in a cross between FH/Wjd rats with high ethanol intake and preference and a strain exhibiting low intake and preference (ACI/N). We have produced and phenotyped 612 F2s, 36 F1s, and 30 progenitor rats for alcohol intake and preference. Tissue samples (liver, spleen, brain, and kidney) have been preserved and stored from all of these animals. This sample is a valuable resource and has the potential to produce important results. Therefore, in this application, we are asking for funds to do genotyping and data analysis to explore (R21 mechanism) and identify new alcohol-related QTLs. This will be accomplished by collecting data on measuring molecular marker genotypes spaced throughout the rat genome in a F2 intercross population with extreme phenotypes formed by crossing an alcohol-preferring inbred rat strain (FH/Wjd) and an alcohol non-preferring inbred strain (ACI/N). Interval mapping will be used to map and measure the effects of QTLs in this intercross. Potential candidate genes within the intervals found to contain QTLs will be identified by comparative gene mapping and by scoring molecular polymorphisms for candidate genes in the intercross generation. Candidate gene polymorphisms will be included with the micro satellites in a fine scale mapping (by means of Advanced Intercross Lines) of potential QTL locations. The location of genes affecting alcohol related traits in rat genome will help to identify the systemic regions with similar effects in human genome. Finally, the identification of alcoholism-related genes will help to define their roles in the development of severe alcoholism.

描述（由申请人提供）：该修订项目的长期目标是定义分子碱基，以供饮酒的发展遗传贡献。直接目标是绘制和测量单个基因基因座或QTL（定量性状基因座）的贡献，对高乙醇摄入量的行为相关性和偏爱（FH）衍生的大鼠的行为相关性。已经很好地确定，使用人类家庭样本的标准链接分析几乎没有能力检测精神疾病的遗传联系。同时，在动物和植物中检测QTL已成为常规实践。因此，我们建议绘制和测量单个基因或QTL的效果，从而影响FH/WJD大鼠行为性状在FH/WJD大鼠之间具有高乙醇摄入量和偏好的交叉中，以及表现出低摄入量和偏好（ACI/N）的菌株。我们已经生产并表现为612 f2s，36 F1和30个祖先大鼠，用于酒精摄入和偏爱。组织样品（肝脏，脾脏，脑和肾脏）已被保存并存储在所有这些动物中。该样本是一种宝贵的资源，有可能产生重要的结果。因此，在此应用中，我们要求资金进行基因分型和数据分析以探索（R21机制）并识别与酒精相关的新QTL。这将通过收集有关在F2间交叉种群中测量分子标记基因型的数据来实现，该数据具有通过跨越酒精脱发的杂交大鼠菌株（FH/WJD）和酒精非偏爱的杂交菌株（ACI/N）形成的极端表型。间隔映射将用于映射和测量此互变的QTL的效果。在所发现的包含QTL的间隔内的潜在候选基因将通过比较基因映射和在间跨产生中为候选基因的分子多态性评分来鉴定。候选基因多态性将与潜在QTL位置的精细尺度映射（通过先进的跨线）中包括在微卫星中。影响大鼠基因组中与酒精相关性状的基因的位置将有助于鉴定在人基因组中具有相似作用的系统区域。最后，鉴定与酒精中毒相关的基因将有助于确定其在严重酒精中毒发展中的作用。