基因表达数量性状基因座定位的方法研究阿尔茨海默病的“遗传度缺失”

项目名称： 基因表达数量性状基因座定位的方法研究阿尔茨海默病的“遗传度缺失”

项目编号： No.81200828

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 陈颖

作者单位： 南通大学

项目金额： 23万元

中文摘要： 研究发现AD遗传度高，说明遗传因素在AD发病中起着决定性作用。但已知的AD易感基因却只能解释一小部分的AD遗传度，说明大量AD易感基因并未发现，此即AD的"遗传度缺失"。为寻找未知的AD候选基因，从而揭示AD"缺失的遗传度"，我们研究小组选择了适合AD遗传学分析背景，且同时满足高分辨率遗传作图群体要求的BXD RI小鼠为研究对象，并已完成70个品系的BXD RI小鼠海马组织基因表达资料的收集和部分AD相关基因的eQTL初步分析。本课题拟对AD的原发性病理因子-Aβ沉积过程中的一系列基因进行基因表达数量性状基因座（eQTL）定位的研究，构建Aβ相关基因的基因表达调控网络，筛选出控制Aβ沉积的重要节点，并进一步分析这部分基因在AD患者和正常人群间的序列多态性，提供其作为AD候选基因的临床证据，从而弥补AD"缺失"的遗传度，并为临床诊断提供新的分子标记。

中文关键词： 阿尔茨海默病；β-淀粉样蛋白；基因表达数量性状基因座；谷胱甘肽S转移酶Omega -1；甾醇氧－酰基转移酶１

英文摘要： There is evidence from familial aggregation that AD has a high heritability. However, AD associated genes can only explain a small proportion of the genetic contribution of AD, leaving several genetic risk factors to be identified, suggesting that they may account for the 'missing' heritability of AD. BXD RI mice were proposed to be used in expression Qutitative Trait Loci (eQTL) analysis, due to the genetic background differences associated with AD between B6 and D2, and a high density genetic map for linkage analysis. Gene expression data from 70 BXD RI mice hippocampus has been collected for eQTL analysis. Aβ has been postulated to be a causal factor in the pathogenesis of AD. The presence of Aβ-containing amyloid plaques is necessary for the neuropathological diagnosis of AD, suggesting that these entities may be involved in the etiology of the disease. In this study, we will construct Aβ associated gene network by eQTL mapping and the whole genome correlation analysis to identify the important control node in the accumulation of Aβ Plaques. Furthermore, we will isolate the sequence differences of AD candidate genes between AD patients and age-matched controls to validate the new AD candidate genes and provide molecular targets for AD diagnosis.

英文关键词： Alzheimer’s disease；β-amyloid；Expression Quantitative trait loci；Gsto1；Soat1