肥胖表型全基因组印记连锁扫描和候选基因关联研究动物学专业论文.docxVIP

直接研究。既然LRP5基因在与肥胖相关的代谢途径和疾病起重要作 直接研究。既然LRP5基因在与肥胖相关的代谢途径和疾病起重要作 用，本论文假设并检验LRP5与肥胖以及相关性状显著关联。本研究 挑选了41个在LRP5基因内和基因附近的sNP(single nuc leotide polymorphism)进行基因分型，在有1873个个体的405个白人核心 家庭中，成功分型了27个SNP，它们的平均相问距离约为5kb，覆盖 了整个LRP5基因区域。本文运用家庭关联分析(即传递不平衡检测)， 研究了LRP5基因的多态性之间的连锁不平衡结构并构建单体型块进 行单体型关联分析。本研究发现LRP5基因的多态性不仅与肥胖显著 关联而且在研究的三个数量性状中得到一致的结果。本文鉴定了LRP5 基因的SNP标记以及它们的单体型与人类肥胖症以及肥胖相关表型 显著关联，可见LRP5基因在人类肥胖学中的重要作用。由于这是首 次研究发现了显著结果，为以后从分子生物学功能水平研究LRP5基 因与肥胖的关系奠定了基础。 关键词：肥胖，连锁分析，基因印记，关联分析，SNP，LRP5 II AbstractObesity Abstract Obesity is a condition of excess body fat that causes or exacerbates seVeral major public health problems．Common obesity is a polygenic and complex disorder arising from the genetic and environmental factors， as well as me interactions between them．As mai or risk factors for obesity body mass index(BMI)，fat mass and percentage of fIat mass(PFM)2ure under strong genetic determination，will the heriterbiliy over 0．5．Most of t11e studies use them as the surrogate phenotypes of obesity．Extensive studies haVe been conducted to decipher the genetic basis of human obesity． These studies， mainly using me linkage and association approaches，have achieved limited success and inconsistent／inconclusive results haVe accumulated．PreVious studis reVealed that imprinting may play an important role in af!f、ecting the propensity to obesity．Nevertheless， few whole genome genetic linkage studies have investigated the imprinting ef!|’ects on obesity in humans．So one of the aims for this study is to performe genomewide linkage scans to seaurch for loci with or without imprinting e日’ects for obesity’in a large pedigree sample with more than 4000 indiViduals．W色found signi6cant imprinting linkage signal at 2q37 in the whole genome scan． IIl non—imprinted liI水age analyses， we detecte4 suggestiVe lilll(age for 2q37 (LOD=2．23)． Interestingly’ 2q37 also achieVed a significant maternal linkage (LOD=3．34)in imprinted linkage analyses．This LOD score su印asses our significant threshold obtained by c