肥胖表型全基因组印记连锁扫描和候选基因关联研究

发布时间：2018-01-07 22:26

本文关键词：肥胖表型全基因组印记连锁扫描和候选基因关联研究　出处：《湖南师范大学》2006年硕士论文　论文类型：学位论文

【摘要】：肥胖症是一种体内脂肪堆积过多而严重影响人类健康的疾病。常见的肥胖是一种多基因疾病或复杂疾病,既受遗传的决定也受环境的影响,并且环境和遗传因素之间以及基因之间都可能存在相互作用。体重指数、脂肪含量和脂肪百分比是肥胖的重要风险因子,并有很强的遗传决定,遗传率一般都高于0.5。大量的研究以这些性状作为肥胖的替代表型。目前关于肥胖症的致病基因的寻找已经有大量的研究,主要包括全基因组扫描和候选基因的关联研究。但是结果大都存在不一致性。有研究表明印记基因或者基因组对肥胖的致病机理有影响,有关肥胖的全基因组扫描中很少考虑基因印记的作用,因此本文的一个目的是:在多于4000人的大型家系样本中进行全基因组扫描,并考虑基因印记的影响,在全基因组水平上以寻找肥胖的易感基因组区域。全基因组扫描的结果表明,染色体2q37有显著的印记连锁信号。在普通的连锁扫描中得到的LOD值为2.23,当构建母系印记效应连锁扫描时,连锁信号增加到3.34,该LOD值超过了本研究通过大量计算机模拟而确定的连锁显著性阈值。本研究还提示2q31、16q22、3p14、3q24和19q13几个染色体区域可能对肥胖形成的遗传有贡献。本研究进一步证明了在连锁统计遗传研究中考虑基因组印记和表型定义方面的重要性。通过全基因组连锁扫描寻找易感基因组区域是肥胖遗传研究的重要的一方面,而直接研究候选基因与肥胖相关表型的关系也显得非常重要。LRP5(低密度脂蛋白受体相关蛋白—5)基因,属于细胞表面受体低密度脂蛋白受体家族成员之一,研究已经证明LRP5在WNT信号通路中起重要作用,可能控制骨骼和眼睛的形成,同时对糖代谢和胆固醇代谢有着重要而显著的作用。有研究发现LRP5基因的多态性与一些肥胖有关的复杂疾病或性状相关联。但是至今还没有对LRP5基因多态性与肥胖症之间关系的
[Abstract]:Obesity is an excessive accumulation of body fat and seriously affect human health. Common obesity is a polygenic disease or complex disease, both genetic decision is also affected by the environment, and between environmental and genetic factors and gene may interact with each other. The body mass index, fat content and fat percentage is an important risk factor for obesity, and have a strong genetic determination, genetic rate is generally higher than 0.5. a number of studies on these as the surrogate phenotypes of obesity. The causative gene for obesity have been studied, including the association of whole genome scan and candidate gene. But the results are not consistency. Studies have shown that imprinted genes or genomes on the pathogenic mechanism of obesity may influence the whole genome scan about obesity is rarely considered genetic imprinting The effect, so a purpose of this paper is: a genome-wide scan was performed in a large pedigree sample of more than 4000 persons, and considering the effects of gene imprinting, at genomic level to find susceptibility of obesity. Genomic regions of whole genome scan results showed that chromosome 2q37 significant imprinting linkage signal. In general the linkage scan LOD value in 2.23, when the construction of the chain effect of maternally imprinted scan, linkage signal increased to 3.34, the LOD value exceeds this research through a large number of computer simulations to determine the significant linkage threshold. This research also suggests that the genetic region on chromosome 2q31,16q22,3p14,3q24 and 19q13 may be involved in the development of obesity contribution. This study further proves that considering the importance of genomic imprinting and phenotype definition in the study. Through the statistical genetic linkage whole genome linkage scan to find susceptibility Genomic region is an important aspect of obesity research, while to directly study the relationship between candidate gene and obesity related phenotypes is also very important for.LRP5 (low density lipoprotein receptor related protein 5) gene, belonging to the cell surface receptor of low density lipoprotein receptor family members of one of the studies have shown that LRP5 plays an important role in WNT the signaling pathway, may regulate bone and eye development, at the same time have significant effect on glucose metabolism and cholesterol metabolism. Studies have found that LRP5 gene polymorphism is associated with obesity related complex diseases or traits. But there is no relationship between LRP5 gene polymorphism and obesity

【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R346

【引证文献】