Identification of Obesity-Related QTLs

肥胖相关 QTL 的鉴定

• 批准号: 7470230
• 负责人: Anthony G. Comuzzie
• 金额: $ 56.54万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470230
• 关键词: Area; Bioinformatics; Body fat; Candidate Disease Gene; Cardiovascular Diseases; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 20; Chromosomes, Human, Pair 4; Complex; DNA Resequencing; Data; Data Set; Disease; Family; Family member; Gallbladder; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Polymorphism; Genome; Genotype; Heart; Individual; Localized; Maps; Measures; Mexican Americans; Mutation; Nucleotides; Nutritional; Obesity; Phenotype; Population; Principal Investigator; Quantitative Trait Loci; Risk Factors; Sampling; Short Tandem Repeat; Signal Transduction; Transcript; Variant; Work; base; cardiovascular disorder risk; design; follow-up; genetic linkage analysis; genome-wide linkage; insight; interest; novel; programs; resistin; trait; waist circumference

The major objective of Project 3 is to localize and identify the genes underlying previously detected QTLs for obesity-related phenotypes in the San Antonio Family Heart Study (SAFHS) which contribute to variation in risk of cardiovascular disease (CVD). This work is based upon large extended Mexican American families ascertained without regard to disease status. This sample represents -1400 family members which have been genotyped for >400 short tandem repeat markers in an 8 centimorgan map and for which genome-wide linkage analysis has been performed for a variety of phenotypes associated with obesity and which are recognized risk factors for CVD. In this project we will make use of recent advancements in high-throughput SNP typing and sequencing to saturate our areas of interest to further refine the region and help select positional candidate genes based on association implemented in a novel Bayesian quantitative trait nucleotide (BQTN) analysis designed to make use of complex family data sets. The identification and selection of these positional candidate genes will be further refined based on the application of an objective bioinformatics search routine along with insights provided by evidence of strong cis regulation of genes in the specific regions of interest identified from our unique whole genome transcript data for this population. Once strong positional candidate genes have been identified within our regions of interest, they will be resequenced within the set of founders for this sample to identify all common polymorphisms. Characterization of these polymorphisms will permit the remaining individuals to be genotyped and BQTN analysis will again be employed to identify the presence of potential functional variants in these positional candidate genes. When significant evidence of potential functional variants has been detected these polymorphisms will be typed in two additional family samples of Mexican Americans in order to look for replication.

项目3的主要目的是定位和识别先前检测到的QTL的基因 圣安东尼奥家庭心脏研究（SAFHS）中与肥胖相关的表型有助于变化 心血管疾病（CVD）的风险。这项工作基于大型墨西哥裔美国家庭 确定不考虑疾病状况。该样本代表-1400个家庭成员 在8厘米地图中以> 400个短串联重复标记进行了基因分型 已经针对与肥胖相关的多种表型进行了连锁分析 公认的CVD风险因素。在这个项目中，我们将利用高通量的最新进步 SNP打字和测序以使我们感兴趣的领域饱和，以进一步完善该区域并帮助选择 基于新型贝叶斯定量性状中实现的关联的位置候选基因 旨在利用复杂家庭数据集的核苷酸（BQTN）分析。标识和 这些位置候选基因的选择将根据目标的应用进一步完善 生物信息学搜索常规以及通过强烈的CIS调节基因中基因的证据提供的见解 从我们独特的整个基因组转录本数据中确定的特定利益区域。一次 在我们感兴趣的地区已经确定了强大的位置候选基因，它们将是 在该样品的创始人集中重新置换，以识别所有常见的多态性。 这些多态性的表征将允许其余个体进行基因分型和BQTN 分析将再次用于确定这些位置中潜在功能变体的存在 候选基因。当检测到潜在功能变异的大量证据时 多态性将在墨西哥裔美国人的另外两个家庭样本中输入，以便寻找 复制。