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的主要目标是定位和鉴定先前检测到的QTL的基因， 圣安东尼奥家族心脏研究（SAFHS）中与肥胖相关的表型， 心血管疾病（CVD）的风险。这项工作是基于大规模的墨西哥裔美国家庭 不考虑疾病状态而确定。这个样本代表了1400个家庭成员， 在8 centimorgan图谱中对>400个短串联重复标记进行基因分型， 已经对与肥胖相关的多种表型进行了连锁分析， 心血管疾病公认的危险因素。在这个项目中，我们将利用最新的进展，在高通量 SNP分型和测序使我们感兴趣的区域饱和，以进一步细化区域并帮助选择 基于关联的位置候选基因在一种新的贝叶斯数量性状中的应用 核苷酸（BQTN）分析，旨在利用复杂的家庭数据集。确定和 这些位置候选基因的选择将基于目标的应用而被进一步细化 生物信息学搜索例程沿着由在细胞中基因的强顺式调节的证据提供的见解， 从我们独特的全基因组转录本数据中鉴定出的特定感兴趣区域。一旦 在我们感兴趣的区域内已经确定了强位置候选基因，它们将被 在该样品的创始者组内重新测序，以鉴定所有常见的多态性。 这些多态性的特征将允许其余个体进行基因分型和BQTN检测。 将再次采用分析来鉴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体的显著证据时， 多态性将在另外两个墨西哥裔美国人的家庭样本中进行分型，以寻找 复制的