Identification of Obesity-Related QTLs

项目3的主要目标是定位和识别与先前检测到的QTL相关的基因 圣安东尼奥家庭心脏研究(SAFHS)中与肥胖相关的表型导致 心血管疾病风险(CVD)。这部作品以墨西哥裔美国大家庭为基础 不考虑疾病状况而确定的。此示例表示-1400个家庭成员 在一个8厘米的图谱上对&gt；400短串联重复序列标记进行了基因分型，并对其进行了全基因组 已经对与肥胖相关的各种表型进行了连锁分析，这些表型 公认的心血管疾病危险因素。在这个项目中，我们将利用在高吞吐量方面的最新进展 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型贝叶斯数量性状中的实现 核苷酸(BQTN)分析旨在利用复杂的家族数据集。身份识别和 这些位置候选基因的选择将基于目标的应用而进一步细化 生物信息学搜索例程以及对基因的强大顺式调控的证据提供的见解 从我们独特的全基因组转录本数据中确定了这一群体的特定感兴趣区域。一次 在我们感兴趣的区域内已经发现了强烈的位置候选基因，它们将是 在这个样本的创始人集合中进行了重新测序，以确定所有常见的多态。 这些多态的特征将允许对其余的个体进行基因分型和BQTN 将再次使用分析来确定在这些位置的潜在功能变体的存在 候选基因。当检测到潜在功能变异的重要证据时，这些 将在另外两个墨西哥裔美国人的家庭样本中进行多态分析，以寻找 复制。

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.