Intergrative Genetics of Metabolic Syndrome Traits

代谢综合征特征的整合遗传学

基本信息

批准号：
8001061
负责人：
Aldons Jake Lusis
金额：
$ 42.44万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8001061
关键词：
Abbreviations Address Adipose tissue Algorithms Architecture Biopsy Blood Pressure Cardiovascular Diseases Chromosome Mapping Clinical Collaborations Complex Control Locus DNA Data Data Set Detection Diabetes Mellitus Diagnosis Diet Disease Distal Effectiveness Environmental Exposure Evaluation Fatty acid glycerol esters Finland Gene Expression Profile Genes Genetic Genomics Goals High Density Lipoprotein Cholesterol Human Inbred Strain Individual Instruction Lead Link Linkage Disequilibrium Lipoproteins Liver Maps Measures Metabolic syndrome Modeling Molecular Molecular Models Mus Nature Obesity Participant Pathway interactions Plasma Population Population Study Proteomics Public Domains Quantitative Trait Loci Recombinants Recording of previous events Regulatory Element Resolution Resources Structure Susceptibility Gene Tissues Transcript Validation Variant base clinical phenotype design dietary control disorder prevention experience gene environment interaction genetic analysis genetic linkage analysis glucose tolerance human data human subject interest lipid metabolism metabolomics molecular modeling molecular phenotype mouse model novel novel strategies positional cloning programs tool trait transcriptomics

项目摘要

PROJECT SUMMARY (See Instructions): During the present cycle of our PPG, we have developed a novel approach, which we term "integrative genetics", to help identify genes and pathways associated with the Metabolic Syndrome (MetSyn). We have also developed a new mapping tool in mice, which we term a "mouse diversity panel" (MDP), which allows high resolution mapping of traits such as gene-by-environment interactions. In the present proposal, we will apply these tools to two basic questions concerning the metabolic syndrome. The first question has to do with the nature ofthe molecular networks underlying human MetSyn traits. In our previous "integrative genetics" studies, we examined both molecular phenotypes (transcript levels) and clinical phenotypes in segregating mouse populations. This allowed us to identify genetic loci controlling transcript levels and model co-expression networks. We will now extend this approach to human populations. In collaboration with Dr. Markku Laakso, we will examine DNA variation and transcript levels in fat biopsies from 1,000 individuals in a MetSyn study population that has been typed for the major MetSyn traits. We will then identify genes and co-expression networks related to clinical traits. Gene-by-diet interactions are critically important in MetSyn, but they are notoriously difficult to study directly in human populations. We will use our mouse diversity panel to examine differences in biologic networks and clinical traits in mice maintained on either a chow diet or a high fat diet for 8 weeks. This will allow us to map genes controlled dietary responsiveness of MetSyn traits and to medol to co-expression networks perturbed by these genes. The mouse and human data will be integrated and aspects relevant to this program validated in collaborative studies with other Projects and the Cores.

项目摘要（参见说明）：在我们当前的 PPG 周期中，我们开发了一种新颖的方法，我们称之为“综合遗传学”，以帮助识别与代谢综合症（MetSyn）相关的基因和途径。我们还在小鼠中开发了一种新的作图工具，我们将其称为“小鼠多样性面板”（MDP），它可以对诸如在本提案中，我们将这些工具应用于有关代谢综合征的两个基本问题。第一个问题与人类 MetSyn 特征背后的分子网络的性质有关。在我们之前的“整合遗传学”研究中，我们检查了分离小鼠群体的分子表型（转录水平）和临床表型。这使我们能够识别控制转录水平的基因位点并建立共表达网络模型。我们现在将这种方法扩展到人类。我们将与 Markku Laakso 博士合作，检查 MetSyn 研究人群中 1,000 名个体的脂肪活检中的 DNA 变异和转录水平，这些人群已针对主要 MetSyn 特征进行了分型。然后我们将识别与临床特征相关的基因和共表达网络。基因与饮食的相互作用在 MetSyn 中至关重要，但众所周知，它们很难研究直接作用于人群。我们将使用我们的小鼠多样性面板来检查维持食物饮食或高脂肪饮食 8 周的小鼠的生物网络和临床特征的差异。这将使我们能够绘制控制 MetSyn 性状饮食反应的基因图谱，并分析受这些基因干扰的共表达网络。小鼠和人类数据将被整合，并且与该计划相关的方面将在与其他项目和核心的合作研究。