African Odyssey: An Integrative Genomics Analysis of Complex Physiologic Traits

非洲奥德赛：复杂生理特征的综合基因组学分析

基本信息

批准号：
8142824
负责人：
Sarah Anne Tishkoff
金额：
$ 79.2万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8142824
关键词：
Africa African Alleles Architecture Biological Biology Communicable Diseases Comparative Physiology Complex Complex Genetic Trait DNA DNA Sequence Rearrangement Data Development Diet Disease Disease susceptibility Dissection Environment Environmental Risk Factor Epigenetic Process Etiology European Eye Color Gene Expression Genes Genetic Genetic Transcription Genome Genomics Genotype Height Human Human Genetics Individual Internet Knowledge Life Life Style Maps Molecular Non-Insulin-Dependent Diabetes Mellitus Physiological Population Predisposition Recording of previous events Role Sample Size Skin Pigmentation Small RNA System Systems Biology Technology Time Translating Variant abstracting developmental genetics gene interaction genetic variant genome wide association study insight metabolomics novel success trait transcriptomics

项目摘要

DESCRIPTION Abstract One of the major challenges in the post-genomic era is understanding the complex web of genetic, developmental, physiological, and environmental interactions underlying continuous trait variation, including susceptibility to disease. Although there have been notable successes in mapping Mendelian traits, there have been relatively few successes in the dissection of the genetic architecture of complex traits involving multiple loci and environmental factors. We know even less about the genetics of complex trait variability in Africa, a region that had been under-represented in human genetics studies. Recent advances in the development of high-throughput genotyping, gene expression, and sequencing technologies now facilitate approaches that incorporate genotype and gene expression data from thousands of loci in thousands of individuals. A systems biology approach, which incorporates information about genetic interactions and transcription networks, and focuses on how naturally occurring genetic variants perturb these networks, may be more successful than traditional approaches for dissecting the genetic architecture of complex variable traits and for identifying functional variants. Equally important is understanding how these molecular networks are influenced by environmental factors including diet, lifestyle, and infectious disease status. For these reasons, I plan to use a novel integrative genomics approach, incorporating genomic, transcriptomic, and metabolomic data obtained from genetically, ethnically and geographically diverse Africans living in distinct environments. These data will provide, for the first time, a detailed knowledge of the comparative physiology of genetically and culturally diverse Africans and a detailed understanding of human evolutionary history in Africa. I will use a systems and evolutionary biology approach to identify genetic and environmental factors that influence complex physiologic traits, including disease susceptibility, in these populations.

描述抽象的后基因组时代的主要挑战之一是了解持续性状变异（包括疾病易感性）背后的遗传、发育、生理和环境相互作用的复杂网络。尽管在绘制孟德尔性状方面取得了显着的成功，但在剖析涉及多个基因座和环境因素的复杂性状的遗传结构方面却相对较少成功。我们对非洲复杂性状变异的遗传学知之甚少，该地区在人类遗传学研究中代表性不足。高通量基因分型、基因表达和测序技术的最新进展现在促进了整合来自数千个个体的数千个基因座的基因型和基因表达数据的方法。系统生物学方法结合了有关遗传相互作用和转录网络的信息，并专注于自然发生的遗传变异如何扰乱这些网络，可能比剖析复杂可变性状的遗传结构和识别功能变异的传统方法更成功。同样重要的是了解这些分子网络如何受到环境因素（包括饮食、生活方式和传染病状况）的影响。出于这些原因，我计划使用一种新颖的综合基因组学方法，整合从生活在不同环境中的遗传、种族和地理不同的非洲人获得的基因组、转录组和代谢组数据。这些数据将首次提供有关遗传和文化多样化的非洲人的比较生理学的详细知识，以及对非洲人类进化史的详细了解。我将使用系统和进化生物学方法来识别影响这些人群复杂生理特征（包括疾病易感性）的遗传和环境因素。