权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Integrative Genomics of Body Size and Metabolism in Ethnically Diverse Africans

不同种族非洲人体型和代谢的综合基因组学

基本信息

批准号：
9360249
负责人：
Sarah Anne Tishkoff
金额：
$ 28.94万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-15 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9360249
关键词：
Address Affect Africa African African American Anatomy Biological Biological Assay Biomedical Research Body Size Cameroon Carbohydrates Cardiovascular Diseases Cell Line Communities Complex Custom DNA Data Diabetes Mellitus Disease Environment Etiology European Exhibits Fatty acid glycerol esters Gene Expression Genes Genetic Genetic Variation Genomic Segment Genomic approach Genomics Genotype Goals Growth Growth Factor Height Hormonal Hormones Human Immunity In Vitro Individual Insulin Knowledge Length Leukocytes Light Limb structure Linear Models Linear Regressions Linkage Disequilibrium Lipids Longevity Malignant Neoplasms Maps Metabolic Metabolic syndrome Metabolism Modernization Natural Selections Nucleic Acid Regulatory Sequences Pathway interactions Pattern Phenotype Plasma Play Population Recording of previous events Reporter Reproduction Research Role SNP array Sampling Seasons Shapes Signal Pathway Site Somatotropin Structure Testing Tissue-Specific Gene Expression Variant Weight Work admixture mapping base biomedical resource carbohydrate metabolism diabetes risk ethnic diversity farmer field study functional genomics genetic association genetic variant genome sequencing genome wide association study genome-wide genomic variation human genomics hypothalamic-pituitary-thyroid axis life history lipid metabolism lymphoblastoid cell line metabolic phenotype novel phenotypic data pituitary gland development pleiotropism public health relevance response trait whole genome

项目摘要

DESCRIPTION (provided by applicant): Elucidating the genotype-to-phenotype map is a primary goal of human genomics research. However, a fundamental gap in knowledge exists regarding African genomic and phenotypic variation, resulting in a lag in biomedical research in these populations. African populations harbor immense amounts of genetic diversity and exhibit substantial amounts of phenotypic variation, including body size, lipid and carbohydrate metabolism that are associated with risk for diabetes and cardiovascular disease, partly due to adaptation to diverse environments. Here, we propose to perform field studies to collect novel biological samples as well as detailed phenotypic data on anthropometric and metabolic traits from short statured Pygmy hunter-gatherers in Cameroon and neighboring tall-statured Bantu-speaking farmers. We will apply an integrative evolutionary genomics approach incorporating genomic, metabolic, and gene expression data to better understand the genetic basis of complex adaptive traits, including body size and metabolism, in these under-represented ethnically diverse Africans. Specifically, we will identify novel genetic variants using high coverage whole genome sequencing. We will also use genome-wide SNP arrays to identify targets of natural selection in these populations and to look for genetic associations with anthropometric, hormonal, and cardio-metabolic traits in Pygmy hunter-gatherers and Bantu farmers. We will use functional genomics approaches to identify new candidate loci and to study the impact of candidate variable sites on gene expression in vitro using high-throughput reporter assays in appropriate cell lines. These data will enable us to test the hypothesis that short stature in Pygmies may be a byproduct of selection for traits influenced by genes with pleiotropic effects on metabolism, reproduction, and immunity. The biological samples and data collected will be an important resource for the biomedical research community. In addition, our data will generate a deeper understanding of African genomic diversity, population structure, and patterns of linkage disequilibrium which are critical for the successful application and interpretation of genome wide association studies in African-descent populations. Furthermore, this study will have important implications for understanding the genetic basis of complex traits in Africans, etiology of short stature as well as other traits and diseases influenced by the GH/IGF1 pathway, such as metabolic syndrome, diabetes, cardiovascular disease, longevity, and cancer. Lastly, our study will shed light on human evolutionary history and evolutionary forces shaping patterns of genomic variation in ethnically diverse humans.