Integrative Genomic Analyses of Human Evolution and Adaptation in Africa
Integrative Genomic Analyses of Human Evolution and Adaptation in Africa
批准号:
10357901
负责人:
Sarah Anne Tishkoff
金额:
$53.44万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-04-01 至 2025-01-31
关键词:
AfricaAfricanAfrican ancestryAnimal ModelBiologicalBiological AssayBiological ModelsBiomedical ResearchCRISPR/Cas technologyCell LineCellsCommunitiesComplexDataDietEvolutionGene ExpressionGeneticGenomic approachGenomicsHumanImmuneIn VitroKnowledgeLightLinkage DisequilibriumLuciferasesMetabolicModernizationNatural SelectionsPatternPersonsPhenotypePopulationRecording of previous eventsReporterSNP arraySamplingShapesSiteSourceStructureVariantbiomedical resourcecardiometabolismepigenomicsethnic diversityfield studyfunctional genomicsgenetic associationgenome sequencinggenome wide association studygenome-widegenomic variationgut microbiomein vivoin vivo Modelmetabolomemetabolomicsmicrobiomenovelphenotypic datatraittranscriptomicswhole genome
中文摘要
摘要
非洲是现代人的发源地,含有最高水平的人类基因组
变异,是过去现代人在世界范围内范围扩大的根源
10万年前。然而,关于非洲基因组和生物多样性的知识存在根本性的差距
表型变异,导致生物医学研究滞后,不仅在非洲人,而且在
新近的非洲人后裔。我们将应用一种综合进化基因组学方法
整合基因组、代谢组、微生物组、表观基因组和转录组数据
结合详细的表型数据重建非洲人口历史并更好地
了解非洲不同种族人群适应性特征的遗传基础。
具体地说,我们将使用全基因组SNP阵列以及高覆盖率的全基因组
对数据进行测序以确定这些群体中自然选择的目标并寻找基因
基因表达与人体测量、心脏代谢和免疫的关系
相关特征。我们将使用功能基因组学方法来确定因果调控基因座和
用高通量荧光素酶报告分析研究它们对体外基因表达的影响
在合适的细胞系中。我们还将使用Crispr-Cas9技术来验证和表征
人体细胞和体内模型系统中潜在的偶然变异的功能影响。
最后,我们将描述肠道微生物群的多样性,并检查与饮食、遗传因素的相关性。
和环境的变化。我们的数据将对非洲基因组有更深入的了解
多样性、种群结构和连锁不平衡模式对
全基因组关联研究在非洲裔中的成功应用和解释
人口。此外,这项研究将对理解遗传
中间表型(基因表达和代谢组)和复杂性状的基础
非洲人。此外,收集到的数据将成为生物医学研究的重要资源
社区。最后,我们的研究将揭示人类进化史和进化力。
塑造不同种族人类的基因组变异模式。
英文摘要
Abstract
Africa is the site of origin of modern humans, contains the greatest levels of human genomic
variation, and is the source of the worldwide range expansion of modern humans in the past
100,000 years. However, a fundamental gap in knowledge exists regarding African genomic and
phenotypic variation, resulting in a lag in biomedical research, not only in Africans, but also in
people of recent African descent. We will apply an integrative evolutionary genomics approach
incorporating genomic, metabolomic, microbiome, epigenomic, and transcriptomic data in
combination with detailed phenotypic data to reconstruct African population history and better
understand the genetic basis of adaptive traits in ethnically diverse African populations.
Specifically, we will use genome-wide SNP arrays as well as high-coverage whole genome
sequencing data to identify targets of natural selection in these populations and to look for genetic
associations with gene expression as well as anthropometric, cardio-metabolic, and immune
related traits. We will use functional genomics approaches to identify causal regulatory loci and
to study their impact on gene expression in vitro using high-throughput luciferase reporter assays
in appropriate cell lines. We will also use Crispr-Cas9 technology to validate and characterize the
functional impact of potential casual variants in both human cells and in vivo in model systems.
Lastly, we will characterize gut microbiome diversity and examine correlations with diet, genetic
and environmental variation. Our data will generate a deeper understanding of African genomic
diversity, population structure, and patterns of linkage disequilibrium that 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 intermediate phenotypes (gene expression and the metabolome) and of complex traits in
Africans. In addition, the data collected will be an important resource for the biomedical research
community. Lastly, our study will shed light on human evolutionary history and evolutionary forces
shaping patterns of genomic variation in ethnically diverse humans.
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会议论文
Integrative Genomic Analyses of Human Evolution and Adaptation in Africa
-
批准号:10561604
-
项目类别:
-
资助金额:$53.43万
-
财政年份:2020
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Integrative Genomics of Body Size and Metabolism in Ethnically Diverse Africans
-
批准号:9360249
-
项目类别:
-
资助金额:$28.94万
-
财政年份:2015
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Integrative Genomics of Body Size and Metabolism in Ethnically Diverse Africans
-
批准号:9014550
-
项目类别:
-
资助金额:$60.64万
-
财政年份:2015
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Integrative Genomics of Body Size and Metabolism in Ethnically Diverse Africans
-
批准号:9203636
-
项目类别:
-
资助金额:$59.45万
-
财政年份:2015
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Integrative nutrigenomic and metabolomic analyses of Africans with variable diets
-
批准号:8825139
-
项目类别:
-
资助金额:$36.97万
-
财政年份:2014
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Integrative nutrigenomic and metabolomic analyses of Africans with variable diets
-
批准号:9186547
-
项目类别:
-
资助金额:$35.61万
-
财政年份:2014
-
负责人:Sarah Anne Tishkoff
-
依托单位:
African Odyssey: An Integrative Genomics Analysis of Complex Physiologic Traits
-
批准号:8521309
-
项目类别:
-
资助金额:$77.22万
-
财政年份:2009
-
负责人:Sarah Anne Tishkoff
-
依托单位:
African Odyssey: An Integrative Genomics Analysis of Complex Physiologic Traits
-
批准号:8142824
-
项目类别:
-
资助金额:$79.2万
-
财政年份:2009
-
负责人:Sarah Anne Tishkoff
-
依托单位:
African Odyssey: An Integrative Genomics Analysis of Complex Physiologic Traits
-
批准号:7847397
-
项目类别:
-
资助金额:$79.58万
-
财政年份:2009
-
负责人:Sarah Anne Tishkoff
-
依托单位:
African Odyssey: An Integrative Genomics Analysis of Complex Physiologic Traits
-
批准号:7940796
-
项目类别:
-
资助金额:$80.0万
-
财政年份:2009
-
负责人:Sarah Anne Tishkoff
-
依托单位:
African Odyssey: An Integrative Genomics Analysis of Complex Physiologic Traits
-
批准号:8310042
-
项目类别:
-
资助金额:$79.2万
-
财政年份:2009
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Variation at Malaria Resistance Genes in Africans
-
批准号:7676585
-
项目类别:
-
资助金额:$29.05万
-
财政年份:2006
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Variation at Malaria Resistance Genes in Africans
-
批准号:7163530
-
项目类别:
-
资助金额:$27.8万
-
财政年份:2006
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Variation at Malaria Resistance Genes in Africans
-
批准号:7350208
-
项目类别:
-
资助金额:$0.51万
-
财政年份:2006
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Variation at Malaria Resistance Genes in Africans
-
批准号:7603082
-
项目类别:
-
资助金额:$29.62万
-
财政年份:2006
-
负责人:Sarah Anne Tishkoff
-
依托单位:
Variation at Malaria Resistance Genes in Africans
-
批准号:7024294
-
项目类别:
-
资助金额:$28.68万
-
财政年份:2006
-
负责人:Sarah Anne Tishkoff
-
依托单位:
海外基金