Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
基本信息
- 批准号:9803109
- 负责人:
- 金额:$ 47.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAfricaAfrican AmericanAmericanAutoimmune DiseasesBacteriaBiological AssayBubonic PlagueCellsCentral AfricaChronicCollectionCommunicable DiseasesComplexDNADataDiseaseEnvironmentEuropeanEvolutionExposure toGene ExpressionGene FrequencyGenesGeneticGenetic DeterminismGenetic MarkersGenetic TranscriptionGenetic VariationGenetic studyGenotypeGrowthHost DefenseHourHumanHuman GenomeImmuneImmune responseImmune systemImmunityImmunologicsImmunologyIndividualInfectionInflammatoryMapsMeasuresMediatingModernizationMolecularNatural SelectionsNorthern AfricaPasteurella pseudotuberculosisPathogenicityPhenotypePlaguePlayPopulationPopulation GeneticsPopulation GroupPredispositionProxyQuantitative Trait LociRecording of previous eventsResistanceResolutionRoleSamplingShapesSingle Nucleotide PolymorphismTechniquesTechnologyTestingTimeVariantWorkYersiniaYersinia infectionsYersinia pestiscytokinefightingfunctional genomicsgenetic variantgenome-widegenome-wide analysishost-pathogen coevolutionhuman genomicsin vitro Assayinduced pluripotent stem cellinfancyinsightmacrophagenovelpandemic diseasepathogenpressureresponseskeletaltooltraittranscriptome sequencing
项目摘要
Project Summary
Pathogens are one of the strongest selective pressures on the human genome. As modern humans
migrated out of Africa, they encountered markedly different pathogenic environments, likely resulting in
population-specific selection of immune phenotypes. Consistent with this hypothesis, some of the most
compelling evidence for local positive selection in the human genome has been detected among genes
involved in immunity and host defense. Yet, our understanding of the role that local adaptation plays in
shaping phenotypic variation in immune responses across populations is still in its infancy. To better
understand the complex relationship between pathogens and host adaptation we propose to study the
selective impact on the immune system of one of the most devastating pathogens in history – Yersinia pestis,
the agent of the Black Death. Since its emergence in Eurasia 1500 to 6400 years ago Y. pestis has swept
Eurasia and North and Central Africa in two major pandemics (Justinian, 541-544; Black Death, starting 1347-
1351) and has subsequently spread nearly worldwide via a third ongoing pandemic. Although Y. pestis is
proposed to have severely culled the Eurasian population, how groups that differ in their historical exposure to
plague respond to the pathogen is not known. Addressing this gap is not only important for understanding the
recent evolution of the human immune system, but may also help reveal the molecular basis of ancestry-
related differences in susceptibility to infectious diseases, chronic inflammatory disorders, and autoimmune
disorders. Using combined expertise in human genomics, immunology, infectious diseases and ancient DNA,
we propose: (i) to characterize inter-individual and inter-population variability in immune responses to infection
with Y. pestis; (ii) to map expression quantitative trait loci (eQTLs) that are associated with variation in
response to infection with Y. pestis; and (iii) to identify genetic loci showing signatures of positive selection by
Y. pestis by looking at “real-time” fluctuations in allele frequencies among immune-related genes and
immunological QTLs sequenced from skeletal remains of European populations living before, during, and after
the Black Death. This work is expected to yield unprecedented insight into the genetic mechanisms associated
with increased protection against Y. pestis as well as reveal novel genetic markers involved in the susceptibility
to and/or protection against contemporary infectious diseases
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Luis Bruno Barreiro其他文献
Viral infections upregulate type-1 interferon and induce loss of oral tolerance in celiac disease
- DOI:
10.1016/j.dld.2014.07.027 - 发表时间:
2014-09-30 - 期刊:
- 影响因子:
- 作者:
Valentina Discepolo;Romain Bouziat;Jennifer Stencel;Mine Ikizler;Giuliana Lania;Merlin Nanayakkara;Alessandra Carrella;Marialaura Cuomo;Katia Ferrara;Renata Auricchio;Riccardo Troncone;Maria Vittoria Barone;Terence Dermody;Luis Bruno Barreiro;Bana Jabri - 通讯作者:
Bana Jabri
Luis Bruno Barreiro的其他文献
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{{ truncateString('Luis Bruno Barreiro', 18)}}的其他基金
Tissue destruction and healing in Celiac Disease
乳糜泻的组织破坏和愈合
- 批准号:
10518839 - 财政年份:2022
- 资助金额:
$ 47.67万 - 项目类别:
Tissue destruction and healing in Celiac Disease
乳糜泻的组织破坏和愈合
- 批准号:
10705152 - 财政年份:2022
- 资助金额:
$ 47.67万 - 项目类别:
Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
- 批准号:
10155522 - 财政年份:2019
- 资助金额:
$ 47.67万 - 项目类别:
Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
- 批准号:
10631544 - 财政年份:2019
- 资助金额:
$ 47.67万 - 项目类别:
Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
- 批准号:
10403998 - 财政年份:2019
- 资助金额:
$ 47.67万 - 项目类别:
Supplement: Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
补充:压力和基因组:测试社会效应对基因调控的影响
- 批准号:
9926548 - 财政年份:2017
- 资助金额:
$ 47.67万 - 项目类别:
Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
- 批准号:
10204868 - 财政年份:2017
- 资助金额:
$ 47.67万 - 项目类别:
Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
- 批准号:
9398561 - 财政年份:2017
- 资助金额:
$ 47.67万 - 项目类别:
Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
- 批准号:
8717684 - 财政年份:2012
- 资助金额:
$ 47.67万 - 项目类别:
Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
- 批准号:
8348248 - 财政年份:2012
- 资助金额:
$ 47.67万 - 项目类别:
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