Genetic architecture of host response to tickborne disease in Peromyscus leucopus
白鼠蜱传疾病宿主反应的遗传结构
基本信息
- 批准号:10684792
- 负责人:
- 金额:$ 63.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-17 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAdultAnimalsAntibodiesBacteriaBiologicalBiological ModelsBloodBorrelia burgdorferiBreedingCRISPR gene driveCRISPR/Cas technologyCandidate Disease GeneChiropteraChromatinChromosome MappingChromosomesCommunitiesCompetenceCoupledDataDeer MouseDevelopmentDiploidyDiseaseDisease NotificationEbola virusEnhancersEquilibriumEuthanasiaFemaleGene TargetingGenesGeneticGenetic CrossesGenetic ModelsGenetic StructuresGenomeGenomic SegmentGenomicsGenotypeGoalsGrowthHaplotypesHigh PrevalenceHumanImmune responseImmunityInfectionInflammationInterventionKnock-outLarvaLife Cycle StagesLinkage DisequilibriumLyme DiseaseMammalsMeasurementMeasuresMediatingModelingMoltingMuridaeMusNorth AmericaNymphOrganParasitesPathologyPeromyscusPersonsPhenotypePopulationPrevalenceProcessResourcesRodentRodent ModelRoleSARS coronavirusSample SizeSkinTick-Borne DiseasesTicksTimeTissuesTransgenic ModelTransgenic OrganismsUnited StatesVariantVector-transmitted infectious diseaseWild Animalschronic infectioncohortcombatexperimental studyfootforward geneticsgenetic approachgenetic architecturegenome annotationgenome browsergenome wide association studygenome-wideinsightinter-individual variationinterestknockout genemalemicrobialpathogenprimary endpointpromoterrate of changesecondary endpointsegregationsuccesstick transmissiontick-bornetraittransmission blocking
项目摘要
Project Summary
Lyme disease, one of the most commonly reported infectious diseases in North America, is
caused by the tick-borne bacterium Borreliella burgdorferi. Although humans and other large
mammals can be infected by B. burgdorferi, in order to complete its life-cycle in the wild the
bacteria relies on rodent reservoirs, the major one being Peromyscus leucopus, the white-footed
deermouse. The role of P. leucopus in Lyme disease and several other tick-borne diseases is
analogous to that of bats as reservoirs for SARS coronaviruses and Ebola virus. In this proposal
we continue the development of P. leucopus as an emerging genetic model system for the study
of infectious and other diseases by maintaining and expanding genomic and biological
resources for this species. These resources are the starting point for any gene-focused
experiments in the Peromyscus genus. The primary goal of this proposal is to identify
segregating genetic factors that impact the competence of P. leucopus as a reservoir of B.
burgdorferi. The trait of reservoir competence is measured as the prevalence of infection and
corresponding bacterial burdens among a cohort of nymphs that had molted from larvae
previously fed on experimentally-infected deermice. Secondary endpoints include rates of
growth and decline of the bacteria in the blood and skin of the animals and selected host
responses, such as antibodies to the agent and inflammation of tissues, over the time course of
the infection. It would normally be extremely difficult to carry-out large-scale genotyping and/or
genetic crosses in an emerging rodent model. Here we show that our genome assembly for P.
leucopus in concert with low pass short read sequences from a long-term closed colony of
deermice can be leveraged to accurately impute SNP and haplotype genotypes on a genome-
wide scale. These genotypes are then used to identify genes contributing to the remarkable
capacity of P. leucopus to serve as a key reservoir host for B. burgdorferi and other disease
agents. Finally, a subset of identified genes will be validated via CRISPR/Cas9 gene knock-outs
in P. leucopus spearheaded by the person who pioneered transgenics for this genus. The
identification of reservoir competence mediating genes may suggest better interventions to
block transmission and provide insights into the management of human infections.
项目摘要
莱姆病是北美最常见的传染病之一,
由蜱传伯氏疏螺旋体引起虽然人类和其他大型
哺乳动物可被B感染。burgdorferi为了在野外完成它的生命周期,
细菌依赖于啮齿动物的水库,主要的一个是白足鼠,白足鼠
鹿鼠白足拟杆菌在莱姆病和其他几种蜱传疾病中的作用是
类似于蝙蝠作为SARS冠状病毒和埃博拉病毒的宿主。本提案中
我们继续发展P. leucopus作为研究的新兴遗传模型系统
传染病和其他疾病的基因组和生物
这个物种的资源。这些资源是任何以基因为重点的
实验在Peromyscus属。该提案的主要目标是确定
分离影响白柄侧耳作为B库的能力的遗传因素。
burgdorferi。储库能力的特征被测量为感染的患病率,
在一群从幼虫蜕皮的蝗虫中,
此前以实验感染的鹿鼠为食。次要终点包括
动物和选定宿主血液和皮肤中细菌的生长和衰退
反应,如抗体的代理和炎症的组织,随着时间的推移,
感染进行大规模的基因分型和/或
在一个新兴的啮齿动物模型中进行基因杂交。在这里,我们表明,我们的基因组组装P。
leucopus与来自长期封闭菌落的低通短读段序列一致
鹿鼠可以用来准确地估算基因组上的SNP和单倍型基因型-
大规模然后,这些基因型被用来识别有助于显著的
白足拟青霉是B的主要贮存宿主。Burgdorferi和其他疾病
剂.最后,将通过CRISPR/Cas9基因敲除来验证已鉴定基因的子集。
在P. leucopus中,由该属转基因技术的先驱者带头。的
储层能力介导基因的鉴定可能提示更好的干预措施,
阻断传播并为人类感染的管理提供见解。
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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Alan G. Barbour其他文献
Risk factors for staphylococcal toxic-shock syndrome.
葡萄球菌中毒性休克综合征的危险因素。
- DOI:
- 发表时间:
1981 - 期刊:
- 影响因子:5
- 作者:
M. W. Kehrberg;Robert H. Latham;Byron T. Haslam;Allen W. Hightower;Martha Tanner;Jay A. Jacobson;Alan G. Barbour;Vici Noble;Charles B. Smith - 通讯作者:
Charles B. Smith
Polymorphisms of major surface proteins of <em>Borrelia burgdorferi</em>
- DOI:
10.1016/s0176-6724(86)80107-9 - 发表时间:
1986-12-01 - 期刊:
- 影响因子:
- 作者:
Alan G. Barbour;Merry E. Schrumpf - 通讯作者:
Merry E. Schrumpf
New tricks of tick-borne pathogen
蜱传病原体的新技巧
- DOI:
10.1038/37475 - 发表时间:
1997-12-01 - 期刊:
- 影响因子:48.500
- 作者:
Alan G. Barbour;Wolfram R. Zückert - 通讯作者:
Wolfram R. Zückert
Alan G. Barbour的其他文献
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{{ truncateString('Alan G. Barbour', 18)}}的其他基金
Genetic architecture of host response to tickborne disease in Peromyscus leucopus
白鼠蜱传疾病宿主反应的遗传结构
- 批准号:
10469593 - 财政年份:2020
- 资助金额:
$ 63.8万 - 项目类别:
Genetic architecture of host response to tickborne disease in Peromyscus leucopus
白鼠蜱传疾病宿主反应的遗传结构
- 批准号:
10625699 - 财政年份:2020
- 资助金额:
$ 63.8万 - 项目类别:
Genetic architecture of host response to tickborne disease in Peromyscus leucopus
白鼠蜱传疾病宿主反应的遗传结构
- 批准号:
10265560 - 财政年份:2020
- 资助金额:
$ 63.8万 - 项目类别:
Pacific Southwest RCE for Biodefense & Emerging Infectious Diseases Research
太平洋西南生物防御 RCE
- 批准号:
7901228 - 财政年份:2009
- 资助金额:
$ 63.8万 - 项目类别:
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