Insights into immune-related disease born from population genomics
对群体基因组学产生的免疫相关疾病的见解
基本信息
- 批准号:7992673
- 负责人:
- 金额:$ 55.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-06 至 2015-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAfricanAgeAllelesAllergic DiseaseAnimal ModelAntigensAsiaAutoimmune DiseasesAutoimmune ProcessBiologicalBlindnessCaucasiansCaucasoid RaceCellsCessation of lifeCharacteristicsChildChromosomesClinicalComplexDNADataDatabasesDeveloping CountriesDevelopmentDiagnosticDiseaseEnsureEquilibriumEvolutionFamilyGene DuplicationGene FamilyGenesGeneticGenetic PolymorphismGenetic RecombinationGenetic VariationGenomicsGraft RejectionHLA AntigensHaplotypesHealthHematopoietic Stem Cell TransplantationHumanHuman GenomeImmuneImmune responseImmune systemImmunogeneticsImmunoglobulin Variable RegionImmunoglobulinsImmunologyIndividualInfectionKiller CellsKnowledgeLeadLigandsLinkage DisequilibriumLymphocyteLymphocyte FunctionMalignant NeoplasmsMediatingMethodsMorbidity - disease rateMothersMusNK cell receptor NKB1Natural ImmunityNatural Killer CellsNatureOutcomePatientsPoint MutationPopulationPopulation GroupPredispositionPregnancyPrimatesPrincipal InvestigatorReceptor GeneReproductionResearchResistanceResolutionRunningSerologicalStagingSurveysSyndromeSystemT-Cell ReceptorT-LymphocyteTechniquesTherapeuticTimeTranslatingTransplantationTransplanted tissueVariantVasculitisWomancohortcostdesignflexibilitygenetic analysisgenetic associationhuman diseaseimmune functionimprovedinsightmortalitypatient populationpregnancy disorderpublic health relevancereceptorreproductive successtool
项目摘要
DESCRIPTION (provided by applicant): The 4.7Mbp HLA region contains numerous immune-system genes, notably those involved in detecting the presence of infection, malignancy and transplanted tissue and providing ligands that interact with lymphocyte receptors to trigger human innate and adaptive immune responses. Some of these genes are extraordinarily polymorphic, subject to balancing selection and associated with resistance/susceptibility to a wide range of infectious, autoimmune and allergic diseases, as well as being major arbiters of transplant rejection, graft-versus-
disease following hematopoietic stem cell transplantation, and pregnancy syndromes. Despite the wide-ranging importance of the HLA region, and its dominance in the genetic associations with many human
diseases, no concerted effort to systematically study the variation in HLA haplotype sequences has been undertaken. We propose to do this by developing a method that will allow characterization of hundreds of haplotypes in an accurate and cost-effective manner. Recent advances in immunology, have shown that killer-cell immunoglobulin-like receptors, which are primate-specific and reach their utmost complexity in the human species, are natural killer (NK) cell receptors for HLA class I, interactions that are formative in human innate immune defense and reproduction. That both HLA class I and KIR are highly polymorphic, but segregate on different chromosomes, is an extraordinary situation, because almost all individuals express receptors for ligands that they lack and vice versa. KIR polymorphism is increasingly being associated with disease, and in combination with HLA class I can yield stronger associations than either ligand or receptor alone. Because of these functional and genetic interactions, we will also sequence KIR haplotypes (130-250Kbp) from the same individuals whose HLA haplotypes are sequenced. The proposed research will cover the ethnic diversity of the human population, and will examine two types of disease that are associated with HLA/KIR factors. Central to this project is development of new methods that will advance biological understanding of
HLA and KIR diversity to much higher level, and will also be applicable to clinical HLA and KIR typing as diagnostics for disease and improving the choice of donors for therapeutic transplantation.
PUBLIC HEALTH RELEVANCE (provided by applicant): The human leukocyte antigen (HLA) complex and the killer cell immunoglobulin-like receptor (KIR) gene family are functionally interacting genomic regions associated with a wide range of human infectious and autoimmune diseases, as well as reproductive success and the outcome of therapeutic transplantation. In this project we will precisely define HLA and KIR genetic variation within the human population. This information will enable the identification of disease-causing genes and their mechanism of action.
描述(由申请人提供):4.7Mbp HLA区域包含许多免疫系统基因,特别是那些参与检测感染、恶性肿瘤和移植组织的存在,并提供与淋巴细胞受体相互作用以触发人类先天和适应性免疫反应的配体的基因。其中一些基因是非常多态的,受平衡选择的影响,与对广泛的感染性、自身免疫性和过敏性疾病的抗性/易感性相关,同时也是移植排斥反应、移植物抗-反应的主要仲裁者
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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PETER R PARHAM其他文献
PETER R PARHAM的其他文献
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{{ truncateString('PETER R PARHAM', 18)}}的其他基金
Functional genetics of human innate immunity in the bimodal gamma delta T cell response to Epstein-Barr Virus and in education of NK cells and their re-education to respond to autologous cells
人类先天免疫的功能遗传学在双峰 γδT 细胞对 Epstein-Barr 病毒的反应以及 NK 细胞的教育及其对自体细胞作出反应的再教育中
- 批准号:
10326842 - 财政年份:2019
- 资助金额:
$ 55.9万 - 项目类别:
Functional genetics of human innate immunity in the bimodal gamma delta T cell response to Epstein-Barr Virus and in education of NK cells and their re-education to respond to autologous cells
人类先天免疫的功能遗传学在双峰 γδT 细胞对 Epstein-Barr 病毒的反应以及 NK 细胞的教育及其对自体细胞作出反应的再教育中
- 批准号:
10552637 - 财政年份:2019
- 资助金额:
$ 55.9万 - 项目类别:
Insights into immune-related disease born from population genomics
对群体基因组学产生的免疫相关疾病的见解
- 批准号:
8105084 - 财政年份:2010
- 资助金额:
$ 55.9万 - 项目类别:
Insights into immune-related disease born from population genomics
对群体基因组学产生的免疫相关疾病的见解
- 批准号:
8292223 - 财政年份:2010
- 资助金额:
$ 55.9万 - 项目类别:
Insights into immune-related disease born from population genomics
对群体基因组学产生的免疫相关疾病的见解
- 批准号:
8486379 - 财政年份:2010
- 资助金额:
$ 55.9万 - 项目类别:
Insights into immune-related disease born from population genomics
对群体基因组学产生的免疫相关疾病的见解
- 批准号:
8676643 - 财政年份:2010
- 资助金额:
$ 55.9万 - 项目类别:
Insights into immune-related disease born from population genomics
对群体基因组学产生的免疫相关疾病的见解
- 批准号:
9307690 - 财政年份:2010
- 资助金额:
$ 55.9万 - 项目类别:
Insights into immune-related disease born from population genomics
对群体基因组学产生的免疫相关疾病的见解
- 批准号:
9100613 - 财政年份:2010
- 资助金额:
$ 55.9万 - 项目类别:
MHC CLASS I AND KIR GENE EVOLUTION IN HIGHER PRIMATES
高等灵长类动物 MHC I 类和 KIR 基因的进化
- 批准号:
7349828 - 财政年份:2006
- 资助金额:
$ 55.9万 - 项目类别:
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