Center for Mouse Genomic Variation at Single Cell Resolution
Center for Mouse Genomic Variation at Single Cell Resolution
批准号:
10297730
负责人:
Seyed Ali Mortazavi
金额:
$128.48万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-08-24 至 2026-05-31
关键词:
ATAC-seqAdultAffectAlternative SplicingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAstrocytesBiologicalBiological AssayBiologyBlood CellsBrainBreathingCatalogsCell LineCell NucleusCellsChromatinCommunitiesComplexComputer ModelsDiseaseDisease modelEnsureFemaleFoundationsGene ExpressionGenesGeneticGenetic EngineeringGenetic VariationGenetic studyGenomeGenomic approachGenomicsHealthHeightHumanHuman GeneticsInbred MouseInbreedingIndividualInflammationJointsLibrariesLifeLinkMapsMeasuresMissionModelingMouse StrainsMusNational Human Genome Research InstituteNeuronsNucleotidesOrganOrganismOrganoidsPersonsPhenotypePre-Clinical ModelPredispositionProtein IsoformsProteinsProtocols documentationQuantitative Trait LociRNARNA SplicingRecombinantsRegulatory ElementResolutionResourcesRestRoleSamplingSignal TransductionSingle Nucleotide PolymorphismSourceSplit-Pool Ligation Transcriptome sequencingTREM2 geneTechniquesTissue SampleTissuesTranscriptUnited States National Institutes of HealthVariantWorkXCL1 genecell typecomputational pipelinesdesigndifferential expressionepigenomegene functiongenetic variantgenomic variationhuman diseasehuman modelhuman reference genomehuman tissueinsertion/deletion mutationinterestmacrophagemalemembermouse modelpre-clinicalprogramspromoterresponsesingle-cell RNA sequencingtooltranscriptometranscriptome sequencingtranscriptomics
中文摘要
每个人平均有500万个单核苷酸变异,
以可变拷贝数存在的插入、缺失和其他区域的核苷酸
与人类参考基因组相比。这些变量必须一起解释所有
遗传贡献的每一个表型的人,无论是他们的身高或他们的家族
易患复杂疾病。虽然我们可以快速测量这些
基因组中的变异,我们缺乏框架来了解哪些变异会影响
基因组功能或它们如何在活着的、呼吸的生物体中相互作用。核心
IGVF联盟的使命是利用基因组学方法,
单细胞技术和计算机建模。应用单细胞基因组学方法
选择不同的小鼠品系可以为使命做出强大的贡献,
财团的资源。我们的单细胞分辨率小鼠基因组变异中心
将首先使用38个小鼠协作杂交重组近交系,
对人类的序列多样性,以确定影响基因表达水平的变异,
8种不同组织中单核水平的染色质可及性。我们将测序
同时使用短读取测序和长读取测序两者的单核的子集
测序以鉴定影响不同转录物同种型表达的变体,
不同品系小鼠的不同细胞。我们还将测量
这些组织中的巨噬细胞响应LPS时这些CC系中的变体
刺激.由此产生的细胞类型表达QTL,染色质
易接近性QTL、剪接QTL和响应QTL图谱将有助于IGVF建模
组;用于表征重要的变体;并供更广泛的社区研究
这些组织的功能以及设计更好的人类疾病的临床前模型。
英文摘要
Any human being has on average 5 million single-nucleotide variants and 13 million
nucleotides of insertions, deletions, and other regions present in variable copy numbers
compared to the human reference genome. Together these variants must account for all of the
genetic contributions to every phenotype of that person, whether it is their height or their familial
predisposition to complex diseases. While we can quickly measure the presence of these
variants in a genome, we lack the framework to understand which of the variants impact
genomic function or how they interact with each other in living, breathing organisms. A core
mission of the IGVF Consortium is to identify variants that impact the expression of genes using
single-cell techniques and computational modeling. Applying a single-cell genomics approach to
selected diverse mouse strains can make a powerful contribution to the mission and to
resources of the Consortium. Our Center for Mouse Genomic Variation at Single Cell Resolution
will first use 38 mouse Collaborative Cross recombinant inbred lines that possess similar levels
of sequence diversity to humans to identify variants that influence gene expression levels and
chromatin accessibility at the single-nucleus level in 8 distinct tissues. We will sequence
simultaneously a subset of single-nuclei with both short-read sequencing and long-read
sequencing to identify variants that impact the expression of different transcript isoforms in
different cells across the different mouse strains. We will also measure the relationship of
variants in these CC Lines in the response of macrophages in these tissues in response to LPS
stimulation. The resulting resource catalogs of cell-type expression QTL, chromatin
accessibility QTL, splicing QTL, and response QTL maps will be useful for IGVF modeling
groups; for characterizing important variants; and for use by the wider community studying the
function of these tissues as well as for designing better pre-clinical models of human diseases.
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Center for Mouse Genomic Variation at Single Cell Resolution
-
批准号:10643874
-
项目类别:
-
资助金额:$253.43万
-
财政年份:2021
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Center for Mouse Genomic Variation at Single Cell Resolution
-
批准号:10474393
-
项目类别:
-
资助金额:$253.43万
-
财政年份:2021
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Defining the Mechanistic Link between C5aR1 signaling and cognitive loss in Alzheimer's diseases
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批准号:10213622
-
项目类别:
-
资助金额:$66.23万
-
财政年份:2018
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负责人:Seyed Ali Mortazavi
-
依托单位:
Higher Precision Human and Mouse Transcriptomes
-
批准号:10241205
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项目类别:
-
资助金额:$288.87万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Genetic and epigenetic mechanisms of FSHD pathogenesis
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批准号:10540086
-
项目类别:
-
资助金额:$42.75万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Genetic and epigenetic mechamisms of FSHD pathogenesis
-
批准号:10188423
-
项目类别:
-
资助金额:$43.31万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Functional Genomics and Bioinformatics Data management Core
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批准号:10708162
-
项目类别:
-
资助金额:$229.33万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Genetic and epigenetic mechamisms of FSHD pathogenesis
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批准号:9768158
-
项目类别:
-
资助金额:$44.65万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Functional Genomics and Bioinformatics Data management Core
-
批准号:10592221
-
项目类别:
-
资助金额:$228.3万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Higher Precision Human and Mouse Transcriptomes
-
批准号:9982475
-
项目类别:
-
资助金额:$56.79万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Genetic and epigenetic mechamisms of FSHD pathogenesis
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批准号:9264261
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项目类别:
-
资助金额:$45.53万
-
财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Single-nucleus profiling of FSHD heterogeneity
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批准号:9323738
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项目类别:
-
资助金额:$20.39万
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财政年份:2017
-
负责人:Seyed Ali Mortazavi
-
依托单位:
Comparative analysis of the 4D encoding of regulatory networks in stem cells
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批准号:8572810
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项目类别:
-
资助金额:$231.6万
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财政年份:2013
-
负责人:Seyed Ali Mortazavi
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依托单位:
海外基金