Functional Analysis of GWAS loci associated with hearing loss.
与听力损失相关的 GWAS 位点的功能分析。
基本信息
- 批准号:10593682
- 负责人:
- 金额:$ 25.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-12-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AcousticsAdultAffectAgeAllelesAnimal ModelBehaviorBiological ModelsCDH23 geneCRISPR/Cas technologyCandidate Disease GeneComplexDataDevelopmentDiagnosisDimensionsDiseaseDisease modelDrug ScreeningDyesEmbryonic DevelopmentEnsureFertilizationGene SilencingGenerationsGenesGeneticGoalsHair CellsHealthHearingHearing AidsHumanIn Situ HybridizationInfectionInjuryInternationalInvestmentsKnock-outLabelLabyrinthLarvaLibrariesMapsMechanoreceptorsMediatingMessenger RNAMethodsMolecularMonitorMorphologyMutagenesisMutationNoiseOrthologous GeneParticipantPathogenesisPathologyPatient Self-ReportPatternPersonsPharmaceutical PreparationsPhenotypePopulationPresbycusisQuality of lifeRehabilitation therapyReporterReporter GenesResourcesRoleStartle ReactionSwimmingSystemTechnologyTestingTissuesTransgenic OrganismsVariantVisualizationZebrafishbehavioral phenotypingcandidate identificationcausal variantcostdisease phenotypeexome sequencinggene functiongenome wide association studygenome-wide analysisgenomic locushearing impairmenthearing loss phenotypeinner ear developmentinsightknockout genelateral lineloss of functionmRNA Expressionmodel organismmutantneuromastneurosensorynext generation sequencingnovelnovel therapeuticsototoxicityparalogous genescreeningspatiotemporaltherapeutic development
项目摘要
Hearing loss is a highly prevalent and debilitating neurosensory disorder associated with substantially reduced
quality of life and overall health. It currently affects 430 million people worldwide; by 2050 this is expected to
increase to nearly 2.5 billion and result 1 in 10 people requiring rehabilitation. About 50% of cases are predicted
to have a genetic basis, however hearing loss can also be caused by other factors such as age, ototoxic drugs,
noise, infection or injury. Low-cost next generation sequencing technologies have facilitated many genome-wide
association studies (GWAS) and exome sequencing projects that have identified hundreds of variants and genes
associated with hearing loss. There are currently more than 150 loci and over 100 genes associated with non-
syndromic hearing loss, however few candidate genes have been identified for complex phenotypes such as
age-related hearing loss (ARHL) or
presbycusis, which
is becoming increasingly common as the population
ages. A GWAS conducted to identify candidate genes associated with ARHL identified 44 independent genomic
loci associated with hearing loss. A nearest gene was mapped for each SNP identified in this study, yet how this
SNP influences gene function in hearing loss has not been determined. Establishing a linkage between the target
genes and the disease phenotype is a huge challenge that ultimately affects the correct diagnosis; generating
similar phenotypes upon gene inactivation in animal models can establish a strong support for a candidate gene.
We identified 39 orthologs of 44 GWAS candidate genes in zebrafish, and further selected 29 novel genes that
will be tested functionally for their role in hearing loss by (1) generating a library of zebrafish mutants for 29 (and
paralogs) candidate genes associated with ARHL (2) analyzing these mutants via a high-throughput phenotyping
pipeline including morphological, cellular, and behavioral phenotypes. Identifying the functional consequences
of the candidate genes in zebrafish will yield mechanistic insights in disease pathogenesis.
听力损失是一种非常普遍和使人衰弱的神经感觉障碍,与大量减少有关
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Gaurav K Varshney其他文献
Gaurav K Varshney的其他文献
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{{ truncateString('Gaurav K Varshney', 18)}}的其他基金
Functional characterization of understudied protein kinases implicated in developmental disorders using zebrafish
使用斑马鱼研究与发育障碍有关的蛋白激酶的功能特征
- 批准号:
10217780 - 财政年份:2021
- 资助金额:
$ 25.58万 - 项目类别:
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