Discovery and Characterization of Quantitative Trait Nucleotides
数量性状核苷酸的发现和表征
基本信息
- 批准号:8507755
- 负责人:
- 金额:$ 28.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-30 至 2015-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAgricultureAllelesAnecdotesArchitectureBehavioralBiologyC. elegans genomeCaenorhabditis elegansCatalogingCatalogsCollectionComplexComplex Genetic TraitComplex MixturesDataDevelopmentDiseaseDissectionEnvironmentFrequenciesGene FrequencyGenesGeneticGenetic EpistasisGenetic PolymorphismGenetic RecombinationGenetic VariationGenomeGenomicsGenotypeGoalsHealthHeritabilityHumanInbreedingIndividualKnowledgeLearningLeftMapsMeasuresMethodsModelingMolecularMutationNematodaNucleotide MappingNucleotidesOrganismPhenotypePhysiologyPopulationPopulation DistributionsPopulation GeneticsPredispositionQuantitative Trait LociReadingRecombinantsReporterResearchResolutionResourcesShapesSorting - Cell MovementSpecificityStagingTissuesTranscriptTransgenic OrganismsVariantX Chromosomeabstractingbasedesigndisorder riskgenetic variantgenome wide association studygenome-widehuman diseasepleiotropismsuccesstherapy developmenttooltrait
项目摘要
(4.4.6) PROJECT SUMMARY/ABSTRACT
Heritable variation underlies variation in human health, and the molecular basis for that variation is
largely uncharacterized. Recent results suggest that heritable variation in human disease risk may be
shaped by a complex mixture of rare alleles, common alleles of small effect, and alleles of all
frequencies whose effects depend on allelic states at other loci. Such complexity is expected for
quantitative traits under stabilizing selection, such as human physiology, and the complex architecture
of such traits is a major obstacle to their genetic dissection. Knowledge of the genetic variants
underlying complex traits is central to methods for ameliorating or predicting disease risk and for
developing therapies for treatment. Transcript abundance traits in the nematode C. elegans are a
promising model for variation in complex traits under stabilizing selection. These traits are amenable
to full genetic dissection using panel of near-isogenic inbred lines of that vary within a small interval of
the X chromosome implicated in heritable variation in hundreds of transcript abundance traits.
Creation and study of such a permanent mapping resource will permit identification of the causal
variants underlying variation in transcript abundances at the resolution of individual sequence
variants, generating a catalog of quantitative trait nucleotides. Such a catalog will reveal the types of
mutations that contribute to variation in complex traits, their modes of action, their additive and
interactive effect sizes, their frequencies in natural populations, and the distribution of their effects
across tissues and developmental stages and environments. Quantitative trait nucleotides mapped to
single-variant resolution have never been collected for any multicellular organism, and their features
will inform efforts to discover the genetic basis of complex disease traits in humans.
(4.4.6)项目概要/摘要
遗传变异是人类健康变异的基础,这种变异的分子基础是
基本上没有特征。最近的研究结果表明,人类疾病风险的遗传变异可能是
由罕见的等位基因、影响小的常见等位基因和所有等位基因的复杂混合物形成。
其影响取决于其他基因座的等位基因状态的频率。预计这种复杂性将在
稳定选择下的数量性状,如人体生理学和复杂的结构,
这是对它们进行基因解剖的主要障碍。基因变异的知识
潜在的复杂性状是改善或预测疾病风险以及
开发治疗方法。线虫C.优雅是一种
稳定选择条件下复杂性状变异的理想模型。这些特征是可以接受的
使用一组近等基因近交系进行全面的遗传解剖,
X染色体与数百种转录本丰度性状的遗传变异有关。
建立和研究这种永久性的绘图资源将有助于确定
在单个序列分辨率下转录本丰度变异的基础变异
变异,生成数量性状核苷酸的目录。这样的目录将揭示
导致复杂性状变异的突变,它们的作用方式,它们的加性和
交互效应大小,它们在自然群体中的频率,以及它们的效应分布
跨越组织、发育阶段和环境。数量性状核苷酸映射到
单变量分辨率从来没有收集到任何多细胞生物,其特征
将有助于发现人类复杂疾病特征的遗传基础。
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cryptic genetic variation: evolution's hidden substrate.
- DOI:10.1038/nrg3688
- 发表时间:2014-04
- 期刊:
- 影响因子:0
- 作者:Paaby AB;Rockman MV
- 通讯作者:Rockman MV
Multigenic natural variation underlies Caenorhabditis elegans olfactory preference for the bacterial pathogen Serratia marcescens.
- DOI:10.1534/g3.113.008649
- 发表时间:2014-02-19
- 期刊:
- 影响因子:0
- 作者:Glater EE;Rockman MV;Bargmann CI
- 通讯作者:Bargmann CI
The QTN program and the alleles that matter for evolution: all that's gold does not glitter.
- DOI:10.1111/j.1558-5646.2011.01486.x
- 发表时间:2012-01
- 期刊:
- 影响因子:0
- 作者:Rockman MV
- 通讯作者:Rockman MV
Resistance to germline RNA interference in a Caenorhabditis elegans wild isolate exhibits complexity and nonadditivity.
- DOI:10.1534/g3.113.005785
- 发表时间:2013-06-21
- 期刊:
- 影响因子:0
- 作者:Pollard DA;Rockman MV
- 通讯作者:Rockman MV
Natural Variation in plep-1 Causes Male-Male Copulatory Behavior in C. elegans.
- DOI:10.1016/j.cub.2015.09.019
- 发表时间:2015-10-19
- 期刊:
- 影响因子:0
- 作者:Noble LM;Chang AS;McNelis D;Kramer M;Yen M;Nicodemus JP;Riccardi DD;Ammerman P;Phillips M;Islam T;Rockman MV
- 通讯作者:Rockman MV
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Matthew Rockman其他文献
Matthew Rockman的其他文献
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{{ truncateString('Matthew Rockman', 18)}}的其他基金
EDGE CMT: deleterious recessive variation - from experimental data to predictive models
EDGE CMT:有害的隐性变异 - 从实验数据到预测模型
- 批准号:
10675239 - 财政年份:2023
- 资助金额:
$ 28.87万 - 项目类别:
Mechanisms of radiation tolerance in Caenorhabditis from Chernobyl
切尔诺贝利秀丽隐杆线虫的辐射耐受机制
- 批准号:
10162588 - 财政年份:2020
- 资助金额:
$ 28.87万 - 项目类别:
Genetic analysis of segregating recessive variation
分离隐性变异的遗传分析
- 批准号:
9218968 - 财政年份:2017
- 资助金额:
$ 28.87万 - 项目类别:
Genetic analysis of segregating recessive variation
分离隐性变异的遗传分析
- 批准号:
9679797 - 财政年份:2017
- 资助金额:
$ 28.87万 - 项目类别:
Discovery and Characterization of Quantitative Trait Nucleotides
数量性状核苷酸的发现和表征
- 批准号:
8119653 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
Discovery and Characterization of Quantitative Trait Nucleotides
数量性状核苷酸的发现和表征
- 批准号:
8306930 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
Discovery and Characterization of Quantitative Trait Nucleotides
数量性状核苷酸的发现和表征
- 批准号:
7937997 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
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