"The development of genetics and genomics for analysis of quantitative traits"

“用于数量性状分析的遗传学和基因组学的发展”

• 批准号: 7508956
• 负责人: JOHN W. TAYLOR
• 金额: $ 34.43万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7508956
• 关键词: Alleles; Applications Grants; Architecture; Biology; Chromosome Mapping; Communities; Complex; Cooperative Behavior; Data; Development; Disease; Gene Expression; Genes; Genetic; Genetic Transcription; Genomics; Genotype; Germination; Growth; Human; Individual; Maps; Measurement; Measures; Methods; Modeling; Molds; Molecular; Neurospora; Neurospora crassa; Organism; Other Genetics; Pharmaceutical Preparations; Phenotype; Phylogenetic Analysis; Population; Public Health; Quantitative Trait Loci; Reading; Reproduction; Reproduction spores; Research; Resolution; Resources; Score; Shapes; Study models; Variant; Work; asexual; fungus; interest; mRNA Expression; research study; tool; trait

DESCRIPTION (provided by applicant): The objective of this grant proposal is to develop and make available to the community tools to identify genes responsible for any phenotype that can be measured in the model filamentous fungus, Neurospora crassa. We propose to develop as a community resource two large mapping populations, which will enable the identification of quantitative trait loci (QTLs) controlling naturally varying complex phenotypes. One of our populations comprises 500 wild isolates from a single phylogenetic clade of N. crassa, to be used for association mapping, the method of choice for identification of loci of small effect. The other population is an advanced intercross between two divergent N. crassa strains, to allow linkage mapping of rare alleles at high genetic resolution. For each population, we will measure genotype and gene expression via massively parallel signature sequencing using the Solexa platform. These resources will enable any research lab to score the strains for a trait of interest and map the underlying QTLs. As a proof of principle, we will characterize the wild and advanced intercross strains with respect to phenotypes that have broad interest to the Neurospora research community: asexual spore reproduction, sexual reproduction, vegetative growth, hyphal architecture and cooperative behavior during spore germination. We will pioneer the use of the mRNA expression data from our Solexa experiment to identify the molecular players underlying these macroscopic traits, as the expression of genes is shown to co-vary with traits across individuals. In addition, the expression measurements will be used to detail the N. crassa regulatory network, as we analyze covariation between expression levels and genetically map their controlling regulators. Our specific aims are (i) to construct the advanced intercross and characterize phenotypes that vary among these strains and the wild isolates; (ii) to perform short-read sequencing on cDNAs using the Solexa platform from each individual in each mapping population, to generate dense genotyping data and measure gene expression; and (iii) to conduct linkage and association mapping of mRNA expression and our proof-of-principle organismal traits. We believe that the mapping between genotypes, phenotypes, and gene expression levels that we propose would propel N. crassa to the forefront as a model for the study of natural variation in all eukaryotic species. Relevance to Public Health: Using N. crassa, we propose to study genetic differences between individuals that control traits like growth, organism shape, and sensitivity to drugs. N. crassa is a model for pathogenic fungi, and we aim to understand many aspects of its biology that are important for disease and treatment. Also, since so little is known about the 'principles of -genetic differences between individuals, our work will provide hypotheses about the genetics of other species, like humans.

描述（由申请人提供）：本拨款提案的目的是开发并向社区提供工具，以鉴定负责任何表型的基因，这些表型可以在模型丝状真菌粗糙脉孢菌中测量。我们建议开发作为一个社区资源的两个大的作图群体，这将使数量性状基因座（QTL）控制自然变化的复杂表型的鉴定。我们的一个种群包括500个来自N. crassa，用于关联作图，选择的方法用于鉴定影响小的基因座。另一个群体是两个不同的N. crassa菌株，以允许在高遗传分辨率下对稀有等位基因进行连锁作图。对于每个人群，我们将使用Solexa平台通过大规模并行签名测序测量基因型和基因表达。这些资源将使任何研究实验室能够对感兴趣的性状的菌株进行评分，并绘制潜在的QTL。作为一个原则的证明，我们将描述野生和先进的互交菌株的表型，有广泛的利益链孢菌研究界：无性孢子繁殖，有性生殖，营养生长，菌丝结构和孢子萌发过程中的合作行为。我们将率先使用来自Solexa实验的mRNA表达数据来识别这些宏观性状背后的分子参与者，因为基因的表达显示出与个体间的性状共变。此外，表达测量将用于详细说明N。crassa调控网络，因为我们分析了表达水平之间的协变，并从遗传学上绘制了它们的控制调控因子。我们的具体目标是（i）构建高级互交并表征这些菌株和野生分离株之间不同的表型;（ii）使用Solexa平台对每个作图群体中每个个体的cDNA进行短读段测序，以生成密集的基因分型数据并测量基因表达;以及（iii）对mRNA表达和我们的原理验证生物性状进行连锁和关联作图。我们相信，我们提出的基因型、表型和基因表达水平之间的映射将推动N。crassa作为研究所有真核生物物种自然变异的模型。 与公共卫生的相关性：使用N。crassa，我们建议研究控制生长，生物体形状和药物敏感性等性状的个体之间的遗传差异。N. crassa是致病真菌的模型，我们的目标是了解其生物学的许多方面，这些方面对疾病和治疗很重要。此外，由于对个体间遗传差异的原理知之甚少，我们的工作将提供有关其他物种（如人类）遗传学的假设。