"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: 8109212
• 负责人: JOHN W. TAYLOR
• 金额: $ 35.18万
• 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 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8109212
• 关键词: Alleles; Applications Grants; Architecture; Biology; Chromosome Mapping; Communities; Complementary DNA; 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; 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）：该赠款建议的目的是开发并提供给社区工具，以识别负责在模型丝状真菌Neurospora Crassa中测量的任何表型的基因。我们建议作为社区资源发展两个大型映射种群，这将使能够识别控制自然变化的复杂表型的定量性状基因座（QTL）。我们的人群之一包括来自北乳杆菌的单个系统发育进化枝的500个野生分离株，用于缔合映射，这是鉴定小效应基因座的首选方法。另一个人群是两种不同的Crassa菌株之间的晚期间变，允许在高遗传分辨率下将稀有等位基因的连锁映射。对于每个人群，我们将通过使用Solexa平台进行大规模平行的签名测序来测量基因型和基因表达。这些资源将使任何研究实验室都能为感兴趣的特征评分菌株，并绘制基础QTL。作为原则的证明，我们将在神经孢子研究界广泛兴趣的表型中表征野生和先进的互变菌株：无性孢子繁殖，有性繁殖，营养生长，菌丝体系结构和孢子发芽期间的合作行为。我们将先驱从我们的Solexa实验中使用mRNA表达数据来识别这些宏观特征的分子参与者，因为基因的表达被证明与跨个体的特征显示出与特征共同变化。此外，当我们分析表达水平和遗传绘制其控制调节剂之间的协方差时，该表达测量将用于详细详细介绍Crassa调节网络。我们的具体目的是（i）构建先进的间断和表征这些菌株和野生分离株之间不同的表型； （ii）使用每个映射总体中每个人的solexa平台对CDNA进行简短的测序，以生成密集的基因分型数据并测量基因表达； （iii）进行mRNA表达和我们的原理特征的连锁和关联映射。我们认为，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Crassa的最前沿，以此作为研究所有真核物种自然变异的模型。 与公共卫生有关：使用N. Crassa，我们建议研究控制生长，生物体形状和对药物敏感性等特征的个体之间的遗传差异。 N. Crassa是致病真菌的模型，我们旨在了解其生物学的许多方面对疾病和治疗很重要。同样，由于对个人之间的遗传差异的原理知之甚少，因此我们的工作将提供有关其他物种（如人类）遗传学的假设。

项目成果

Massive changes in genome architecture accompany the transition to self-fertility in the filamentous fungus Neurospora tetrasperma.

• DOI: 10.1534/genetics.111.130690
• 发表时间: 2011-09
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Ellison CE;Stajich JE;Jacobson DJ;Natvig DO;Lapidus A;Foster B;Aerts A;Riley R;Lindquist EA;Grigoriev IV;Taylor JW
• 通讯作者: Taylor JW

Extracellular calcium triggers unique transcriptional programs and modulates staurosporine-induced cell death in Neurospora crassa.

• DOI: 10.15698/mic2014.09.165
• 发表时间: 2014-08-09
• 期刊: Microbial cell (Graz, Austria)
• 作者: Gonçalves AP;Monteiro J;Lucchi C;Kowbel DJ;Cordeiro JM;Correia-de-Sá P;Rigden DJ;Glass NL;Videira A
• 通讯作者: Videira A

Transcription profiling of the Neurospora crassa response to a group of synthetic (thio)xanthones and a natural acetophenone.

• DOI: 10.1016/j.gdata.2015.02.001
• 发表时间: 2015-06
• 期刊: Genomics data
• 作者: Pedro Gonçalves A;Silva N;Oliveira C;Kowbel DJ;Glass NL;Kijjoa A;Palmeira A;Sousa E;Pinto M;Videira A
• 通讯作者: Videira A

Nuclear and genome dynamics in multinucleate ascomycete fungi.

• DOI: 10.1016/j.cub.2011.06.042
• 发表时间: 2011-09-27
• 期刊: Current biology : CB
• 作者: Roper M;Ellison C;Taylor JW;Glass NL
• 通讯作者: Glass NL