"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）：本拨款提案的目标是开发并提供社区工具，以识别可在模型丝状真菌，粗神经孢子菌中测量的任何表型负责的基因。我们建议开发两个大型定位群体作为社区资源，这将使数量性状位点（qtl）的鉴定能够控制自然变化的复杂表型。我们的一个种群包括500个来自单一系统发育分支的野生分离株，用于关联作图，这是鉴定小效应位点的首选方法。另一个群体是两个不同的稻稻株之间的高级杂交，以便在高遗传分辨率下对罕见等位基因进行连锁定位。对于每个种群，我们将使用Solexa平台通过大规模并行特征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对感兴趣的性状进行评分，并绘制潜在的qtl。为了证明这一原理，我们将根据神经孢子菌研究界广泛关注的表型来描述野生和高级杂交菌株的特征：无性孢子繁殖、有性繁殖、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的分子参与者，因为基因的表达被证明与个体间的性状共同变化。此外，当我们分析表达水平之间的协变并绘制其控制调控因子的遗传图谱时，表达测量将用于详细描述草草调控网络。我们的具体目标是：(i)构建高级交叉并表征这些菌株和野生分离株之间的表型差异；（ii）使用Solexa平台对每个定位群体中每个个体的cdna进行短读测序，生成密集的基因分型数据并测量基因表达；以及（iii）进行mRNA表达的连锁和关联映射以及我们的原理证明的生物体特征。我们相信，我们提出的基因型、表型和基因表达水平之间的定位将推动N. crassa成为所有真核生物物种自然变异研究的前沿模型。

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

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

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