QTL mapping of cell number in the mouse CNS

小鼠中枢神经系统细胞数量的 QTL 定位

• 批准号: 7751917
• 负责人: GLENN D ROSEN
• 金额: $ 36.82万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751917
• 关键词: Address; Age; Anatomy; Area; Autistic Disorder; Bioinformatics; Bipolar Disorder; Brain; Breeding; Candidate Disease Gene; Cell Count; Celloidin; Cells; Cerebral cortex; Cognitive; Collection; Complement; Corpus striatum structure; Data; Databases; Development; Developmental reading disorder; Disease; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Variation; Genotype; Gilles de la Tourette syndrome; Haplotypes; Inbred Strains Mice; Individual; Investigation; Knowledge; Maps; Measures; Methods; Microarray Analysis; Molecular Profiling; Motor; Mouse Strains; Movement; Mus; Names; Neocortex; Neuroglia; Neurons; Parents; Phenotype; Play; Population; Process; Prosencephalon; Quantitative Trait Loci; RNA; Recombinants; Relative (related person); Research Personnel; Resources; Role; Schizophrenia; Specific qualifier value; Staging; Structure; System; Techniques; Telencephalon; Transcript; Variant; Work; cognitive function; design; developmental disease; executive function; genome-wide; neocortical; neurogenesis; programs; research study; segregation; trait

DESCRIPTION (provided by applicant): The cerebral cortex plays an essential role in the integration of higher cognitive functions, while the striatum is intimately involved in the coordination of movement and executive function. A variety of developmental disorders have been associated with perturbations of these anatomic regions, including developmental dyslexia, autism, schizophrenia, Tourette's syndrome, and bipolar disorders to name but a few. This proposal seeks to map quantitative trait loci (QTL) that modulate absolute and relative magnitudes of glial and neuronal cell numbers and regional volume in both the neocortex and striatum of the mouse. Using a genetic reference population , classic QTL mapping techniques, bioinformatic haplotype mapping, and microarray analysis of gene expression profiles, a small but important set of genes that are responsible for some of the remarkable quantitative differences seen among inbred strains of mice will be mapped. The following questions will be addressed: (1) What is the phenotypic variation in the volume and number of neurons and glia in the neocortex and striatum? (2) Are these quantitative differences due to the segregation of QTLs that selectively modulate the genesis of neurons and glial cells? (3) Is variation in cell number and volume of different regions of the telencephalon controlled by separate QTLs-specifically are striatal volume and neuron number modulated by QTLs independent of those for cerebral cortex? To answer these questions, highly accurate, unbiased, and efficient estimates of cell number and volume will be assessed by stereology. These traits will be mapped using GeneNetwork, a public online resource for the investigation of systems genetics. The QTL intervals thus defined will be narrowed using haplotype maps derived from sequence databases of the two parent strains, and by the creation of a database of gene expression levels of the BXD recombinant inbred set at different stages of development. All data gathered from these experiments will be added to GeneNetwork and will be publicly accessible. The questions addressed in the proposal have important implications for a number of disease states, including a variety of developmental disorders. The extension of current transcriptome databases to encompass gene expression analysis at various stages of development will enable a systems genetic approach to understanding fundamental aspects of brain development.

描述（由申请人提供）：大脑皮层在更高的认知功能的整合中起着至关重要的作用，而纹理与运动和执行功能的协调密切相关。各种发育障碍与这些解剖区域的扰动有关，包括发育阅读障碍，自闭症，精神分裂症，Tourette's综合征和双相情感障碍，仅举几例。该建议旨在绘制定量性状基因座（QTL），以调节小鼠的新皮层和纹状体中神经胶质和神经元细胞数的绝对和相对大小以及区域体积。使用遗传参考人群，经典的QTL映射技术，生物信息学的单倍型映射和基因表达谱的微阵列分析，这是一组小但重要的基因集，这些基因构成了一些小鼠中近交菌株中某些显着定量差异的造成显着定量差异。将解决以下问题：（1）新皮层和纹状体中神经元和神经胶质的体积和数量的表型变化是什么？ （2）由于QTL的分离，这些定量差异是否有选择地调节神经元和神经胶质细胞的起源？ （3）特定于单独的QTLS控制的端脑的不同区域的细胞数和体积的变化是纹状体体积和由QTL调制的纹状体体积和神经元数独立于大脑皮层的QTL？为了回答这些问题，将通过立体学评估对细胞数和体积的高度准确，无偏见和有效的估计。这些特征将使用GenEnetwork绘制，这是一种用于调查系统遗传学的公共在线资源。这样定义的QTL间隔将使用从两个母体菌株的序列数据库中得出的单倍型图来缩小范围，并通过创建BXD重组的基因表达水平的数据库，该数据库在不同发育的不同阶段设置。从这些实验中收集的所有数据都将添加到GenEnetwork中，并将公开访问。提案中解决的问题对许多疾病状态（包括各种发育障碍）具有重要意义。当前的转录组数据库的扩展以涵盖开发的各个阶段的基因表达分析，将使系统遗传方法能够理解大脑发育的基本方面。