Core D: Molecular Genomics Core

核心 D：分子基因组学核心

• 批准号: 7158295
• 负责人: FRANK R SHARP
• 金额: $ 5.61万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158295
• 关键词: animal tissue; autism; biomarker; biomedical facility; biotechnology; children; developmental genetics; developmental neurobiology; environmental health; functional /structural genomics; gene environment interaction; genetic markers; genetic susceptibility; halobiphenyl /halotriphenyl compound; human tissue; immunogenetics; metals; microarray technology; middle childhood (6-11); natural killer cells; neurotoxicology; pregnancy circulation; preschool child (1-5)

Core 4 is the Molecular Core. It serves as the central resource for the projects that isolate and process RNA on Affymetrix microarrays, and for performing RT-PCR confirmation of the microarray data for those projects. The UCD Affymetrix Core Facility is run by Dr. Jeffrey Gregg and is equipped with fluidics stations, hybridization ovens, and the new scanner required to scan the human Affymetrix U133 2.0PLUS arrays. Preliminary data from the previous CHARGE study has shown that there are changes in gene expression in the blood of children with autism compared to control children in the general population (GP) and to control children with mental retardation and developmental delay (MR/DD). The blood genomic profile in children with autism without regression (A) was different from controls, autism spectrum disorder (ASD) and different from children with autism with regression (A-R). In addition, there is a group of regulated genes in most children with A, A-R and with ASD that are expressed by natural killer (NK) cells in peripheral blood, suggesting an abnormality in this cell type that is common to all types of autism. These NK-cell related genes are expressed by all of the autism phenotypes including A, A-R and ASD, and hence may point to common pathways that underlie the common language and behavioral abnormalities in all three disorders. This core will be utilized by the projects as follows. Project #1: Aim #1: Perform genomic (RNA expression on microarrays) studies on blood from children with autism in the 4-9 year old range, and compare to the blood genomic profiles we have obtained in children with autism in the 2-5 year old age range. Aim #2. Compare gene expression as a function of blood metal levels in both age groups in A, A-R, ASD, MR/DD and GP groups. Aim #3. Examine genomic profiles in pregnant mothers who have previously given birth to an autistic child to determine if there is a specific genomic profile that correlates with whether the mother's fetus is destined to develop autism. Project #2. Aim #1. Describe the gene expression profiles in the blood using specific white blood cell subsets including NK cells for children with autism without regression, autism with regression, and ASD children compared to GP and delayed children. Aim #2. Examine gene expression following stimulation or activation of specific white blood cell subsets of A, A-R, ASD, MR/DD and GP children with: low level mercury; immune cell stimulation/activation with vaccine antigens and cell-specific mitogens; and xenobiotics. Project #3. Compare gene expression profiles in the blood of children with autism to the blood of experimental animals exposed to toxicants including organic mercury, PCB 95, and PBDE 47 (Project #3).

核心4是分子芯。它是隔离和处理项目的中心资源 Affymetrix微阵列上的RNA，并用于对其中的微阵列数据进行RT-PCR确认 项目。 UCD Affymetrix核心设施由Jeffrey Gregg博士运营，并配备了流体 扫描人Affymetrix U133 2.0plus所需的电台，杂交烤箱和新的扫描仪 数组。先前的电荷研究的初步数据表明，基因有变化 与对照儿童（GP）相比，自闭症儿童的血液表达（GP） 并控制患有智力低下和发育延迟的儿童（MR/DD）。血液基因组 自闭症儿童没有消退的儿童（a）的特征与对照，自闭症谱系障碍不同 （ASD），与患有自闭症的儿童有回归（A-R）不同。此外，还有一组 大多数具有A，A-R和ASD的儿童的调节基因由天然杀手（NK）细胞表达 在外周血中，表明这种细胞类型的异常是所有类型的自闭症。这些 NK细胞相关的基因均由所有自闭症表型表达，包括A，A-R和ASD，因此表达 可能指出的是普通语言和行为异常的共同途径 三个疾病。该核心将由如下项目使用。项目＃1：目标＃1：执行基因组 （在微阵列上的RNA表达）对4-9岁范围内自闭症儿童的血液的研究，以及 与我们在2-5岁的自闭症儿童中获得的血液基因组特征相比 范围。目标＃2。将基因表达与A，A-R中的两个年龄组中的血金属水平的函数进行比较 ASD，MR/DD和GP组。目标＃3。检查患有怀孕母亲的基因组特征 先前生育着自闭症儿童，以确定是否存在特定的基因组谱与 母亲的胎儿是否注定要发展自闭症。项目＃2。目标＃1。描述基因 使用特定的白色血细胞子集中的血液表达谱，包括儿童的NK细胞 自闭症没有回归，自闭症，回归和ASD儿童与GP相比并延迟 孩子们。目标＃2。检查特异性白细胞刺激或激活后的基因表达 A，A-R，ASD，MR/DD和GP儿童的子集：低水平的汞；免疫细胞 用疫苗抗原和细胞特异性有丝分子刺激/激活；和异种生物。项目＃3。 比较自闭症儿童血液中的基因表达谱与实验动物的血液 暴露于有机汞，PCB 95和PBDE 47（项目＃3）中。