Utah Autism Program

描述（由申请人提供）：此续期申请提出三个项目和三个核心，以扩展与自闭症相关的表型研究。免疫成分将解决四个具体目标：1)研究血清素与免疫失调之间的相互作用；2)表征自闭症患者T细胞和抗体的特异性和自身反应性；遗传学组件将收集受影响病例及其亲属的DNA和临床信息（包括中间表型、更广泛的自闭症表型、头围、血清素水平和由免疫组件识别的免疫表型的储存血清）。评估将对犹他州人口数据库中已经确定的五个犹他州扩展谱系进行评估，并对两个新的扩展谱系进行评估，这些谱系将通过UPDB对800个新的自闭症病例进行新的搜索，这些病例是通过调查、州卫生部和犹他大学诊所确定的。使用Marshfield哺乳动物基因分型服务进行5厘米基因组扫描。将使用临床表型和中间表型分析系谱以绘制易感位点。在连锁峰下和/或被免疫组分鉴定的5个候选基因将使用snp进行基因分型。DNA、全血（用于未来的血清素）和血清（用于未来的免疫表型）将储存在800名新自闭症患者及其父母身上，用于未来基于家庭的关联研究。神经成像部分将研究自闭症患者，采用结构和功能成像研究来解决以下具体目标：1)描述结构脑容量的纵向变化及其与临床表型变化的关系；2)描述脑结构、白质结构和完整性、脑激活和脑化学之间的关系；3)研究大脑异常与免疫功能之间的关系（由免疫成分评估）。研究对象将与免疫组研究的对象重叠。

DESCRIPTION (provided by the applicant): This renewal application proposes three projects and three cores to extend studies of phenotypes associated with autism. The Immune Component will address four specific aims: 1) investigate the interaction between serotonin and immune dysregulation; 2) characterize the specificity and autoreactivity of T cells and antibodies in subjects with autism; The Genetics Component will collect DNA and clinical information on affected cases and relatives (including intermediate phenotypes, broader autism phenotype, head circumference, serotonin levels, and stored serum for immune phenotypes identified by the Immune Component). Assessments will be done on five extended Utah kindreds already identified through the Utah Population Data Base, and on two new extended pedigrees to be identified through a new UPDB search of 800 new autism cases identified through surveys and the State Health Department and University of Utah Clinics. A 5 cM genome scan will be done using the Marshfield Mammalian Genotyping Service. Pedigrees will be analyzed using the clinical phenotype and intermediate phenotypes to map susceptibility loci. Five candidate genes under linkage peaks and/or identified by the Immune Component will be genotyped using SNPs. DNA, whole blood (for future serotonin), and serum (for future immune phenotyping) will be stored on the 800 new autism cases and their parents for future family-based association studies. The Neuroimaging Component will study persons with autism, employing structural and functional imaging studies to address the following specific aims: 1) describe longitudinal changes in structural brain volumes and their relationships to changes in clinical phenotypes; 2) describe relationships among brain structure, white matter structure and integrity, brain activation, and brain chemistry; 3) study associations between abnormalities of the brain and immune function (as assessed by the Immune Component). Subjects will overlap with those studied by the Immune Component. COMPONENT PROJECTSPROJECT I Immunology (Robert Fujinami, Ph.D., pp. 96-130) DESCRIPTION [provided by applicant]: The Immunology Project proposes to investigate the role of serotonin in inducing dysregulation of the immune response. The investigator will examine the specificity and autoreactivity of T cells and antibodies present in children with autism. He will determine whether immune effector cells and antibodies induce or mimic CNS features often observed in autistic subjects such as hippocampal and mammillary body changes. Finally, he proposes to perform microarray analyses on RNA isolated from peripheral blood mononucler cells of autistic children versus control subjects.