GENOTYPE AND PHENOTYPE IN AUTISM AND RELATED BEHAVIORS

自闭症及相关行为的基因型和表型

• 批准号: 6570877
• 负责人: PATRICIA M RODIER
• 金额: $ 16.54万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570877
• 关键词: Asperger syndrome; autism; behavior test; biomarker; child (0-11); clinical research; cognition; congenital brain disorder; congenital nervous system disorder; developmental genetics; developmental neurobiology; disease /disorder etiology; emotions; eye movement disorders; gene mutation; genetic markers; genotype; human genetic material tag; human subject; language; language disorders; phenotype; polymerase chain reaction; southern blotting

Identification of the embryonic stage when injury can cause autism has led to the insight that the disorder is initiated by changes in the developing brain stem. The shortening of the hindbrain and loss of cranial nerve neurons in an animal mode of the insult and a human cause of autism resemble features of the Hox-1 transgenic knockout mouse. Thus, it is now possible to suggest a unifying hypothesis regarding the multiple etiologies of autism. We propose that teratogens and genetic defects lead to similar developmental changes in the brain stem because mutations of early developmental genes are the cause of familial cases and the teratogens which cause the disease act by interfering with function of the same genes. The new finding that one of the candidate genes is abnormal in some cases autism supports this hypothesis. This project will continue our attempt to identify genetic causes of autism based on data about the developmental origin and neuroanatomical phenotype responsible for some causes of the disease. We shall examine early developmental genes for mutation in cases of autism, Asperger's syndrome, Moebius syndrome, developmental language disorder with semantic-pragmatic features, and normal controls. It is our hypothesis that these syndromes are related to autism not only behaviorally, but etiologically, as well. Minor physical anomalies and neurological symptoms which have fixed the time of injury in some cases of autism will be investigated in all groups to determine whether there is evidence for the same time of origin in the related disorders. Behaviors affected in autism, including language, emotion, and cognition, will be described in each patient, and the data from biological markers and behavioral descriptions will be used to searched for clusters of cases related in phenotype or etiology. By evaluating the characteristics of all these groups with the same measures, we hope to define relationships that expand or refine the definition of autism. The goal of these studies is to produce biological markers for human causes of autism and provide genetic constructs for animal models of genetically- induced autism. The models will be created in Project I and tested behaviorally in Project II.

识别伤害可能导致自闭症的胚胎阶段已经导致 认识到这种疾病是由发育中的变化引起的 脑干。后脑缩短和脑神经丧失 动物模式中的神经元受到的侮辱和人类自闭症的原因 类似于 Hox-1 转基因敲除小鼠的特征。因此，现在是 可以提出关于多重性的统一假设 自闭症的病因学。我们认为致畸剂和遗传缺陷导致 由于突变导致脑干发生类似的发育变化 早期发育基因是家族性病例的原因， 导致疾病的致畸剂通过干扰细胞功能起作用 相同的基因。新发现其中一个候选基因异常 一些自闭症病例支持了这一假设。这个项目将继续我们的 尝试根据有关数据确定自闭症的遗传原因 发育起源和神经解剖表型负责一些 疾病的原因。我们将检查早期发育基因 自闭症、阿斯伯格综合症、莫比斯综合症、 具有语义语用特征的发展性语言障碍，以及 正常控制。我们的假设是这些综合症与 自闭症不仅在行为上，而且在病因上。轻微体力 异常和神经系统症状已确定受伤时间 将对所有群体中的一些自闭症病例进行调查，以确定 是否有证据表明相关的起源时间相同 失调。自闭症影响的行为，包括语言、情感和 认知，将在每个患者中进行描述，并且来自生物的数据 标记和行为描述将用于搜索集群 与表型或病因学相关的病例。通过评估 通过相同的措施，我们希望能够针对所有这些群体的特征 定义扩大或完善自闭症定义的关系。这 这些研究的目标是为人类原因产生生物标记 自闭症并为遗传性动物模型提供遗传构建体 诱发自闭症。模型将在项目 I 中创建并进行测试 项目 II 中的行为。