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.

识别胚胎阶段时受伤会导致自闭症的识别 关于这种疾病的见解是由发展的变化引发的 脑干。后脑的缩短和颅神经的丧失 神经元以侮辱和自闭症的人类原因处于动物模式 类似于HOX-1转基因敲除鼠标的功能。因此，现在是 可能提出关于多个倍数的统一假设 自闭症的病因。我们提出培育剂和遗传缺陷铅 大脑茎的类似发育变化，因为 早期发育基因是家族病例的原因， 引起疾病作用的畸胎组通过干扰功能 相同的基因。新发现，其中一个候选基因在 一些案例自闭症支持这一假设。这个项目将继续我们 试图根据有关的数据来识别自闭症的遗传原因 发育起源和神经解剖表型负责某些 疾病的原因。我们将检查早期发育基因的 自闭症，阿斯伯格综合征，莫比乌斯综合征的突变， 具有语义特征的发展语言障碍， 正常对照。我们的假设是这些综合征与 自闭症不仅在行为上，而且在病因上也是如此。次要物理 异常和神经系统症状，这些症状固定了受伤时间 某些自闭症病例将在所有小组中进行调查，以确定 是否有相关起源的证据 疾病。自闭症影响的行为，包括语言，情感和 认知将在每个患者中描述，生物学的数据 标记和行为描述将用于搜索群集 与表型或病因相关的病例。通过评估 所有这些群体的特征都采用相同的措施，我们希望 定义扩展或完善自闭症定义的关系。这 这些研究的目的是为人类原因产生生物标记 自闭症并为遗传模型提供遗传构建 诱发自闭症。这些模型将在项目I中创建并进行了测试 在项目II中行为上。