Genetic Components of Autism Spectrum Disorders

超过。空间 但前提是。 自闭症是一种严重的神经发育障碍，以沟通障碍、社交异常为特征 相互作用，僵化或重复的兴趣和行为。尽管有强有力的证据表明一个重要的 基因对自闭症病因的贡献，隔离导致自闭症的特定基因缺陷 真的很难。我们计划寻求两种互补的途径来寻找自闭症易感基因。 首先，我们将对收集和评估的150个核心家庭单元进行连锁分析 项目。通过患有自闭症的先证者、直系亲属和大家庭(如果有)确定的 成员的特点将是一系列检查语言能力领域的工具， 与社会相关，以及重复和僵化/强迫行为。这些领域中的每一个都展示了 这些领域的遗传性和先天障碍在非自闭症亲属中被发现的比率增加。 患有自闭症的先驱。我们最近对特定语言障碍(SLI)的遗传连锁研究表明 SLI和自闭症之间至少有一个易感基因是相同的。我们计划计算这些基因的遗传力 在我们的样本中测试电池中的项目，并选择最易遗传的用于连锁分析。我们将使用 一项分两个阶段的设计，完成对前75个家系的全9厘米密度基因组扫描，对 其余家系在产生暗示连锁结果的基因座上。整个样品将用于 任何高度暗示或显著的连锁结果的精细映射。寻找自闭症的第二个策略 易感基因将使用TRIO进行大规模关联分析(自闭症先证者和 两位家长)来自为这个项目收集的家庭，以及来自AGRE，NIMH的藏品 人类遗传学倡议样本和科里尔自闭症资源样本。我们预计大约 850个三人组将适合并可供使用。因为关联方法具有检测遗传效应的能力 我们将使用此样本来调查具有 在我们的工作和其他人的工作中，显示出与自闭症或语言表型的暗示联系。

EXCEED THE. SPACE PROVIDED. Autism is a serious neurodevelopmental disorder characterized by deficits in communication, abnormal social interactions, and rigid or repetitive interests and behaviors. Although there is strong evidence of an important genetic contribution to the cause of autism, the isolation of specific genetic defects that cause autism has been difficult. We plan to pursue two complementary avenues to search for autism susceptibility genes. First, we will conduct linkage analysis on a set of 150 nuclear family units collected and assessed for this project. Ascertained through a proband with autism, immediate and, when available, extended family members will be characterized by a battery of instruments that examine the domains of language ability, social relatedness, and repetitive and rigid/compulsive behavior. Each of these domains has demonstrated heritability, and impariments in these domains are found at increased rates among non-autistic relatives of probands with autism. Our recent genetic linkage study on specific language impairment (SLI) suggests that at least one susceptibility locus is shared between SLI and autism. We plan to calculate the heritability of the items in our test battery in our sample, and select the most heritable for use in linkage analysis. We will use a two-stage design, completing a full 9 cM density genome scan on the first 75 families, genotyping the remaining families at loci producing suggestive linkage results. The entire sample will be used for fine-mapping of any highly suggestive or significant linkage results. The second strategy to search for autism susceptibility genes will be to conduct large-scale association analyses using trios (proband with autism and two parents) from the families collected for this project, as well as the collections from AGRE, the NIMH Human Genetics Initiative samples and the Coriell Autism Resource samples. We anticipate approximately 850 trios will be suitable and available for use. As association methods have power to detect genetic effects that may be poorly detected by linkage, we will use this sample to investigate regions that have demonstrated suggestive linkage to autism or language phenotypes in our work and the work of others.