MOLECULAR GENETICS OF AUTISM

自闭症是一种严重的发育障碍，每10,000人中有2-10人患有自闭症 个人。而双胞胎和家庭研究支持重要的基因 参与，具体的遗传方式尚不清楚 乘性基因作用、遗传异质性和可变表达 可能存在潜在的易感基因。在未知的情况下 自闭症复杂的遗传模式，成功定位 自闭症的潜在疾病基因需要对数百个 跨越基因组和大样本大小的遗传标记以获得 有足够的力量找到潜在的基因。此外，候选基因 基于功能或职位的研究是一种互补的策略 一种综合性的方法来理解遗传病的分子遗传学基础 自闭症。 这个项目的目标是通过以下方式定位自闭症的疾病基因 系统的基因组搜索和候选基因分析。在多站点中 国际合作努力，240个有受影响兄弟姐妹的家庭 将收集自闭症患者对，并对高度多态的患者进行基因分型 以规则的、紧密的间隔跨越人类基因组的标记。美国 合作小组将确定120个受影响的家庭并进行表型分析 患有自闭症的兄弟姐妹，并将家庭的血液送到英国 细胞系的转化。英国-欧洲合作者组织， 通过自己的资金来源，将额外筹集120套 亲属配对和基因分型工作将在独立的 实验室设施。通过这一国际努力 大约有240对基因可以被识别出来。此外，候选人 将使用传递/不平衡检验来研究基因 5-羟色胺。多巴胺能。GABA能及相关疾病候选 (结核性硬化症)。连锁不平衡研究，在350年进行 只有一个孩子的自闭症家庭和80个有一个孩子的自闭症家庭 阿斯伯格障碍将允许确定是否存在 参与单纯性自闭症、多发性自闭症的不同易感基因 自闭症，或阿斯伯格综合症。自闭症的易感基因曾经是 确定了它们在自闭症临床变异性中的作用 自闭症患者中可能存在较温和的变异体，包括社会性 功能性缺陷、情绪和焦虑症可以被识别出来。在……里面 此外，确定自闭症的遗传决定因素 开发改进的治疗干预措施的基础 针对自闭症的病理生理学。

Autism is a severe developmental disorder afflicting about 2-10 per 10,000 individuals. While twin and family studies support significant gene involvement, the specific mode of genetic inheritance is unknown and multiplicative gene action, genetic heterogeneity, and variable expression of underlying susceptibility genes are probable. Given the unknown and complex mode of genetic inheritance in autism, success in localizing underlying disease genes in autism will require evaluation of hundreds of genetic markers spanning the genome and large sample sizes to obtain sufficient power to find underlying genes. In addition, candidate gene studies based on function or position are complementary strategies in a comprehensive approach to understanding the molecular genetic basis of autism. The goals of this project are to localize disease genes in autism through a systematic genome search and candidate gene analysis. In a multi-site international collaborative effort, 240 families with affected sibling pairs with autism will be collected and genotyped on highly polymorphic markers spanning the human genome at regular, close intervals. The U.S. collaborative group will identify and phenotype 120 families with affected siblings with autism and send blood from the families to U.K. for transformation of cell lines. The U.K.-European group of collaborators, through their own funding resources, will collect an additional set of 120 relative pairs and genotyping efforts will be conducted in an independent laboratory facility. Through this international effort susceptibility genes can be identified in approximately 240 pairs. In addition candidate genes will be studied using the transmission/disequilibrium test for serotonergic. dopaminergic. GABAergic and associated disease candidates (tuberculous sclerosis). Linkage disequilibrium studies, conducted in 350 families with only one child with autism and 80 families with a child with Asperger's disorder will allow determination of whether there arc different susceptibility genes involved in simplex autism, multiplex autism, or Asperger's disorder. Once susceptibility genes for autism are identified, their role in the clinical variability in autism and in the expression of putative milder variants in autism, including social functioning deficits, mood, and anxiety disorders may be identified. In addition, identification of the genetic determinants in autism would lay the groundwork for development of improved treatment interventions targeting the pathophysiology of autism.