Molecular and Genetic Epidemiology of Autism

描述：自闭症是一种神经发育障碍，其特征是互惠的社会互动和沟通障碍，以及存在限制和重复的兴趣或行为模式。随着监测的改进和诊断标准的扩大，最近的流行研究表明，在美国，自闭症影响着多达1 / 300的儿童。治疗很少，而且大多数对非常显著的发病率几乎没有影响。我们对自闭症的病因知之甚少，但它确实有很强的遗传成分。尽管有这种显著的遗传效应，但过去十年的研究已经清楚地表明，潜在的遗传是复杂的，可能有几个基因独立作用，也可能相互作用，显著提高自闭症的风险。随着这一认识，自闭症遗传学领域正处于一个关键时刻。为了向前迈进，我们必须采用新的和创造性的范式来成功地剖析这种疾病的遗传病因。在目前的资助期内，我们强调了创新和已建立的基因组方法，以开始梳理自闭症遗传学的复杂结构。在我们的更新中，我们将扩展和建立在以前的结果上，拥抱新的基因组技术与新的统计方法的结合将带来成功的范例。具体而言，我们建议1)扩大我们的确定方案，包括自闭症谱系障碍表型的全部范围，2)确定19号染色体自闭症基因，3)在大型多代自闭症家族中研究新定义的与12号染色体的联系，4)扩展我们对GABA受体亚基基因的研究，5)确定临床同质的患者和家庭亚群，并使用改进的数据集来精细绘制ASD染色体区域和候选基因分析；6)测试新的基因/基因相互作用的证据，以充分解释自闭症风险谱。这些努力将结合起来，以解决儿童疾病中的一个重要问题，即自闭症谱系障碍的遗传学。

DESCRIPTION: Autism is a neurodevelopmental disorder characterized by impairments in reciprocal social interaction and communication and the presence of restricted and repetitive patterns of interest or behavior. With the improved surveillance and a broadening of the diagnostic criteria, the most recent prevalence study suggests that autism affects as many as 1 in 300 children in the US. Treatments are few and most have little impact on the very significant morbidity. Little is known about the etiology of autism, but it does have a strong genetic component. Despite this significant genetic effect studies over the past decade have clearly shown that the underlying genetics is complex with the likelihood that several genes acting independently as well as interactively significantly raise the risk of autism. With this realization the field of autism genetics is at a critical juncture. To move forward we must embrace new and creative paradigms to successfully dissect the genetic etiology of this disease. During the current funding period we have emphasized both innovative and established genomic approaches to begin teasing apart the complex weave of autism genetics. In our renewal we will expand and build on previous results embracing the paradigm that the wedding of new genomic technology with novel statistical methodology will bring about success. Specifically we propose to 1) Broaden our ascertainment scheme to include the full range of the autism spectrum disorder phenotype, 2) Identify the chromosome 19 autism gene, 3) Investigate a newly defined linkage to chromosome 12 in large extended multigenerational autism families, 4) Extend our studies of the GABA receptor subunits genes, 5) Identify clinically homogeneous subsets of patients and families and use the refined dataset to fine map ASD chromosomal regions and in candidate gene analyses, 6) Test for evidence of new gene/gene interactions to fully explain the spectrum of autism risk. These efforts will be integrated to address an important problem in childhood disease, the genetics of autism spectrum disorders.