O'Roak Brian J, State Matthew W
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Autism Res. 2008 Feb;1(1):4-17. doi: 10.1002/aur.3.
Although genes have long been appreciated to play a critical role in determining the risk for pervasive developmental disorders, the specific transcripts contributing to autism spectrum disorders (ASD) have been quite difficult to characterize. However, recent findings are now providing the first insights into the molecular mechanisms underlying these syndromes and have begun to shed light on the allelic architecture of ASD. In this article, we address what is known about the relative contributions of various types of genetic variation to ASD, consider the obstacles facing gene discovery in this complex disorder, and evaluate the common methodologies employed to address these issues, including linkage, molecular and array-based cytogenetics, and association strategies. We review the current literature, highlighting recent findings implicating both rare mutations and common genetic polymorphisms in the etiology of autism. Finally, we describe key advances in genomic technologies that are transforming all areas of human genetics and consider both the opportunities and challenges for autism research posed by these rapid changes.
长期以来，人们一直认识到基因在决定广泛性发育障碍风险方面起着关键作用，但导致自闭症谱系障碍（ASD）的具体转录本却很难进行特征描述。然而，最近的研究结果首次揭示了这些综合征背后的分子机制，并开始阐明ASD的等位基因结构。在本文中，我们阐述了关于各类基因变异对ASD相对贡献的已知情况，探讨了在这种复杂疾病中进行基因发现所面临的障碍，并评估了用于解决这些问题的常用方法，包括连锁分析、分子和基于阵列的细胞遗传学以及关联策略。我们回顾了当前的文献，重点介绍了近期发现的罕见突变和常见基因多态性在自闭症病因学中的作用。最后，我们描述了正在改变人类遗传学各个领域的基因组技术的关键进展，并考虑了这些快速变化给自闭症研究带来的机遇和挑战。
