《生命科学》 2014, 26(6): 571-582

孤独症的遗传病因学研究进展及基因型-表型关联研究计划

郭　辉^1，2，胡正茂^1，2，夏　昆^1，2*

(1 中南大学医学遗传学国家重点实验室，长沙 410078；2 中南大学生命科学学院，长沙 410013)

摘　要：孤独症谱系障碍是一组严重影响儿童健康，具有高度临床和病因异质性的神经发育障碍性疾病，其典型的临床症状包括社会交往障碍，语言交流障碍以及刻板、重复的行为。近年来依靠基因组学研究的发展，孤独症的遗传学研究取得了巨大进展。主要体现在利用基因组学方法对大样本量的孤独症散发患者和家系进行全基因组关联研究、拷贝数变异研究以及外显子组或全基因组测序研究，鉴定了一大批孤独症的易感或致病基因以及位点。虽然取得了瞩目的进展，但这些研究的结果也提出了极具挑战性的问题，即高度的遗传异质性。将对孤独症已有的遗传学研究进展做一综述，并基于已有的研究进展提出几种孤独症的病因学模型。同时，为了解决遗传异质性的问题，提出了孤独症基因型- 表型关联研究计划。这一计划将是孤独症下一步临床遗传学研究的重点方向。

Progress of the genetic etiology of autism spectrum disorders and the proposed genotype and phenotype correlation project    

GUO Hui^1，2， HU Zheng-Mao^1，2， XIA Kun^1，2*

(1 State Key Laboratory of Medical Genetics， Central South University， Changsha 410078， China; 2 School of Life Sciences， Central South University， Changsha 410013， China)

Abstract: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with impairments in reciprocal social interaction and communication， and the presence of restricted and repetitive behaviors. Epidemiology study has demonstrated that ASD has a high heritability. In the last decades， the genetic study of ASD has progressed strikingly， and more than hundreds of genes or loci have been identified by large cohort studies， such as genome wide association study， copy number variation study， whole exome or genome sequencing study. Although the progress is striking and the achievement is fruitful， a very challenging issue was emphasized: the extremely high genetic heterogeneity. In this paper， the recent progress of autism genetic study systematically are reviewed， and several genetic etiology models based on the existed progress are suggested. Lastly and most importantly， a project called “Genotype and Phenotype Correlation for Autism (GPCA)” aiming to resolve the genetic heterogeneity problem is proposed. This proposal will be the direction of ASD genetic study in the near future.