自闭症谱系障碍的分子遗传学研究进展

doi:10.16288/j.yczz.15-281

遗传 ›› 2015, Vol. 37 ›› Issue (9): 845-854.doi: 10.16288/j.yczz.15-281

• 综述 • 下一篇

自闭症谱系障碍的分子遗传学研究进展

赵晖¹, 张永超², 张永清¹

1. 中国科学院遗传与发育生物学研究所,分子发育生物学国家重点实验室,北京 100101;
2. 中国农业大学生物学院,北京 100193

收稿日期:2015-06-17 修回日期:2015-07-24 出版日期:2015-09-20 发布日期:2015-09-20
通讯作者: 张永清,博士,研究员,博士生导师,研究方向：发育神经生物学和重大神经疾病的动物模型。E-mail: yqzhang@genetics.ac.cn
作者简介:赵晖,博士研究生,专业方向：神经生物学。E-mail: zhaohui@genetics.ac.cn
基金资助:
科技部生殖与发育专项(编号：2014CB942803),国家自然科学基金委(编号：31110103907和31490590)和中国科学院脑先导项目(编号：XDB02020400)资助

Recent progresses in molecular genetics of autism spectrum disorders

Hui Zhao¹, Yongchao Zhang², Yongqing Zhang¹

1. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
2. College of Biological Sciences, China Agricultural University, Beijing 100193, China

Received:2015-06-17 Revised:2015-07-24 Online:2015-09-20 Published:2015-09-20

摘要/Abstract

摘要： 自闭症谱系障碍(Autism spectrum disorder, ASD)是一类常见神经发育疾病,以社会交往障碍、刻板重复行为与狭隘的兴趣为主要临床特征。在过去40年间,ASD患病率呈不断上升趋势,因而日益受到人们关注。近年来由于大规模外显子测序的应用,发现了许多新的ASD易感基因。这些易感基因富集在几个共同的遗传信号通路中,参与突触形成和染色质重构等。最新的动物模型研究表明,ASD的发病机制包括神经突触可塑性异常和神经回路兴奋性-抑制性平衡紊乱。本文从ASD遗传病因的高度异质性、众多致病基因突变影响的共同生物学过程以及遗传诊断方法和药物研发的进展等几个方面进行了综述,以期帮助人们深入了解ASD的遗传基础和转化研究现状。

关键词: 自闭症谱系障碍, 突触, 染色质重构, 微柱, 兴奋性-抑制性平衡

Abstract: Autism spectrum disorders (ASDs) are common neurodevelopmental disorders characterized by impaired social communication, restricted and repetitive behavior or interests. Over the past 40 years, the reported prevalence for ASDs has been steadily rising world-wide. Due to the application of large-scale exome sequencing in recent years, hundreds of novel ASD associated genes have been identified. These associated genes are enriched in several common genetic signaling pathways such as synapse formation and chromatin remodeling. Intensive studies in animal models have revealed abnormal synaptic plasticity and an imbalanced ratio of excitatory to inhibitory neurotransmission in neural circuits of ASD brains. In this review, we summarize recent advances in (1) genetic heterogeneity of ASDs, (2) molecular pathways disturbed by various genetic mutations in ASDs, and (3) the development of genetic diagnostics and pharmacological treatments for ASDs. This review aims to provide a brief overview of the genetic basis of ASDs and prospects for diagnosis and treatment for ASDs.

Key words: Autism spectrum disorders, synapse, chromatin remodeling, minicolumn, E/I balance

赵晖, 张永超, 张永清. 自闭症谱系障碍的分子遗传学研究进展[J]. 遗传, 2015, 37(9): 845-854.

Hui Zhao, Yongchao Zhang, Yongqing Zhang. Recent progresses in molecular genetics of autism spectrum disorders[J]. HEREDITAS(Beijing), 2015, 37(9): 845-854.

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自闭症谱系障碍的分子遗传学研究进展

Recent progresses in molecular genetics of autism spectrum disorders

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