孤独症的遗传学和神经生物学研究进展

发布时间：2018-08-20 07:37

【摘要】：孤独症是一种遗传度高达90%的多基因复杂疾病,具有典型的遗传和表型异质性,并受到环境因素的影响.本文对近年来孤独症遗传学、表观遗传学和神经生物学3方面的进展进行了简要综述.细胞遗传学法、全基因组扫描及候选基因法是孤独症分子遗传学研究中较为常见的3种方法.虽然应用上述方法发现了一些孤独症易感基因集中的染色体区域,但确切的致病或易感基因仍未被检出.因而,越来越多的关注被集中于如何提高样本同质性、如何将遗传学机制与环境作用相联系、如何提高微效基因的检出率上.在提高样本同质性方面,功能核磁共振及交叉表型的研究正在进行.同时,表观遗传学的研究可以联系遗传与环境因素,从而更好地解释孤独症的发病机制.目前,对染色体上表观遗传与遗传共同调控的区域,如7号和15号染色体长臂,进行了大量研究.在神经生物学方面,神经递质、神经发育及神经免疫学假说均有一定的进展.其中,针对神经递质的研究主要集中于5-羟色胺、?-氨基丁酸及谷氨酸.在神经发育假说方面,神经发育相关蛋白,如肝细胞生长因子、神经生长因子及Reelin,研究得较为深入.
[Abstract]:Autism is a multi-gene complex disease with a heritability of up to 90%. It has typical genetic and phenotypic heterogeneity and is affected by environmental factors. The advances in autism genetics, epigenetics and neurobiology in recent years are reviewed in this paper. Cytogenetics, genome scanning and candidate gene method are three common methods in molecular genetics of autism. Although some chromosomal regions of autistic susceptibility genes have been identified by the above method, the exact pathogenicity or susceptibility genes have not been detected. Therefore, more and more attention has been focused on how to improve the homogeneity of samples, how to link genetic mechanisms with environmental effects, and how to improve the detection rate of micro-effect genes. Studies on functional nuclear magnetic resonance (fMRI) and cross-phenotypes are under way to improve homogeneity of samples. At the same time, epigenetics can be linked to genetic and environmental factors, so as to better explain the pathogenesis of autism. At present, a large number of studies have been carried out on the regions of epigenetic and genetic regulation on chromosomes, such as the long arms of chromosomes 7 and 15. In neurobiology, neurotransmitters, neurodevelopmental and neuroimmunological hypotheses have made some progress. The studies on neurotransmitters were mainly focused on serotonin butyric acid and glutamic acid. Neurodevelopmental related proteins, such as hepatocyte growth factor, nerve growth factor, and Reelin, have been studied deeply in neurodevelopmental hypothesis.
【作者单位】：中国医学科学院基础医学研究所&北京协和医学院基础学院医学分子生物学国家重点实验室;
【基金】：国家重点基础研究发展计划(批准号:2010CB529603)资助项目
【分类号】：R749.94

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