Douet Vanessa, Chang Linda, Cloak Christine, Ernst Thomas
Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96813, USA,
Brain Imaging Behav. 2014 Jun;8(2):234-50. doi: 10.1007/s11682-013-9260-1.
Human brain development has been studied intensively with neuroimaging. However, little is known about how genes influence developmental brain trajectories, even though a significant number of genes (about 10,000, or approximately one-third) in the human genome are expressed primarily in the brain and during brain development. Interestingly, in addition to showing differential expression among tissues, many genes are differentially expressed across the ages (e.g., antagonistic pleiotropy). Age-specific gene expression plays an important role in several critical events in brain development, including neuronal cell migration, synaptogenesis and neurotransmitter receptor specificity, as well as in aging and neurodegenerative disorders (e.g., Alzheimer disease or amyotrophic lateral sclerosis). In addition, the majority of psychiatric and mental disorders are polygenic, and many have onsets during childhood and adolescence. In this review, we summarize the major findings from neuroimaging studies that link genetics with brain development, from infancy to young adulthood. Specifically, we focus on the heritability of brain structures across the ages, age-related genetic influences on brain development and sex-specific developmental trajectories.
人们已经利用神经影像学对人类大脑发育进行了深入研究。然而,尽管人类基因组中大量基因(约10000个,约占三分之一)主要在大脑及大脑发育过程中表达,但对于基因如何影响大脑发育轨迹却知之甚少。有趣的是,许多基因除了在不同组织间表现出差异表达外,在不同年龄阶段也存在差异表达(例如拮抗多效性)。特定年龄的基因表达在大脑发育的几个关键事件中发挥着重要作用,包括神经元细胞迁移、突触形成和神经递质受体特异性,以及在衰老和神经退行性疾病(如阿尔茨海默病或肌萎缩侧索硬化症)中。此外,大多数精神疾病是多基因的,许多疾病在儿童期和青少年期发病。在这篇综述中,我们总结了神经影像学研究的主要发现,这些发现将遗传学与从婴儿期到青年期的大脑发育联系起来。具体而言,我们关注不同年龄阶段大脑结构的遗传性、与年龄相关的基因对大脑发育的影响以及性别特异性发育轨迹。