Autism-associated gene expression in peripheral leucocytes commonly observed between subjects with autism and healthy women having autistic children.

Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although the numerous autism susceptible genes were identified, the etiology of autism is not fully explained. Using DNA microarray, we examined gene expression profiling in peripheral blood from 21 individuals in each of the four groups; young adults with ASD, age- and gender-matched healthy subjects (ASD control), healthy mothers having children with ASD (asdMO), and asdMO control. There was no blood relationship between ASD and asdMO. Comparing the ASD group with control, 19 genes were found to be significantly changed. These genes were mainly involved in cell morphology, cellular assembly and organization, and nerve system development and function. In addition, the asdMO group possessed a unique gene expression signature shown as significant alterations of protein synthesis despite of their nonautistic diagnostic status. Moreover, an ASD-associated gene expression signature was commonly observed in both individuals with ASD and asdMO. This unique gene expression profiling detected in peripheral leukocytes from affected subjects with ASD and unaffected mothers having ASD children suggest that a genetic predisposition to ASD may be detectable even in peripheral cells. Altered expression of several autism candidate genes such as FMR-1 and MECP2, could be detected in leukocytes. Taken together, these findings suggest that the ASD-associated genes identified in leukocytes are informative to explore the genetic, epigenetic, and environmental background of ASD and might become potential tools to assess the crucial factors related to the clinical onset of the disorder.

自闭症谱系障碍（ASD）是一种严重的神经精神疾病，其病理生物学复杂，在其发展过程中受遗传因素的深远影响。尽管已经确定了许多自闭症易感基因，但自闭症的病因尚未完全阐明。我们利用DNA微阵列技术，检测了四组中每组21个个体的外周血基因表达谱；患有ASD的年轻人、年龄和性别匹配的健康受试者（ASD对照）、有ASD患儿的健康母亲（asdMO）以及asdMO对照。ASD患者和asdMO之间没有血缘关系。将ASD组与对照组相比，发现有19个基因发生了显著变化。这些基因主要涉及细胞形态、细胞组装和组织以及神经系统发育和功能。此外，asdMO组具有独特的基因表达特征，尽管她们没有自闭症诊断，但表现为蛋白质合成的显著改变。而且，在ASD患者和asdMO中都普遍观察到一种与ASD相关的基因表达特征。在ASD患者和有ASD患儿的未患病母亲的外周白细胞中检测到的这种独特的基因表达谱表明，即使在外周细胞中也可能检测到ASD的遗传倾向。可以在外周白细胞中检测到几个自闭症候选基因如FMR - 1和MECP2的表达改变。综上所述，这些发现表明，在外周白细胞中鉴定出的与ASD相关的基因对于探索ASD的遗传、表观遗传和环境背景具有重要意义，并可能成为评估与该疾病临床发病相关的关键因素的潜在工具。