Autism and environmental genomics
Autism and environmental genomics
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DOI：
10.1016/j.neuro.2006.03.017
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发表时间：
2006-09-01
期刊：
影响因子：
3.4
通讯作者：
Hatchwell, E.
中科院分区：
文献类型：
--
作者：
Herbert, M. R.;Russo, J. P.;Hatchwell, E.
自闭症谱系障碍（ASD）的定义是行为和诊断的临床病史和观察，但没有生物标志物，并推测，病因学和生物学异质性。鉴于大脑异常和高单合子一致性，ASD已被框定为基于神经生物学和高度遗传的，这塑造了研究议程，特别是选择候选ASD基因的标准。迄今为止，遗传学研究还没有发现具有强烈影响的基因，但在神经生物学水平上朝着“遗传复杂性”的方向发展可能还不够，因为系统异常（例如胃肠道和免疫）的证据，增加的比率和不到100%的单合子一致性支持自闭症作为一种具有遗传影响和环境因素的多系统疾病的更具包容性的抑制。我们回顾了这些证据，并使用生物信息学的方法来探索这种可能性，即“环境响应基因”与神经系统无关，但可能与自闭症的系统性变化有关，迄今为止在自闭症遗传学研究中尚未得到足够的重视。我们将来自NIEHS环境基因组计划、比较毒理基因组学数据库和西雅图SNP数据库的与人类免疫和炎症反应相关的基因与已发表的自闭症基因组扫描中确定的连锁区域重叠。我们在重叠区域确定了135个基因，其中56个以前从未被研究过与自闭症有关，47个具有功能性SNP（在编码区）。我们的综述和生物信息学研究都支持扩大评估基因与自闭症风险相关性的标准，以包括与系统影响和环境反应相关的基因。这篇评论还建议利用环境基因组资源，突出潜在的关联区域内的特定基因。因此，在确定自闭症中基因-环境相互作用的众多复杂模式时，支持将与自闭症全系统研究结果一致的环境反应性和系统影响作为重要考虑因素。(C)2006年爱思唯尔公司All rights reserved.
Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical history and observation but have no biomarkers and are presumably, etiologically and biologically heterogeneous. Given brain abnormalities and high monozygotic concordance, ASDs have been framed as neurobiologically based and highly genetic, which has shaped the research agenda and in particular criteria for choosing candidate ASD genes. Genetic studies to date have not uncovered genes of strong effect, but a move toward "genetic complexity" at the neurobiological level may not suffice, as evidence of systemic abnormalities (e.g. gastrointestinal and immune), increasing rates and less than 100% monozygotic concordance support a more inclusive refraining of autism as a multisystern disorder with genetic influence and environmental contributors. We review this evidence and also use a bioinformatic approach to explore the possibility that "environmentally responsive genes" not specifically associated with the nervous system, but potentially associated with systemic changes in autism, have not hitherto received sufficient attention in autism genetics investigations. We overlapped genes from NIEHS Environmental Genome Project, the Comparative Toxicogenomics Database, and the SeattleSNPs database of genes relevant to the human immune and inflammatory response with linkage regions identified in published autism genome scans. We identified 135 genes in overlap regions, of which 56 had never previously been studied in relation to autism and 47 had functional SNPs (in coding regions). Both our review and the bioinformatics exercise support the expansion of criteria for evaluating the relevance of genes to autism risk to include genes related to systemic impact and environmental responsiveness. This review also suggests the utility of environmental genomic resources in highlighting the potential relevance of particular genes within linkage regions. Environmental responsiveness and systems impacts consistent with system-wide findings in autism are thus supported as important considerations in identifying the numerous and complex modes of gene-environment interaction in autism. (C) 2006 Elsevier Inc. All rights reserved.