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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Comparative genomics of autism and schizophrenia
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Comparative genomics of autism and schizophrenia

机译：自闭症和精神分裂症的比较基因组学

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We used data from studies of copy-number variants (CNVs), single-gene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (ⅰ) autism subsumed in schizophrenia, (ⅱ) independence, (ⅲ) diametric, and (ⅳ) partial overlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance. However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia. Evidence from the effects of risk variants on growth-signaling pathways shows that autism-spectrum conditions tend to be associated with up-regulation of pathways due to loss of function mutations in negative regulators, whereas schizophrenia is associated with reduced pathway activation. Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with, developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth. These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurode-velopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain.
机译：我们使用了与拷贝数变异（CNV），单基因关联，生长信号通路和与大脑生长相关的中间表型的研究数据，以评估自闭症和精神分裂症之间的基因组和发育关系的四种替代假设：自闭症包括精神分裂症，（ⅱ）独立性，（ⅲ）直径和（metric）部分重叠。来自CNV的数据为自闭症和精神分裂症与互易变异相关的假说提供了统计依据，例如，在四个基因座处，缺失易患一种疾病，而重复则易患另一种疾病。来自单基因研究的数据与基于独立性的假设不一致，因为自闭症和精神分裂症比偶然的机会更多地共享相关基因。然而，由于在自闭症和精神分裂症中分析的特定遗传标志物的有限重叠，排除了使用这些数据进行部分重叠和径向假设之间的区别。风险变体对生长信号通路的影响的证据表明，自闭症患者的频谱状况往往与负调节剂中功能突变的丧失有关，而与通路的上调有关，而精神分裂症则与通路激活的减少有关。最后，来自头部和大脑大小表型研究的数据表明，自闭症通常与脑部发育增强有关，而精神分裂症的平均特征是脑部生长减少。这些趋同的证据线似乎与自闭症和精神分裂症在其基因组基础，神经发育基础和表型表现代表着人类疾病的直觉条件最相符，这些假说反映了人类社会大脑的发育不足与失调过度发育。

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