Nature2014-06-26 2:06 PM

精神分裂症的致病机制2 A polygenic burden of rare disruptive mutations in schizophrenia

论文摘要 

本期Nature 发表了对精神分裂症患者及其亲属所做的两项重要外显子组(基因组的蛋白编码部分)测序研究。这两项研究一起为了解在精神分裂症中破坏谷氨酸能突触的特定致病机制提供了可靠线索。影响支架蛋白ARC(“活性调控的与细胞骨架相关的蛋白”)功能的突变在其中的参与尤为明显,“脆弱X智力迟钝蛋白” (FMRP)的目标中所发生的突变也是这样。FMRP的缺陷以前曾被发现与“泛自闭症”有关。

Abstract 

Schizophrenia is a common disease with a complex aetiology, probably involving multiple and heterogeneous genetic factors. Here, by analysing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we demonstrate a polygenic burden primarily arising from rare (less than 1 in 10,000), disruptive mutations distributed across many genes. Particularly enriched gene sets include the voltage-gated calcium ion channel and the signalling complex formed by the activity-regulated cytoskeleton-associated scaffold protein (ARC) of the postsynaptic density, sets previously implicated by genome-wide association and copy-number variation studies. Similar to reports in autism, targets of the fragile X mental retardation protein (FMRP, product of FMR1) are enriched for case mutations. No individual gene-based test achieves significance after correction for multiple testing and we do not detect any alleles of moderately low frequency (approximately 0.5 to 1 per cent) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene-mapping paradigms in neuropsychiatric disease.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

Nature

Nature Magazine

0 Following 27 Fans 0 Projects 626 Articles

SIMILAR ARTICLES

Meristems encompass stem/progenitor cells that sustain postembryonic growth of all plant organs. How meristems are activated and sustained by nutrient

Read More

Transcription of ribosomal RNA by RNA polymerase (Pol) I initiates ribosome biogenesis and regulates eukaryotic cell growth. The crystal structure of P

Read More

Abstract The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainti

Read More

Abstract Ecological and societal disruptions by modern climate change are critically determined by the time frame over which climates shift beyond his

Read More

Abstract Evidence from Greenland ice cores shows that year-to-year temperature variability was probably higher in some past cold periods, but there is

Read More

Abstract The land and ocean act as a sink for fossil-fuel emissions, thereby slowing the rise of atmospheric carbon dioxide concentrations1. Although t

Read More

论文摘要 人们已经非常清楚生物多样性对初级生产力等生态系统功能有一个积极影响,但它对植物凋落物的多样性和分解植物凋落物的生物的多样性的影响却不是很清楚。Stephan H?ttenschwiler及同事对从亚北极到热带、包括水生生态系统和陆地生态系统在内的五个地点所进行的并行操纵实验中的凋落物多样性进

Read More

论文摘要 FANTOM5 (即“哺乳动物基因组-5的功能注解”) 是一个大型国际合作项目的第5大阶段,其目标是分析定义每个人类细胞类型的转录调控网络。本期Nature上的两篇Articles论文发表了该项目的一些最新结果。第一篇论文利用FANTOM5项目组的组织和原代细胞样本来定义整个人体中活性的、在

Read More

论文摘要 有证据表明,血管 (尤其是它们的内皮细胞) 控制器官的生长、平衡和再生。在本期Nature上发表的两篇论文中,Ralf Adams及同事证明,骨头血管含有专门支持骨成熟和再生的内皮细胞。Anjali Kusumbe等人在小鼠骨骼系统内识别出一个在介导骨生长中起关键作用的毛细血管亚型。这些血管

Read More

论文摘要 CD4 T细胞(携带能够识别被病毒感染的细胞表面上的CD4抗原的受体的辅助T细胞)的丧失是艾滋病发病的根源。在这项研究中,Warner Greene等人识别出静止的淋巴CD4 T细胞在HIV感染过程中被耗尽的机制。利用保持了天然淋巴环境的人淋巴组织的体外培养,本文作者发现,失败的病毒复制触发

Read More