Alzheimers Dement:昆明动物所阿尔茨海默病基因表达谱与调控网络研究获进展

2017-09-28 昆明动物所 中国生物技术网

近日,中国科学院昆明动物研究所姚永刚课题组的研究论文A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease 发表在Alzheime

近日,中国科学院昆明动物研究所姚永刚课题组的研究论文A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease 发表在Alzheimer's & Dementia 杂志上。该研究利用整合分析的方法,总结了阿尔茨海默病(Alzheimer's disease, AD)的脑组织基因表达谱及其遗传易感基因名录,并搭建了AlzData (www.alzdata.org) 数据库,以促进AD研究领域相关数据的共享和利用。

AD(俗称老年痴呆)是发生在老年前期与老年期的一种常见的神经退行性脑病,主要表现为认知和记忆功能逐渐丧失。其发病率随着年龄增长而显着增加。随着世界老龄化进程的加剧,全世界的AD患者数量急剧增长。在我国,AD导致的社会经济负担日益沉重。除年龄外,AD发病同时受遗传、环境和生活方式等影响,其中遗传因素是AD最重要的风险因子之一。前人通过连锁分析发现,早发家族型AD的风险基因APP、PSEN1和PSEN2,而近期的大规模全基因组关联分析(genome-wide association studies, GWASs)则发现,约20个晚发散发型AD的遗传易感基因。AD的遗传研究近年来取得了巨大进展,但遗传风险如何影响AD的发生发展,目前尚不完全清楚。

基因表达是一种介于基因型(genotype)和表型(phenotype)之间重要的中间表型。现有GWAS发现的疾病风险位点约80%都位于基因组非编码区,这些位点很可能是通过调控基因表达,影响机体正常的基因调控网络,进而影响疾病的发生发展。因此,对AD表达谱的研究,能够增加我们对于AD遗传变异与AD发生之间关联的理解,并有望发现新的生物学标记和潜在的治疗分子靶标。现有的AD表达谱分析,由于采用的数据收集分析平台差异、样本数大小不同等问题,得到的结果不尽相同。在姚永刚指导下,昆明动物所博士研究生徐敏和博士张登峰等对报道的AD脑组织表达谱数据进行了全面系统的整合分析,以探究AD发展过程中基因表达谱及调控网络的改变,寻找AD发生过程中起关键节点作用的上游调控因子。研究人员收集了目前为止最大的AD相关脑区表达数据集并进行整合分析,获得了稳健的AD差异表达基因集,构建了精细的AD调控网络。利用涵盖多个AD相关组学数据,如GWAS数据、大脑eQTL数据、蛋白-蛋白相互作用预测数据以及AD小鼠模型数据等,研究人员进一步开展了趋同功能基因组(convergent functional genomics, CFG)分析,筛选得到在AD调控网络中的核心基因,以及在疾病发生早期起关键调控节点作用的上游调控因子,如发现Hippo信号通路重要的转录共激活因子YAP1。进一步功能实验表明,上游调控因子YAP1表达水平的变化,能够扰乱整个表达调控网络,从而促进AD的发生发展。该研究提示,在AD发病初期对上游调控因子进行干预,可能会是减缓或逆转AD发展的一种手段。同时,研究人员搭建了AD表达数据库AlzData,将整合分析的结果全部展示,便于查询,以促进AD领域的数据共享与利用。

研究得到国家自然科学基金委、中科院脑功能联结图谱先导专项和中科院前沿重点研究项目的资助。

原始出处:
Xu M, Zhang DF, Luo R, et al.A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease.Alzheimers Dement. 2017 Sep 15. pii: S1552-5260(17)33707-X. doi: 10.1016/j.jalz.2017.08.012. [Epub ahead of print]

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CST 2018, time=2018-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338463, encodeId=b3501338463a3, content=<a href='/topic/show?id=767711566a9' target=_blank style='color:#2F92EE;'>#MERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11566, encryptionId=767711566a9, topicName=MERS)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/71tKRib0PibveVjnEa7tPLMaCzoKicFlKSEOzRTGf4wNvDV54kJyNx1ott1D5Xp5gRu7IwUia77oN0YFdffvQMu6Ug/132, createdBy=9e302500146, createdName=ms49895894946433513521, createdTime=Sat Sep 30 01:51:00 CST 2017, time=2017-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348043, encodeId=138b134804372, content=<a href='/topic/show?id=d61b418860a' target=_blank style='color:#2F92EE;'>#基因表达#</a>, beContent=null, objectType=article, channel=null, level=null, 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  4. [GetPortalCommentsPageByObjectIdResponse(id=1816803, encodeId=13781816803ab, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Tue Dec 19 00:51:00 CST 2017, time=2017-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1801232, encodeId=4a0f1801232df, content=<a href='/topic/show?id=d4bce344265' target=_blank style='color:#2F92EE;'>#研究获进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, 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CST 2018, time=2018-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338463, encodeId=b3501338463a3, content=<a href='/topic/show?id=767711566a9' target=_blank style='color:#2F92EE;'>#MERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11566, encryptionId=767711566a9, topicName=MERS)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/71tKRib0PibveVjnEa7tPLMaCzoKicFlKSEOzRTGf4wNvDV54kJyNx1ott1D5Xp5gRu7IwUia77oN0YFdffvQMu6Ug/132, createdBy=9e302500146, createdName=ms49895894946433513521, createdTime=Sat Sep 30 01:51:00 CST 2017, time=2017-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348043, encodeId=138b134804372, content=<a href='/topic/show?id=d61b418860a' target=_blank style='color:#2F92EE;'>#基因表达#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41886, encryptionId=d61b418860a, topicName=基因表达)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=bioon1, createdTime=Sat Sep 30 01:51:00 CST 2017, time=2017-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470179, encodeId=e9c214e01797e, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Sat Sep 30 01:51:00 CST 2017, time=2017-09-30, status=1, ipAttribution=)]
    2018-05-25 anminleiryan
  5. 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  6. 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  7. 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  8. 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  9. 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