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Nat Genet:这个基因竟与四种罕见神经退行性疾病都有关

2019-07-28 苏煜静 生物探索

神经退行性疾病一直是医学研究难以攻克的一大疾病,像是阿尔茨海默症、帕金森、癫痫、亨廷顿病等都是我们所熟悉的神经退行性疾病。当然,对于一些罕见的神经退行性疾病科学家也没有放弃。同一种疾病可能是由于不同的基因突变导致的,这就使得许多遗传性疾病治疗变得复杂。如果能够找到其中的共同点,或将为治疗带来新方法。

神经退行性疾病一直是医学研究难以攻克的一大疾病,像是阿尔茨海默症、帕金森、癫痫、亨廷顿病等都是我们所熟悉的神经退行性疾病。当然,对于一些罕见的神经退行性疾病科学家也没有放弃。同一种疾病可能是由于不同的基因突变导致的,这就使得许多遗传性疾病治疗变得复杂。如果能够找到其中的共同点,或将为治疗带来新方法。

近日,日本东京大学的研究人员们在《Nature Genetics》杂志发表论文称,同一个基因在四种不同的罕见神经退行性疾病患者身上均出现重复扩增的现象。

这个基因或是罕见病的罪魁祸首

神经元核内包涵体疾病(NIID)是一种罕见的神经退行性疾病。患者表现出认知障碍、运动失控、失去平衡、四肢无力或是吞咽困难等症状。不久前在《American Journal of Human Genetics》上发表的一篇研究中,名古屋大学医学研究生院神经学教授Gen Sobue的研究团队通过对8个家庭13名受NIID影响个体和4个未受影响个体的分析发现,NIID与X染色体上的遗传密码子CGG会重复有关,首次揭示了DNA序列重复与神经退行性疾病之间的关系。

而在由东京大学医学助理教授Hiroyuki Ishiura和他的同事发表的最新研究中,他们进一步调查了四个患有NIID疾病的家族。研究人员对四组家庭成员进行基因检测,依靠短序列读取与智能数据(一种新的“TRhist”程序)分析相结合的方法,生成包含串联重复序列的段读取直方图。经分析发现只有在患者的基因组中出现了CGG重复扩增的现象。

高科技清道夫助力研究分析

在人类46条染色体上搜索CGG重复突变对于传统DNA测序技术而言是相当困难的,此次Ishiura教授所在团队的研究人员设计了一种新方法,借助新一代基因组测序并新开发出一种名为“TRhist”的计算机程序进行智能数据分析。

研究人员对患者和健康人的整个基因组进行了测序,通过TRhist对所有短序列进行排序,并一遍又一遍地搜索由CGG组成的序列。再对比健康人类基因组的标准序列,计算机程序可以将包含CGG重复突变的那些短片段定位到染色体区域。

如此一来,研究人员便能将他们的搜索范围缩小到基因组中的任何地方,在这一染色体区域内只有患者有大量的CGG重复,而健康的人没有。

有了这些信息,研究人员就会知道对哪些染色体区域进行测序,来明确检测这些区域内的基因以及CGG重复突变在这些基因中的具体位置。

CGG重复扩增与其他三种罕见病有关

由于NIID与伴有白质脑病(OPML)的眼咽病、眼咽肌病(OPDM)和眼咽肌营养不良症(OPMD)这三种罕见的神经退行性疾病具有相似的症状和临床检测结果,因此研究人员预测:相同的CGG重复突变可能会导致其他三种罕见的疾病。为了验证这一猜想,Ishiura教授和他的同事也采用了同样的方法来寻找其他相关疾病相关基因的重复扩增。



四种罕见疾病的特征在于神经变性的相似症状

研究结果表明,CGG基因的重复扩增对另外三种神经系统疾病也有很大影响,并且由于许多重复相似,单一治疗可能针对多种疾病。

结语

Ishiura教授所在团队研究发现所有四种罕见的神经系统疾病都是由CGG相隔较远的、看似无关的基因组区域内重复突变引起的。

其中一种疾病目前只在一个家庭中发现。Ishiura教授说:“我们在十年前就已经开始注意到这个家庭,对我们来说,找到正确的诊断方法是一个长期努力的方向。”

研究人员希望,他们对罕见神经退行性疾病的研究,可能会对其他类型的非编码串联重复突变引起的更常见的疾病有更深的了解。

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    2019-09-21 cy0324
  4. [GetPortalCommentsPageByObjectIdResponse(id=1735395, encodeId=c80b1e35395c9, content=<a href='/topic/show?id=740394686b2' target=_blank style='color:#2F92EE;'>#退行性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94686, encryptionId=740394686b2, topicName=退行性疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5a0233899115, createdName=ZGMFX35A, createdTime=Thu Nov 28 21:18:00 CST 2019, time=2019-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1957171, encodeId=a83d195e17146, content=<a href='/topic/show?id=5879e458629' target=_blank style='color:#2F92EE;'>#神经退行#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74586, encryptionId=5879e458629, topicName=神经退行)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=33b92500139, createdName=12498b37m72暂无昵称, createdTime=Thu Jul 02 17:18:00 CST 2020, time=2020-07-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049213, encodeId=071d204921377, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat Sep 21 19:18:00 CST 2019, time=2019-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1686301, encodeId=9fd41686301e4, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e128296421, createdName=江川靖瑶, createdTime=Wed Aug 28 12:18:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883802, encodeId=73fe1883802f6, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Sep 23 00:18:00 CST 2019, time=2019-09-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734157, encodeId=43631e341575a, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Sat Mar 14 08:18:00 CST 2020, time=2020-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1467473, encodeId=7e9d146e4731a, content=<a href='/topic/show?id=ef32e9539e8' target=_blank style='color:#2F92EE;'>#罕见#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79539, encryptionId=ef32e9539e8, topicName=罕见)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=29f36868190, createdName=syscxl, createdTime=Tue Jul 30 13:18:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=370437, encodeId=8c4f3e043780, content=向科研人员致敬!, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5171668917, createdName=坚强007, createdTime=Mon Jul 29 09:10:11 CST 2019, time=2019-07-29, status=1, ipAttribution=)]
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    2019-09-23 liye789132251
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    2020-03-14 canlab
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    2019-07-30 syscxl
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    2019-07-29 坚强007

    向科研人员致敬!

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