Nature Genetics：英德科学家发现新的肌肉修复基因MEGF10

naturalkillerce

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英德科学家发现新的肌肉修复基因MEGF10

6 o9 H( ], r5 S+ U+ F" jnaturalkillerce导语：英国利兹大学医学院和德国柏林夏洛蒂医科大学的研究人员通过采用最新的下一代DNA测序技术发现新的肌肉修复基因MEGF10，该基因在肌肉干细胞(muscle stem cell)上发挥着重要作用。肌肉干细胞也被称作卫星细胞，通常保持休眠状态。一旦肌纤维受损，卫星细胞变得活跃起来，开始分裂，然后与肌纤维融合。MEGF10通过提供黏性表面以便卫星细胞附着，在这种融合过程中发挥着重要作用。在日常生活当中，肌肉需要维持，而MEGF10也在这种肌肉再生过程发挥作用。现编译如下：" H6 S- ~" s0 J4 e# x- N) q$ M

" K$ m- b6 Z/ K4 L# U1 U' p2 @英国利兹大学(University of Leeds)医学院和德国柏林夏洛蒂医科大学(Charité, Berlin)的研究人员通过采用最新的下一代DNA测序技术，在几个家族---他们的孩子患有一种渐进性肌肉疾病(a progressive muscle disease)---中发现基因MEGF10存在缺陷。这些孩子身体肌肉和横隔膜---主要的呼吸肌---逐渐发展为严重性虚弱，这就使得这些孩子最终只能依赖轮椅和持续性机械通风。此外负责把食物从口往下运输到胃里的食管(esophagus)也不能正常工作，这些孩子只能通过鼻饲管喂食物。
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; m3 r8 C* f" i) |基因MEGF10正常情况下在肌肉干细胞(muscle stem cell)上发挥着重要作用。肌肉干细胞也被称作卫星细胞，这是因为它们附着在肌纤维的外表面上，而且保持休眠状态。一旦肌纤维受损，卫星细胞变得活跃起来，开始分裂，然后与肌纤维融合。MEGF10通过提供黏性表面以便卫星细胞附着，在这种融合过程中发挥着重要作用。
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' K; `2 M$ j; Q9 B0 I因为身体肌肉大约占据我们40%的体重，是人体最大的器官，在正常生活当中，这些肌肉需要维持。MEGF10也在这种肌肉再生过程发挥作用，不然再生失败将导致不仅导致躯干和四肢肌肉患上渐进性肌肉虚弱，也会导致在内部器官中发现的肌细胞患上渐进性肌肉虚弱。
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& X2 @+ K0 _$ Z( |. W- L2 l研究人员着重强调用于基因组分析的新方法的相关性。他们评论道，这些方法使得他们能够同时测序上百个甚至上千个基因，而且价格在可承受范围之内，这也使得临床医生和研究人员即便在单个病人身上也能发现新的遗传缺陷，这对于那些患有未知的罕见遗传疾病的家庭而言是个好新闻，很多受影响的病人和他们的父母---经常经历漫长诊断过程---如今可能希望他们患病的原因在不久的将来被查明。2 t$ @5 ?" `/ {

' J6 u( ^- E! a4 O6 d研究成果于2011年11月20日发表在Nature Genetics期刊上。0 X  I. }# |- e: o+ Y

  g" V) d& M. F5 i- ~* M原文信息：7 J8 @9 b5 Z- j5 \& ^9 _! T$ ?
Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD)
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Clare V Logan,         Barbara Lucke,         Caroline Pottinger,         Zakia A Abdelhamed,         David A Parry,         Katarzyna Szymanska,         Christine P Diggle,         Anne van Riesen,         Joanne E Morgan,         Grace Markham,         Ian Ellis, Adnan Y Manzur,         Alexander F Markham,         Mike Shires,         Tim Helliwell,         Mariacristina Scoto,         Christoph Hübner,         David T Bonthron,         Graham R Taylor,         Eamonn Sheridan,         Francesco Muntoni,         Ian M Carr, Markus Schuelke         & Colin A Johnson- D1 z7 O7 X1 J0 L4 v
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Nature Genetics (2011) Published online 20 November 2011
' c; c0 P, @0 N( i3 o  _6 M: Vdoi:10.1038/ng.995
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. f% |9 W1 j) w) z! I$ Q4 |http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.995.html+ z1 |6 q, f6 h9 V( [& B

naturalkillerce

回复 naturalkillerce 的帖子7 ?; e1 |8 d9 G" r3 G; U) Y& |
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New muscle repair gene discovered7 h& c; z: [0 j! M
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An international team of researchers from Leeds, London and Berlin has discovered more about the function of muscle stem cells, thanks to next-generation DNA sequencing techniques.
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The work, which was co-led from the University of Leeds' School of Medicine and the Charité, Berlin, is published this week in the journal Nature Genetics.4 ?) l9 t+ E' `: W/ E2 B; r, Y
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The researchers investigated several families whose children suffered from a progressive muscle disease. The children developed severe weakness of the body's muscles and the diaphragm - the main breathing muscle - making them dependent on a wheelchair and continuous mechanical ventilation. The children also had to be tube-fed because the esophagus - a muscular tube that transports food from the mouth down into the stomach - did not work properly.& z5 U& n# M! \9 W  O
Using state-of the-art, next generation DNA sequencing technology, the scientists initially found a defect in the MEGF10 gene for a large family living in the UK. Further work found mutations in families with a similar condition from Europe and Asia.
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3 ~' U( Q& E0 }& M3 L( KTheir work means that accurate genetic testing and diagnosis will now be possible for this devastating condition.+ b9 X- e& }6 q* V
The MEGF10 gene normally plays an important function in muscle stem cells. These are also called 'satellite cells', because they are attached to the outer surface of the muscle fibres, where they normally remain silent. If a muscle fibre becomes damaged, the satellite cells become active, start to divide and then fuse with the muscle fibre. MEGF10 has an important role in this fusion process because it provides the 'gluey' surface for the attachment of the satellite cell.
' }9 b3 d) t2 aSince body muscles make up about 40% of our weight and are the largest organ in the body, the muscles need to be maintained during normal life. MEGF10 also has a role in this regeneration process; failure causes progressive muscle weakness in not only muscles of the body and limbs but also the muscle cells that can be found in the internal organs.6 N/ h) i% v: A0 h* m5 _

9 s6 H0 Q& P6 G$ V* ~, ~The project's joint directors, Professor Markus Schuelke from the NeuroCure Clinical Research Center and the Department of Neuropediatrics of the Charité, and Professor Colin A. Johnson from the Leeds Institute of Molecular Medicine, University Leeds, emphasized the relevance of the new methods for genomic analysis. They commented: "These methods enable us to sequence hundreds or even thousands of genes at the same time for an affordable price. This enables clinicians and researchers to discover novel genetic defects even in single patients. This is good news for families with unsolved rare genetic disorders. Many affected patients and their parents, who often have a "diagnostic Odyssey" behind them, may now hope that the cause of their disease will be found in the near future."5 d* E& w3 F4 w: D- s0 l; L; n
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http://medicalxpress.com/news/2011-11-muscle-gene.html, f* O  k% j& {2 T  V

goodboy

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: ~  K* a. s3 X5 C第一篇文献

wys7416

是否可以用转基因的方法，携带这种基因，去修复这种肌肉萎缩，重新激活卫星细胞，使其开始分裂，然后与肌纤维融合？如果可以的话，那么MEGF10基因确实可以通过提供黏性表面以便卫星细胞附着，在这种融合过程中发挥着重要作用。或者在体外可以验证一下，是否可行，如果可行，那将真是一个福音！

naturalkillerce

回复 wys7416 的帖子
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与其用转基因技术，还不如用ZFNs或TALENS进行基因组编辑来修复这种基因。