打开APP

AJHG:鉴别出引发智力障碍的HUWE1蛋白质

  1. AJHG
  2. HUWE1
  3. 智力障碍
  4. 蛋白质

来源:生物谷 2012-11-18 15:03

2012年9月2日 讯 /生物谷BIOON/ --新生儿中大约有2%-3%的儿童从一出生就患上了智力障碍,这或许是由一种遗传缺失所致,但是在80%的发病例子中或许是由于某些基因“捣鬼”,近日,来自鲁汶大学的研究者揭示了蛋白质HUWE1产量的增加或许是某些智力障碍发病的原因。相关研究成果刊登在了国际杂志The American Journal of Human Genetics上。

2012年9月2日 讯 /生物谷BIOON/ --新生儿中大约有2%-3%的儿童从一出生就患上了智力障碍,这或许是由一种遗传缺失所致,但是在80%的发病例子中或许是由于某些基因“捣鬼”,近日,来自鲁汶大学的研究者揭示了蛋白质HUWE1产量的增加或许是某些智力障碍发病的原因。相关研究成果刊登在了国际杂志The American Journal of Human Genetics上。

HUWE1可以在大脑中调节许多蛋白质的表达,其对于新型治疗方法具有重要的意义,深入研究其功能对于理解智力障碍非常重要。智力障碍常常归咎于外部影响因子,如在出生时供养不足或者遗传物质缺失等。有将近15%的病人的致病原因是由于其X染色体的部分缺失,这就是所谓的X连锁智力障碍(XLID),尽管研究者在不断研究,但是引发XLID的效应基因至今仍没有被鉴别出来。

研究者Guy和其同事通过研究发现了引发XLID的新基因,在几年前,其发现X染色体片段的复制可以导致高浓度HSD17B10蛋白和HUWE1蛋白的产生,Guy教授说,这两种蛋白质在对于大脑记忆中枢非常关键,但是我们并不清楚到底是哪一种基因导致了XLID的病症。通过与欧洲、澳大利亚等处的研究人员共同研究,我们发现HUWE1是关键的因子,其浓度的增加可以导致智力障碍的发生。

研究者的研究为治疗XLID提供了新的思路,这也帮助我们检测HUWE1的复制以及错误发生,这项研究中,研究者的研究为我们更好地理解HUWE1蛋白提供了帮助,尤其是在大脑功能的角色扮演上更是提供了极大的帮助。(生物谷Bioon.com)

编译自:Too Much Protein HUWE1 Causes Intellectual Disability

Copy-Number Gains of HUWE1 Due to Replication- and Recombination-Based Rearrangements

Guy Froyen1, 2, , , Stefanie Belet1, 2, Francisco Martinez3, Cíntia Barros Santos-Rebouças4, Matthias Declercq1, 2, Jelle Verbeeck1, 2, Lene Donckers1, 2, Siren Berland5, 6, Sonia Mayo3, Monica Rosello3, Márcia Mattos Gonçalves Pimentel4, Natalia Fintelman-Rodrigues4, Randi Hovland6, Suely Rodrigues dos Santos7, F. Lucy Raymond8, Tulika Bose9, Mark A. Corbett9, Leslie Sheffield9, Conny M.A. van Ravenswaaij-Arts10, Trijnie Dijkhuizen10, Charles Coutton11, 12, 13, Veronique Satre11, 12, 13, Victoria Siu14 and Peter Marynen2

We previously reported on nonrecurrent overlapping duplications at Xp11.22 in individuals with nonsyndromic intellectual disability (ID) harboring HSD17B10, HUWE1, and the microRNAs miR-98 and let-7f-2 in the smallest region of overlap. Here, we describe six additional individuals with nonsyndromic ID and overlapping microduplications that segregate in the families. High-resolution mapping of the 12 copy-number gains reduced the minimal duplicated region to the HUWE1 locus only. Consequently, increased mRNA levels were detected for HUWE1, but not HSD17B10. Marker and SNP analysis, together with identification of two de novo events, suggested a paternally derived intrachromosomal duplication event. In four independent families, we report on a polymorphic 70 kb recurrent copy-number gain, which harbors part of HUWE1 (exon 28 to 3 untranslated region), including miR-98 and let-7f-2. Our findings thus demonstrate that HUWE1 is the only remaining dosage-sensitive gene associated with the ID phenotype. Junction and in silico analysis of breakpoint regions demonstrated simple microhomology-mediated rearrangements suggestive of replication-based duplication events. Intriguingly, in a single family, the duplication was generated through nonallelic homologous recombination (NAHR) with the use of HUWE1-flanking imperfect low-copy repeats, which drive this infrequent NAHR event. The recurrent partial HUWE1 copy-number gain was also generated through NAHR, but here, the homologous sequences used were identified as TcMAR-Tigger DNA elements, a template that has not yet been reported for NAHR. In summary, we showed that an increased dosage of HUWE1 causes nonsyndromic ID and demonstrated that the Xp11.22 region is prone to recombination- and replication-based rearrangements. /P>

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->