生物谷报道：在哮喘基因方面有很多报道，但没有一个能够清楚表明实验的可重复性。最近，科学家发现一种新的基因，它与儿童期发作性哮喘有很强的关系。这些发现发表在《自然》杂志上。
本研究的对象是1958年出生的2000多德国儿童和3000多英国人。研究者一直观察他们患哮喘的情况。通过分析他们的基因组成，研究者证实了这项发现。密歇根大学的科学家和来自伦敦、法国和德国的同行们比较了994位儿童哮喘患者和1243位未患哮喘者的基因组成。他们观察组成DNA的核苷的变化。大约每600个核苷就有一个发生改变，科学家检测了31万7千多个这种核苷，即单一核苷多态现象，看这些变化与儿童哮喘是否有关。研究者也观察基因是如何在人类血细胞内表达的。最终科研人员发现的遗传标记位于染色体17，它能够显著增加儿童发生哮喘的风险。有这种标记的儿童血液中有新的基因――ORMDL3，它在哮喘儿童中的出现几率更大。本研究显示，ORMDL3的出现能使患哮喘的几率增加60－70％。
这些新奇的发现没能完全解释哮喘是如何发生的，但是它们能进一步说明导致哮喘的基因和环境因素。研究人员正准备做更大的研究，来找到导致其他轻微症状的基因，并把这些基因与增加发病风险的环境因素相联系。这项研究成果最终可能会带来新的治疗方案，因为它指出了一条新的生物分子方向。一旦理解了其生物学机制和参与的物质，科研人员就可能研制出特效药。
FIGURE 1. Study design.
The subjects were recruited from family (MRC-A) and case-control panels (MAGICS and UK-C). All children were genotyped with the Illumina Sentrix HumanHap300 BeadChip. The children and parents in the MRC-A panel were in addition genotyped with the Illumina Sentrix Human-1 Genotyping BeadChip. Gene expression in lymphoblastoid cell lines (EBVL) was measured in the affected and unaffected children of the MRC-A panel. Replication of positive results was sought in two independent panels of subjects from the ISAAC Phase II and 1958 British Birth Cohort studies.
原文出处：
Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma
Miriam F. Moffatt, Michael Kabesch, Liming Liang, Anna L. Dixon, David Strachan, Simon Heath, Martin Depner, Andrea von Berg, Albrecht Bufe, Ernst Rietschel, Andrea Heinzmann, Burkard Simma, Thomas Frischer, Saffron A. G. Willis-Owen, Kenny C. C. Wong, Thomas Illig, Christian Vogelberg, Stephan K. Weiland, Erika von Mutius, Gonçalo R. Abecasis, Martin Farrall, Ivo G. Gut, G. Mark Lathrop, William O. C. Cookson
Nature (04 Jul 2007) Letters to Editor
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作者简介：
Professor William O.C. Cookson
Professor Bill Cookson, Professor of Respiratory Genetics, presented his professorial lecture: “Adventures in the Genome Jungle”.
Abstract:
Asthma and Atopic Dermatitis run strongly in families and are due to the combination of poorly understood genetic and environmental factors. Genetic studies have identified susceptibility factors for both illnesses that appear to be acting at epithelial surfaces, and appear to influence innate rather than adaptive immunity. The completion of the human genome sequencing project and advances in technology have made it possible to examine simultaneously the expression of all human genes and to test for the presence of hundreds of thousands of genetic variants in a single experiment. The application of these tools has the potential for great advances in the understanding of disease, but equally carries the potential for confusion and error whilst investigators struggle with a deluge of data. The lecture will describe post-genome investigations of asthma and atopic dermatitis, with whole genome association studies, expression quantitative trait mapping, and the systematic dissection of airway inflammation in model systems.
Biography:
Professor William Cookson was appointed Professor of Respiratory Genetics at Imperial College London in October 2004. He was previously Professor of Human Genetics at the University of Oxford. Originally a respiratory physician, he developed a research group over 20 years with Dr Miriam Moffatt to investigate the genetic causes of asthma and atopic dermatitis. Their molecular genetics group at the National Heart and Lung Institute is supported by several large grants which include a Wellcome Trust programme grant, and the EU FP6 funded GABRIEL integrated project. GABRIEL was set up to investigate the genetic and environmental cause of asthma within the European community, and is co-ordinated by Professor Cookson and Professor Erika von Mutius at the University of Munich. Current projects in the molecular genetic group include whole-genome association mapping, and the development of genomic models for the systematic investigation of airway inflammation.
Moffatt, M F
Publications
Dr Miriam F Moffatt
Reader in Respiratory Genetics
National Heart and Lung Institute
Working in research themes:
Heart and Lung
This person linked with:
Academic
Molecular Genetics (Group)
