生物谷報道：在哮喘基因方面有很多報道，但沒有一個能夠清楚表明實驗的可重復(fù)性,。最近,，科學(xué)家發(fā)現(xiàn)一種新的基因,，它與兒童期發(fā)作性哮喘有很強的關(guān)系。這些發(fā)現(xiàn)發(fā)表在《自然》雜志上,。
本研究的對象是1958年出生的2000多德國兒童和3000多英國人,。研究者一直觀察他們患哮喘的情況。通過分析他們的基因組成,，研究者證實了這項發(fā)現(xiàn),。密歇根大學(xué)的科學(xué)家和來自倫敦、法國和德國的同行們比較了994位兒童哮喘患者和1243位未患哮喘者的基因組成,。他們觀察組成DNA的核苷的變化,。大約每600個核苷就有一個發(fā)生改變，科學(xué)家檢測了31萬7千多個這種核苷,，即單一核苷多態(tài)現(xiàn)象,，看這些變化與兒童哮喘是否有關(guān)。研究者也觀察基因是如何在人類血細胞內(nèi)表達的,。最終科研人員發(fā)現(xiàn)的遺傳標(biāo)記位于染色體17,，它能夠顯著增加兒童發(fā)生哮喘的風(fēng)險。有這種標(biāo)記的兒童血液中有新的基因――ORMDL3,，它在哮喘兒童中的出現(xiàn)幾率更大,。本研究顯示，ORMDL3的出現(xiàn)能使患哮喘的幾率增加60－70％,。
這些新奇的發(fā)現(xiàn)沒能完全解釋哮喘是如何發(fā)生的,，但是它們能進一步說明導(dǎo)致哮喘的基因和環(huán)境因素。研究人員正準備做更大的研究,，來找到導(dǎo)致其他輕微癥狀的基因，并把這些基因與增加發(fā)病風(fēng)險的環(huán)境因素相聯(lián)系,。這項研究成果最終可能會帶來新的治療方案，因為它指出了一條新的生物分子方向,。一旦理解了其生物學(xué)機制和參與的物質(zhì),，科研人員就可能研制出特效藥,。
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.
原文出處：
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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作者簡介：
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)
