同卵双胞胎的遗传组成几乎相同,其表型特征以及患遗传疾病的可能性也往往较一致。但是有某些表型或疾病的发生——如自身免疫性疾病等,在双胞胎双方中的发病情况有时是不同的,这表明除了遗传因素以外,还有其它因素(如环境因素)在决定人的表型差异方面起重要作用。这篇研究报告发表在近期的Genome Research杂志上。
目前,许多研究认为表观遗传修饰会影响表型以及疾病的发生率。而且,诸如饮食或接触化学品等环境因素也能影响基因的表观遗传特征。最近一些对自身免疫疾病(如系统性红斑狼疮,SLE)的某些调控基因的研究表明,遗传组成相同的双胞胎双方,其表型不一致与表观遗传学差异有关。
在这项研究中,西班牙和美国的科学家首次利用全基因组高通量分析(genome-wide high-throughput analysis)对同卵双胞胎一种特殊的表观遗传修饰——DNA甲基化进行研究,通过对比双胞胎中正常的一方和患有自身免疫疾病(如SLE)的一方的DNA甲基化水平,旨在通过双方的表观遗传学差异找到患病一方的发病机理。
通过对系统性红斑狼疮(SLE)的研究,课题组发现双胞胎双方大量基因的DNA甲基化水平不同。
该研究作者Dr. Esteban Ballestar强调,到目前为止,这是在自身免疫性疾病中发现的最多的DNA甲基化改变。这项研究还新发现大量的甲基化基因与多种免疫系统的功能有关。(生物谷Bioon.com)
生物谷推荐原始出处:
Genome Research December 22, 2009, doi:10.1101/gr.100289.109
Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus
Biola M. Javierre1, Agustin F. Fernandez2, Julia Richter3, Fatima Al-Shahrour4,5,6, J. Ignacio Martin-Subero3, Javier Rodriguez-Ubreva1, Maria Berdasco2, Mario F. Fraga2, Terrance P. O'Hanlon7, Lisa G. Rider7, Filipe V. Jacinto2, F. Javier Lopez-Longo8, Joaquin Dopazo4,9, Marta Forn10, Miguel A. Peinado10, Luis Carre?o8, Amr H. Sawalha11,12,13, John B. Harley11,12,13, Reiner Siebert3, Manel Esteller2, Frederick W. Miller7 and Esteban Ballestar1,14
1Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain;
2Cancer Epigenetics Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain;
3Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Christian-Albrechts-University Kiel, Kiel D-24105, Germany;
4Bioinformatics Department, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain;
5Broad Institute, Cambridge, Massachusetts 02142, USA;
6Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Brookline, Massachusetts 02115, USA;
7Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, NIH, HHS, Bethesda, Maryland 20892, USA;
8Division of Rheumatology, Gregorio Mara?on Hospital, Madrid 28007, Spain;
9ISCIII Center for Biomedical Research on Rare Diseases, Valencia 46012, Spain;
10Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC), Badalona 08916, Spain;
11Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, 73104, USA;
12U.S. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, 73104, USA;
13Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.