同卵雙胞胎的遺傳組成幾乎相同,，其表型特征以及患遺傳疾病的可能性也往往較一致,。但是有某些表型或疾病的發(fā)生——如自身免疫性疾病等,，在雙胞胎雙方中的發(fā)病情況有時是不同的，這表明除了遺傳因素以外，還有其它因素(如環(huán)境因素)在決定人的表型差異方面起重要作用。這篇研究報告發(fā)表在近期的Genome Research雜志上,。
目前，許多研究認為表觀遺傳修飾會影響表型以及疾病的發(fā)生率,。而且,，諸如飲食或接觸化學品等環(huán)境因素也能影響基因的表觀遺傳特征。最近一些對自身免疫疾病(如系統(tǒng)性紅斑狼瘡,SLE)的某些調(diào)控基因的研究表明,，遺傳組成相同的雙胞胎雙方,，其表型不一致與表觀遺傳學差異有關。
在這項研究中,，西班牙和美國的科學家首次利用全基因組高通量分析(genome-wide high-throughput analysis)對同卵雙胞胎一種特殊的表觀遺傳修飾——DNA甲基化進行研究,，通過對比雙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,，旨在通過雙方的表觀遺傳學差異找到患病一方的發(fā)病機理,。
通過對系統(tǒng)性紅斑狼瘡(SLE)的研究，課題組發(fā)現(xiàn)雙胞胎雙方大量基因的DNA甲基化水平不同,。
該研究作者Dr. Esteban Ballestar強調(diào),，到目前為止，這是在自身免疫性疾病中發(fā)現(xiàn)的最多的DNA甲基化改變,。這項研究還新發(fā)現(xiàn)大量的甲基化基因與多種免疫系統(tǒng)的功能有關,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
