新一期英国《自然》杂志报告说，一项双胞胎对比研究发现，多发性硬化症并不完全受基因因素控制。
此前的研究曾认为，多发性硬化症是一种遗传性疾病，是否患病，完全由人体内的基因组决定。
为了验证这项结论，美国加利福尼亚大学等机构研究人员选择一对女性双胞胎进行研究。双胞胎其中一人患有多发性硬化症，另一人完全健康。研究人员对这对姐妹进行了完整基因组测序。对比结果发现，两人基因组没有重大差异。
研究人员认为，这个结果表明，多发性硬化症并不完全受基因控制。从基因角度来说，这对双胞胎出生时的患病风险是完全相同的，但后来只有一人发病，另一人保持健康。这说明除了基因因素以外，多发性硬化症发病肯定还受到外界环境因素等的影响。
多发性硬化症是一种神经系统疾病，患者自身免疫细胞会错误攻击神经元髓鞘，造成患者出现视觉障碍、肌肉无力等症状。
更多阅读
《自然》网站相关报道（英文）
《自然》发表论文摘要（英文）
Nature 464, 1351-1356 (29 April 2010) | doi:10.1038/nature08990; Received 25 July 2009; Accepted 11 March 2010
Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
Sergio E. Baranzini1, Joann Mudge2, Jennifer C. van Velkinburgh2, Pouya Khankhanian1, Irina Khrebtukova3, Neil A. Miller2, Lu Zhang3, Andrew D. Farmer2, Callum J. Bell2, Ryan W. Kim2, Gregory D. May2, Jimmy E. Woodward2, Stacy J. Caillier1, Joseph P. McElroy1, Refujia Gomez1, Marcelo J. Pando4, Leonda E. Clendenen2, Elena E. Ganusova2, Faye D. Schilkey2, Thiruvarangan Ramaraj2, Omar A. Khan5, Jim J. Huntley3, Shujun Luo3, Pui-yan Kwok6,7, Thomas D. Wu8, Gary P. Schroth3, Jorge R. Oksenberg1,7, Stephen L. Hauser1,7 " Stephen F. Kingsmore2
Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
Sergio E. Baranzini1, Joann Mudge2, Jennifer C. van Velkinburgh2, Pouya Khankhanian1, Irina Khrebtukova3, Neil A. Miller2, Lu Zhang3, Andrew D. Farmer2, Callum J. Bell2, Ryan W. Kim2, Gregory D. May2, Jimmy E. Woodward2, Stacy J. Caillier1, Joseph P. McElroy1, Refujia Gomez1, Marcelo J. Pando4, Leonda E. Clendenen2, Elena E. Ganusova2, Faye D. Schilkey2, Thiruvarangan Ramaraj2, Omar A. Khan5, Jim J. Huntley3, Shujun Luo3, Pui-yan Kwok6,7, Thomas D. Wu8, Gary P. Schroth3, Jorge R. Oksenberg1,7, Stephen L. Hauser1,7 " Stephen F. Kingsmore2
Department of Neurology, University of California at San Francisco, San Francisco, California 94143, USA
National Center for Genome Resources, Santa Fe, New Mexico 87505, USA
Illumina Inc., Hayward, California 94545, USA
Stanford Medical School Blood Center, Palo Alto, California 94303, USA
Department of Neurology, Wayne State Medical School, Detroit, Michigan 48201, USA
Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94143, USA
Institute for Human Genetics, University of California at San Francisco, San Francisco, California 94143, USA
Department of Bioinformatics, Genentech Inc., South San Francisco, California 94080, USA
Correspondence to: Sergio E. Baranzini1 Email: sebaran@cgl.ucsf.edu
Correspondence to: Stephen F. Kingsmore2 Email: sfk@ncgr.org
Top of pageAbstractMonozygotic or ‘identical’ twins have been widely studied to dissect the relative contributions of genetics and environment in human diseases. In multiple sclerosis (MS), an autoimmune demyelinating disease and common cause of neurodegeneration and disability in young adults, disease discordance in monozygotic twins has been interpreted to indicate environmental importance in its pathogenesis1, 2, 3, 4, 5, 6, 7, 8. However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture9, 10, 11, 12. Here we report the genome sequences of one MS-discordant monozygotic twin pair, and messenger RNA transcriptome and epigenome sequences of CD4+ lymphocytes from three MS-discordant, monozygotic twin pairs. No reproducible differences were detected between co-twins among ~3.6 million single nucleotide polymorphisms (SNPs) or ~0.2 million insertion-deletion polymorphisms. Nor were any reproducible differences observed between siblings of the three twin pairs in HLA haplotypes, confirmed MS-susceptibility SNPs, copy number variations, mRNA and genomic SNP and insertion-deletion genotypes, or the expression of ~19,000 genes in CD4+ T cells. Only 2 to 176 differences in the methylation of ~2 million CpG dinucleotides were detected between siblings of the three twin pairs, in contrast to ~800 methylation differences between T cells of unrelated individuals and several thousand differences between tissues or between normal and cancerous tissues. In the first systematic effort to estimate sequence variation among monozygotic co-twins, we did not find evidence for genetic, epigenetic or transcriptome differences that explained disease discordance. These are the first, to our knowledge, female, twin and autoimmune disease individual genome sequences reported.
