Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis

Sergio E. Baranzini, Joann Mudge, Jennifer C. Van Velkinburgh, Pouya Khankhanian, Irina Khrebtukova, Neil A. Miller, Lu Zhang, Andrew D. Farmer, Callum J. Bell, Ryan W. Kim, Gregory D. May, Jimmy E. Woodward, Stacy J. Caillier, Joseph P. McElroy, Refujia Gomez, Marcelo J. Pando, Leonda E. Clendenen, Elena E. Ganusova, Faye D. Schilkey, Thiruvarangan RamarajOmar A. Khan, Jim J. Huntley, Shujun Luo, Pui Yan Kwok, Thomas D. Wu, Gary P. Schroth, Jorge R. Oksenberg, Stephen L. Hauser, Stephen F. Kingsmore

Research output: Contribution to journalArticlepeer-review

363 Scopus citations


Monozygotic 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 pathogenesis1-8. However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture 9-12. 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.

Original languageEnglish (US)
Pages (from-to)1351-1356
Number of pages6
Issue number7293
StatePublished - Apr 29 2010

ASJC Scopus subject areas

  • General


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