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

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...

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Autores principales: Baranzini, Sergio E., Mudge, Joann, van Velkinburgh, Jennifer C., Khankhanian, Pouya, Khrebtukova, Irina, Miller, Neil A., Zhang, Lu, Farmer, Andrew D., Bell, Callum J., Kim, Ryan W., May, Gregory D., Woodward, Jimmy E., Caillier, Stacy J., McElroy, Joseph P., Gomez, Refujia, Pando, Marcelo J., Clendenen, Leonda E., Ganusova, Elena E., Schilkey, Faye D., Ramaraj, Thiruvarangan, Khan, Omar A., Huntley, Jim J., Luo, Shujun, Kwok, Pui-yan, Wu, Thomas D., Schroth, Gary P., Oksenberg, Jorge R., Hauser, Stephen L., Kingsmore, Stephen F.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862593/
https://www.ncbi.nlm.nih.gov/pubmed/20428171
http://dx.doi.org/10.1038/nature08990
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author Baranzini, Sergio E.
Mudge, Joann
van Velkinburgh, Jennifer C.
Khankhanian, Pouya
Khrebtukova, Irina
Miller, Neil A.
Zhang, Lu
Farmer, Andrew D.
Bell, Callum J.
Kim, Ryan W.
May, Gregory D.
Woodward, Jimmy E.
Caillier, Stacy J.
McElroy, Joseph P.
Gomez, Refujia
Pando, Marcelo J.
Clendenen, Leonda E.
Ganusova, Elena E.
Schilkey, Faye D.
Ramaraj, Thiruvarangan
Khan, Omar A.
Huntley, Jim J.
Luo, Shujun
Kwok, Pui-yan
Wu, Thomas D.
Schroth, Gary P.
Oksenberg, Jorge R.
Hauser, Stephen L.
Kingsmore, Stephen F.
author_facet Baranzini, Sergio E.
Mudge, Joann
van Velkinburgh, Jennifer C.
Khankhanian, Pouya
Khrebtukova, Irina
Miller, Neil A.
Zhang, Lu
Farmer, Andrew D.
Bell, Callum J.
Kim, Ryan W.
May, Gregory D.
Woodward, Jimmy E.
Caillier, Stacy J.
McElroy, Joseph P.
Gomez, Refujia
Pando, Marcelo J.
Clendenen, Leonda E.
Ganusova, Elena E.
Schilkey, Faye D.
Ramaraj, Thiruvarangan
Khan, Omar A.
Huntley, Jim J.
Luo, Shujun
Kwok, Pui-yan
Wu, Thomas D.
Schroth, Gary P.
Oksenberg, Jorge R.
Hauser, Stephen L.
Kingsmore, Stephen F.
author_sort Baranzini, Sergio E.
collection PubMed
description 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 pathogenesis(1,2,3,4,5,6,7,8). However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture(9,10,11,12). 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature08990) contains supplementary material, which is available to authorized users.
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spelling pubmed-28625932010-10-29 Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis Baranzini, Sergio E. Mudge, Joann van Velkinburgh, Jennifer C. Khankhanian, Pouya Khrebtukova, Irina Miller, Neil A. Zhang, Lu Farmer, Andrew D. Bell, Callum J. Kim, Ryan W. May, Gregory D. Woodward, Jimmy E. Caillier, Stacy J. McElroy, Joseph P. Gomez, Refujia Pando, Marcelo J. Clendenen, Leonda E. Ganusova, Elena E. Schilkey, Faye D. Ramaraj, Thiruvarangan Khan, Omar A. Huntley, Jim J. Luo, Shujun Kwok, Pui-yan Wu, Thomas D. Schroth, Gary P. Oksenberg, Jorge R. Hauser, Stephen L. Kingsmore, Stephen F. Nature Article 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 pathogenesis(1,2,3,4,5,6,7,8). However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture(9,10,11,12). 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature08990) contains supplementary material, which is available to authorized users. Nature Publishing Group UK 2010-04-01 2010 /pmc/articles/PMC2862593/ /pubmed/20428171 http://dx.doi.org/10.1038/nature08990 Text en © The Author(s) 2010 This article is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits distribution, and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation, and derivative works must be licensed under the same or similar licence.
spellingShingle Article
Baranzini, Sergio E.
Mudge, Joann
van Velkinburgh, Jennifer C.
Khankhanian, Pouya
Khrebtukova, Irina
Miller, Neil A.
Zhang, Lu
Farmer, Andrew D.
Bell, Callum J.
Kim, Ryan W.
May, Gregory D.
Woodward, Jimmy E.
Caillier, Stacy J.
McElroy, Joseph P.
Gomez, Refujia
Pando, Marcelo J.
Clendenen, Leonda E.
Ganusova, Elena E.
Schilkey, Faye D.
Ramaraj, Thiruvarangan
Khan, Omar A.
Huntley, Jim J.
Luo, Shujun
Kwok, Pui-yan
Wu, Thomas D.
Schroth, Gary P.
Oksenberg, Jorge R.
Hauser, Stephen L.
Kingsmore, Stephen F.
Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
title Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
title_full Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
title_fullStr Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
title_full_unstemmed Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
title_short Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
title_sort genome, epigenome and rna sequences of monozygotic twins discordant for multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862593/
https://www.ncbi.nlm.nih.gov/pubmed/20428171
http://dx.doi.org/10.1038/nature08990
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