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

BARANZINI, Sergio E ; MUDGE, Joann ; 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 ; VAN VELKINBURGH, Jennifer C ; KHAN, Omar A ; HUNTLEY, Jim J ; SHUJUN LUO ; KWOK, Pui-Yan ; WU, Thomas D ; SCHROTH, Gary P ; OKSENBERG, Jorge R ; HAULER, Stephen L ; KINGSMORE, Stephen F ; KHANKHANIAN, Pouya ; KHREBTUKOVA, Irina ; MILLER, Neil A ; LU ZHANG ; FARMER, Andrew D ; BELL, Callum J ; KIM, Ryan W

Nature (London), 2010-04, Vol.464 (7293), p.1351-1356 [Periódico revisado por pares]

London: Nature Publishing Group

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Título:
Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
Autor: BARANZINI, Sergio E ; MUDGE, Joann ; 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 ; VAN VELKINBURGH, Jennifer C ; KHAN, Omar A ; HUNTLEY, Jim J ; SHUJUN LUO ; KWOK, Pui-Yan ; WU, Thomas D ; SCHROTH, Gary P ; OKSENBERG, Jorge R ; HAULER, Stephen L ; KINGSMORE, Stephen F ; KHANKHANIAN, Pouya ; KHREBTUKOVA, Irina ; MILLER, Neil A ; LU ZHANG ; FARMER, Andrew D ; BELL, Callum J ; KIM, Ryan W
Assuntos: Adolescent ; Adult ; Allelic Imbalance - genetics ; Biological and medical sciences ; Breast - metabolism ; Breast Neoplasms - genetics ; Case-Control Studies ; CD4-Positive T-Lymphocytes - metabolism ; CpG Islands - genetics ; DNA Copy Number Variations - genetics ; DNA Methylation - genetics ; Epigenesis, Genetic - genetics ; Epigenetics ; Female ; Frequency distribution ; Genetic aspects ; Genetic Predisposition to Disease - genetics ; Genetics ; Genome, Human - genetics ; Genomes ; Genotype & phenotype ; Haplotypes - genetics ; Heterozygote ; Humans ; INDEL Mutation - genetics ; Infections ; Lung - metabolism ; Lung Neoplasms - genetics ; Lymphocytes ; Male ; Medical sciences ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Neurology ; Nucleotide sequence ; Physiological aspects ; Polymorphism, Genetic - genetics ; Quantitative Trait Loci - genetics ; Risk factors ; RNA, Messenger - analysis ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Twin studies ; Twins ; Twins, Monozygotic - genetics
É parte de: Nature (London), 2010-04, Vol.464 (7293), p.1351-1356
Descrição: 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. However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture. 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 approximately 3.6 million single nucleotide polymorphisms (SNPs) or approximately 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 approximately 19,000 genes in CD4(+) T cells. Only 2 to 176 differences in the methylation of approximately 2 million CpG dinucleotides were detected between siblings of the three twin pairs, in contrast to approximately 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.
Editor: London: Nature Publishing Group
Idioma: Inglês

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

London: Nature Publishing Group

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