<p>Monozygotic (MZ) twins have been widely employed for dissection of the relative contributions of genetics and environment in disease.   In multiple sclerosis (MS), an autoimmune demyelinating disease that commonly causes neurodegeneration and disability in young adults,   disease discordance in MZ twins has been interpreted to indicate environmental importance in pathogenesis. However, genetic and epigenetic   differences between MZ twins have been described, challenging the accepted experimental paradigm in disambiguating effects of nature and   nurture.  Here, we report the genome sequences of one MS-discordant MZ twin pair and messenger RNA (mRNA) transcriptome and epigenome   sequences of CD4+ lymphocytes from three MS-discordant, MZ 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 (indels). 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 indel genotypes, or expression of ~19,000 genes in CD4+ T cells. Only two to 176 differences   in methylation of ~2 million CpG sites were detected between siblings of the three twin pairs, in contrast to ~800 differences in   methylation between T cells of unrelated individuals and several thousand differences between tissues or normal and cancerous tissues.   In the first systematic effort to estimate sequence variation among MZ co-twins, we did not find evidence for genetic, epigenetic or   transcriptome differences that explained disease discordance. These are the first female, twin and autoimmune disease genome sequences   reported.</p>

Genome, Epigenome and RNA Sequences of MZ Twins Discordant for MS

Description

Applying For Access

Summary