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Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome

Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different p...

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Autores principales: Kunio, Miyake, Yang, Chunshu, Minakuchi, Yohei, Ohori, Kenta, Soutome, Masaki, Hirasawa, Takae, Kazuki, Yasuhiro, Adachi, Noboru, Suzuki, Seiko, Itoh, Masayuki, Goto, Yu-ichi, Andoh, Tomoko, Kurosawa, Hiroshi, Akamatsu, Wado, Ohyama, Manabu, Okano, Hideyuki, Oshimura, Mitsuo, Sasaki, Masayuki, Toyoda, Atsushi, Kubota, Takeo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689680/
https://www.ncbi.nlm.nih.gov/pubmed/23805272
http://dx.doi.org/10.1371/journal.pone.0066729
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author Kunio, Miyake
Yang, Chunshu
Minakuchi, Yohei
Ohori, Kenta
Soutome, Masaki
Hirasawa, Takae
Kazuki, Yasuhiro
Adachi, Noboru
Suzuki, Seiko
Itoh, Masayuki
Goto, Yu-ichi
Andoh, Tomoko
Kurosawa, Hiroshi
Akamatsu, Wado
Ohyama, Manabu
Okano, Hideyuki
Oshimura, Mitsuo
Sasaki, Masayuki
Toyoda, Atsushi
Kubota, Takeo
author_facet Kunio, Miyake
Yang, Chunshu
Minakuchi, Yohei
Ohori, Kenta
Soutome, Masaki
Hirasawa, Takae
Kazuki, Yasuhiro
Adachi, Noboru
Suzuki, Seiko
Itoh, Masayuki
Goto, Yu-ichi
Andoh, Tomoko
Kurosawa, Hiroshi
Akamatsu, Wado
Ohyama, Manabu
Okano, Hideyuki
Oshimura, Mitsuo
Sasaki, Masayuki
Toyoda, Atsushi
Kubota, Takeo
author_sort Kunio, Miyake
collection PubMed
description Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins.
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spelling pubmed-36896802013-06-26 Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome Kunio, Miyake Yang, Chunshu Minakuchi, Yohei Ohori, Kenta Soutome, Masaki Hirasawa, Takae Kazuki, Yasuhiro Adachi, Noboru Suzuki, Seiko Itoh, Masayuki Goto, Yu-ichi Andoh, Tomoko Kurosawa, Hiroshi Akamatsu, Wado Ohyama, Manabu Okano, Hideyuki Oshimura, Mitsuo Sasaki, Masayuki Toyoda, Atsushi Kubota, Takeo PLoS One Research Article Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins. Public Library of Science 2013-06-21 /pmc/articles/PMC3689680/ /pubmed/23805272 http://dx.doi.org/10.1371/journal.pone.0066729 Text en © 2013 Miyake et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kunio, Miyake
Yang, Chunshu
Minakuchi, Yohei
Ohori, Kenta
Soutome, Masaki
Hirasawa, Takae
Kazuki, Yasuhiro
Adachi, Noboru
Suzuki, Seiko
Itoh, Masayuki
Goto, Yu-ichi
Andoh, Tomoko
Kurosawa, Hiroshi
Akamatsu, Wado
Ohyama, Manabu
Okano, Hideyuki
Oshimura, Mitsuo
Sasaki, Masayuki
Toyoda, Atsushi
Kubota, Takeo
Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome
title Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome
title_full Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome
title_fullStr Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome
title_full_unstemmed Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome
title_short Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome
title_sort comparison of genomic and epigenomic expression in monozygotic twins discordant for rett syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689680/
https://www.ncbi.nlm.nih.gov/pubmed/23805272
http://dx.doi.org/10.1371/journal.pone.0066729
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