Epigenetic differences arise during the lifetime of monozygotic twins

Mario F Fraga; Esteban Ballestar; Maria F Paz; Santiago Ropero; Fernando Setien; Maria L Ballestar; Damia Heine-Suñer; Juan C Cigudosa; Miguel Urioste; Javier Benitez; Manuel Boix-Chornet; Abel Sanchez-Aguilera; Charlotte Ling; Emma Carlsson; Pernille Poulsen; Allan Vaag; Zarko Stephan; Tim D Spector; Yue-Zhong Wu; Christoph Plass; Manel Esteller

doi:10.1073/pnas.0500398102

Epigenetic differences arise during the lifetime of monozygotic twins

Mario F Fraga, Esteban Ballestar, Maria F Paz, Santiago Ropero, Fernando Setien, Maria L Ballestar, Damia Heine-Suñer, Juan C Cigudosa, Miguel Urioste, Javier Benitez, Manuel Boix-Chornet, Abel Sanchez-Aguilera, Charlotte Ling, Emma Carlsson, Pernille Poulsen, Allan Vaag, Zarko Stephan, Tim D Spector, Yue-Zhong Wu, Christoph PlassManel Esteller

3047 Citations (Scopus)

Abstract

Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.

Original language	English
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	30
Pages (from-to)	10604-9
Number of pages	6
ISSN	0027-8424
DOIs	https://doi.org/10.1073/pnas.0500398102
Publication status	Published - 26 Jul 2005
Externally published	Yes

Keywords

5-Methylcytosine/metabolism
Acetylation
Adult
Analysis of Variance
DNA Methylation
Electrophoresis, Capillary
Epigenesis, Genetic/genetics
Female
Gene Expression Regulation, Developmental
Histones/metabolism
Humans
Male
Nucleic Acid Amplification Techniques
Oligonucleotide Array Sequence Analysis
Phenotype
Restriction Mapping
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Spain
Surveys and Questionnaires
Twins, Monozygotic/genetics
X Chromosome Inactivation/genetics

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10.1073/pnas.0500398102

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Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., Boix-Chornet, M., Sanchez-Aguilera, A., Ling, C., Carlsson, E., Poulsen, P., Vaag, A., Stephan, Z., Spector, T. D., Wu, Y.-Z., ... Esteller, M. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America, 102(30), 10604-9. https://doi.org/10.1073/pnas.0500398102

Fraga, MF, Ballestar, E, Paz, MF, Ropero, S, Setien, F, Ballestar, ML, Heine-Suñer, D, Cigudosa, JC, Urioste, M, Benitez, J, Boix-Chornet, M, Sanchez-Aguilera, A, Ling, C, Carlsson, E, Poulsen, P, Vaag, A, Stephan, Z, Spector, TD, Wu, Y-Z, Plass, C & Esteller, M 2005, 'Epigenetic differences arise during the lifetime of monozygotic twins', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 30, pp. 10604-9. https://doi.org/10.1073/pnas.0500398102

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abstract = "Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.",

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T1 - Epigenetic differences arise during the lifetime of monozygotic twins

AU - Fraga, Mario F

AU - Ballestar, Esteban

AU - Paz, Maria F

AU - Ropero, Santiago

AU - Setien, Fernando

AU - Ballestar, Maria L

AU - Heine-Suñer, Damia

AU - Cigudosa, Juan C

AU - Urioste, Miguel

AU - Benitez, Javier

AU - Boix-Chornet, Manuel

AU - Sanchez-Aguilera, Abel

AU - Ling, Charlotte

AU - Carlsson, Emma

AU - Poulsen, Pernille

AU - Vaag, Allan

AU - Stephan, Zarko

AU - Spector, Tim D

AU - Wu, Yue-Zhong

AU - Plass, Christoph

AU - Esteller, Manel

PY - 2005/7/26

Y1 - 2005/7/26

N2 - Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.

AB - Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.

KW - 5-Methylcytosine/metabolism

KW - Acetylation

KW - Adult

KW - Analysis of Variance

KW - DNA Methylation

KW - Electrophoresis, Capillary

KW - Epigenesis, Genetic/genetics

KW - Female

KW - Gene Expression Regulation, Developmental

KW - Histones/metabolism

KW - Humans

KW - Male

KW - Nucleic Acid Amplification Techniques

KW - Oligonucleotide Array Sequence Analysis

KW - Phenotype

KW - Restriction Mapping

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sequence Analysis, DNA

KW - Spain

KW - Surveys and Questionnaires

KW - Twins, Monozygotic/genetics

KW - X Chromosome Inactivation/genetics

UR - https://www.scopus.com/pages/publications/23044514669

U2 - 10.1073/pnas.0500398102

DO - 10.1073/pnas.0500398102

M3 - Journal article

C2 - 16009939

SN - 0027-8424

VL - 102

SP - 10604

EP - 10609

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 30

ER -

Epigenetic differences arise during the lifetime of monozygotic twins

Abstract

Keywords

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