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Proceedings of the National Academy of... Jul 2005Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as... (Comparative Study)
Comparative Study
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.
Topics: 5-Methylcytosine; Acetylation; Adult; Analysis of Variance; DNA Methylation; Electrophoresis, Capillary; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Histones; 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; X Chromosome Inactivation
PubMed: 16009939
DOI: 10.1073/pnas.0500398102 -
Methods (San Diego, Calif.) Jun 2016As a final function of various epigenetic mechanisms, chromatin regulation is a transcription control process that especially demonstrates active interaction with... (Review)
Review
As a final function of various epigenetic mechanisms, chromatin regulation is a transcription control process that especially demonstrates active interaction with genetic elements. Thus, chromatin structure has become a principal focus in recent genomics researches that strive to characterize regulatory functions of DNA variants related to diseases or other traits. Although researchers have been focusing on DNA methylation when studying monozygotic (MZ) twins, a great model in epigenetics research, interactions between genetics and epigenetics in chromatin level are expected to be an imperative research trend in the future. In this review, we discuss how the genome, epigenome, and transcriptome of MZ twins can be studied in an integrative manner from this perspective.
Topics: Epigenesis, Genetic; Epigenomics; Genome, Human; Humans; Phenotype; Transcriptome; Twins, Monozygotic
PubMed: 26548893
DOI: 10.1016/j.ymeth.2015.10.020 -
Journal of Assisted Reproduction and... Oct 2022The risk of monozygotic twins (MZTs) is increased in couples undergoing assisted reproductive technology (ART) treatments. Several systematic reviews have investigated...
PURPOSE
The risk of monozygotic twins (MZTs) is increased in couples undergoing assisted reproductive technology (ART) treatments. Several systematic reviews have investigated the possible determinants linked to ART, but results obtained have not been conclusive. The study aims to investigate whether the incidence of MZT differed among ART centers.
METHODS
This is a multicenter retrospective cohort study using the Italian ART National Registry database and involving the centers reporting data from individual ART cycles from 2015 to 2019. To investigate the incidence of MZT, only single embryo transfer cycles were considered. Women who had sex-discordant deliveries were excluded. MZT rate was calculated as the number of multiple pregnancies (more than one gestational sac at first ultrasound) out of the total number of clinical pregnancies. A binomial distribution model was used to determine the 95% CI of the frequency of MZT.
RESULTS
Eighteen centers were included, and they provided data on 10,433 pregnancies. The total number of MZT was 162, corresponding to an incidence of 1.5% (95% CI: 1.3-1.8%). The rate of MZT among centers varied between 0% (95% CI: 0.0-25.9%) and 3.2% (95% CI: 1.3-8.1%). All the 95% CIs included 1.5%, rejecting the hypothesis that the MZT rate may significantly differ among centers.
CONCLUSIONS
The rate of MZT did not significantly vary among ART centers. Local factors are unlikely to explain the increased rate of MZT in ART pregnancies.
Topics: Pregnancy; Female; Humans; Twinning, Monozygotic; Twins, Monozygotic; Embryo Transfer; Retrospective Studies; Reproductive Techniques, Assisted; Pregnancy, Twin
PubMed: 36053372
DOI: 10.1007/s10815-022-02603-z -
American Journal of Medical Genetics Jan 1996The use of the adjective "identical" rather than monozygotic leads to misunderstandings about the biology of monozygotic twinning. Most monozygotic twin pairs are not... (Review)
Review
The use of the adjective "identical" rather than monozygotic leads to misunderstandings about the biology of monozygotic twinning. Most monozygotic twin pairs are not identical; there may be major discordance for birth weight, genetic disease, and congenital anomalies. These indicate that postzygotic events may lead to the formation of two or more cell clones in the inner cell mass and early embryo that actually stimulate the monozygotic twinning event. There is also evidence that there may be unequal allocation of numbers of cells to the monozygotic twins; this may have widespread implications for the cascade of developmental events during embryogenesis, formation, and vascularization of the placenta. Large-scale zygosity testing at birth could be the template for analysis of twin outcomes and their biologic causes.
Topics: Chorion; DNA; Dosage Compensation, Genetic; Embryonic and Fetal Development; Female; Genetic Variation; Genotype; Humans; Male; Models, Genetic; Mosaicism; Mutation; Phenotype; Placenta; Pregnancy; Twins, Monozygotic; Zygote
PubMed: 8741866
DOI: 10.1002/(SICI)1096-8628(19960122)61:3<216::AID-AJMG5>3.0.CO;2-S -
Genome Biology Jan 2018Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities...
BACKGROUND
Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity.
RESULTS
Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This "epigenetic supersimilarity" apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer.
CONCLUSIONS
These results establish a link between early embryonic epigenetic development and adult disease. More broadly, epigenetic supersimilarity is a previously unrecognized phenomenon that may contribute to the phenotypic similarity of monozygotic twins.
Topics: CpG Islands; DNA; DNA Methylation; Epigenesis, Genetic; Genome, Human; Humans; Models, Genetic; Neoplasms; Twins, Dizygotic; Twins, Monozygotic
PubMed: 29310692
DOI: 10.1186/s13059-017-1374-0 -
American Journal of Medical Genetics.... May 2009Monozygotic twins (MZ) are rarely absolutely "identical." This review discusses the types of genetic/epigenetic and prenatal environmental post-zygotic mechanisms that... (Review)
Review
Monozygotic twins (MZ) are rarely absolutely "identical." This review discusses the types of genetic/epigenetic and prenatal environmental post-zygotic mechanisms that cause discordance within such twin pairs. Some of these mechanisms--ranging from heterokaryotypia to skewed X-chromosome inactivation--may cause extreme discordance, but these extremes are merely the more emphatic examples of discordance that, to some degree, underlies the majority of MZ twin pairs. Because of the entrenched misconception that MZ twins are necessarily identical, many MZ twin pairs are mistakenly designated as dizygotic (DZ). Clinical benefits to accurate zygosity determination include correct solid organ transplantation matching, if one twin requires donation for a non-genetically mediated disease; the opportunity of preventive management for disorders that do not manifest synchronously; and better counseling to parents regarding their individually unique, and often psychologically puzzling, twin offspring. In twin pairs with complex and confusing biological origins, more detailed zygosity testing may be required. For example, intermediate trigametic and tetragametic chimeric dizygotic twins are reviewed, some of whom are, nevertheless, monochorionic (MC). Because of inter-fetal vascular anastomoses in MC twins, genetic results from blood samples may not accurately reflect discordance in solid organs. Previously, it was thought that MZ twinning was some sort of embryological fluke. However, familial monozygotic twinning is more common than suggested by the literature. Seven new families are presented in an accompanying paper. Despite the difficulties and dangers of twin pregnancy (especially so for MC twins), human twinning persists, and continues to both challenge and fascinate parents, clinicians and geneticists.
Topics: Chimera; Humans; Teratogens; Twins, Dizygotic; Twins, Monozygotic
PubMed: 19363805
DOI: 10.1002/ajmg.c.30212 -
American Journal of Medical Genetics.... Mar 2023
Topics: Humans; Male; Diseases in Twins; Twins, Dizygotic; Twins, Monozygotic
PubMed: 36775950
DOI: 10.1002/ajmg.a.62796 -
Journal of Biological Rhythms Feb 2013Twin studies have highlighted that a large proportion of variability in chronotype is accounted for by individual-specific environmental factors (non-shared...
Twin studies have highlighted that a large proportion of variability in chronotype is accounted for by individual-specific environmental factors (non-shared environmental influences). However, little research has aimed to identify specific non-shared environmental influences on chronotype. Although epidemiological studies have shed light on possible environmental influences on chronotype, a substantial amount of research has highlighted the importance of genetic influences on exposure toward specific environments, a process termed gene-environment correlation. It is possible that associations between the environment and chronotype are in part determined by genetics, rather than being purely environmental in origin. One way of exploring the contribution of purely non-shared environmental components on associations between chronotype and the environment is to use the monozygotic twin differences design. This design allows us to tease apart the influences of genetics and the environment to identify purely environmental components. One hundred eighty-nine monozygotic twin pairs (mean age 19.81 years, SD = 1.26, range = 18-22 years, 66.1% female) completed the Horne and Östberg Morningness-Eveningness Questionnaire as a measure of chronotype and questionnaires assessing the following candidate non-shared environmental influences: dependent and independent negative life events, educational attainment, employment status, relationship status, deviant peers, affiliation with deviant peers, general health, smoking, drug use, and alcohol use. Linear regression analyses indicated the presence of gene-environment correlation for the majority of associations between chronotype and candidate environmental influences. When controlling for genetic and shared environmental effects, within monozygotic twin-pair differences in chronotype were associated with within monozygotic twin-pair differences in dependent negative life events (β = -0.27, p < 0.001), educational attainment (β = -0.14, p < 0.05), smoking status (β = 0.22, p < 0.01), and drug use (β = -0.16, p < 0.01). These results suggest that some of the association between these variables is purely environmental in nature. The associations between the remaining environmental variables and chronotype, however, may be intertwined with underlying genetic factors. These findings add to our understanding of genetic and environmental mechanisms underlying the biological clock.
Topics: Adolescent; Adult; Circadian Clocks; Circadian Rhythm; Environment; Female; Humans; Male; Surveys and Questionnaires; Twins, Monozygotic; Young Adult
PubMed: 23382591
DOI: 10.1177/0748730412468698 -
BMC Medicine Aug 2012Genetic-epidemiological studies on monozygotic (MZ) twins have been used for decades to tease out the relative contributions of genes and the environment to a trait.... (Review)
Review
Genetic-epidemiological studies on monozygotic (MZ) twins have been used for decades to tease out the relative contributions of genes and the environment to a trait. Phenotypic discordance in MZ twins has traditionally been ascribed to non-shared environmental factors acting after birth, however recent data indicate that this explanation is far too simple. In this paper, we review other reasons for discordance, including differences in the in utero environment, genetic mosaicism, and stochastic factors, focusing particularly on epigenetic discordance. Epigenetic differences are gaining increasing recognition. Although it is clear that in specific cases epigenetic alterations provide a causal factor in disease etiology, the overall significance of epigenetics in twin discordance remains unclear. It is also challenging to determine the causality and relative contributions of environmental, genetic, and stochastic factors to epigenetic variability. Epigenomic profiling studies have recently shed more light on the dynamics of temporal methylation change and methylome heritability, yet have not given a definite answer regarding their relevance to disease, because of limitations in establishing causality. Here, we explore the subject of epigenetics as another component in human phenotypic variability and its links to disease focusing particularly on evidence from MZ twin studies.
Topics: DNA Methylation; Diseases in Twins; Epigenesis, Genetic; Fetus; Gene-Environment Interaction; Humans; Stochastic Processes; Twins, Monozygotic
PubMed: 22898292
DOI: 10.1186/1741-7015-10-93 -
Developmental Science Nov 2018School performance is one of the most stable and heritable psychological characteristics. Notwithstanding, monozygotic twins (MZ), who have identical genotypes, differ...
School performance is one of the most stable and heritable psychological characteristics. Notwithstanding, monozygotic twins (MZ), who have identical genotypes, differ in school performance. These MZ differences result from non-shared environments that do not contribute to the similarity within twin pairs. Because to date few non-shared environmental factors have been reliably associated with MZ differences in school performance, they are thought to be idiosyncratic and due to chance, suggesting that the effect of non-shared environments on MZ differences are age- and trait-specific. In a sample of 2768 MZ twin pairs, we found first that MZ differences in school performance were moderately stable from age 12 through 16, with differences at the ages 12 and 14 accounting for 20% of the variance in MZ differences at age 16. Second, MZ differences in school performance correlated positively with MZ differences across 16 learning-related variables, including measures of intelligence, personality and school attitudes, with the twin who scored higher on one also scoring higher on the other measures. Finally, MZ differences in the 16 learning-related variables accounted for 22% of the variance in MZ differences in school performance at age 16. These findings suggest that, unlike for other psychological domains, non-shared environmental factors affect school performance in systematic ways that have long-term and generalist influence. Our findings should motivate the search for non-shared environmental factors responsible for the stable and systematic effects on children's differences in school performance. A video abstract of this article can be viewed at: https://youtu.be/0bw2Fl_HGq0.
Topics: Academic Performance; Adolescent; Attitude; Child; Gene-Environment Interaction; Humans; Individuality; Intelligence; Personality; Twins, Monozygotic
PubMed: 29920866
DOI: 10.1111/desc.12694