Editing Epigenetics (section)

===Twins===
Direct comparisons of identical twins constitute an optimal model for interrogating [[environmental epigenetics]]. In the case of humans with different environmental exposures, monozygotic (identical) twins were epigenetically indistinguishable during their early years, while older twins had remarkable differences in the overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation.<ref name="Moore_2015"/> The twin pairs who had spent less of their lifetime together and/or had greater differences in their medical histories were those who showed the largest differences in their levels of [[5-methylcytosine]] DNA and [[acetylation]] of [[histones]] H3 and H4.<ref name="pmid16009939" />

Dizygotic (fraternal) and monozygotic (identical) twins show evidence of epigenetic influence in humans.<ref name="pmid16009939">{{cite journal | vauthors = 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 YZ, Plass C, Esteller M | title = Epigenetic differences arise during the lifetime of monozygotic twins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 30 | pages = 10604–9 | date = July 2005 | pmid = 16009939 | pmc = 1174919 | doi = 10.1073/pnas.0500398102 | bibcode = 2005PNAS..10210604F | doi-access = free }}</ref><ref name="pmid19151718">{{cite journal | vauthors = Kaminsky ZA, Tang T, Wang SC, Ptak C, Oh GH, Wong AH, Feldcamp LA, Virtanen C, Halfvarson J, Tysk C, McRae AF, Visscher PM, Montgomery GW, Gottesman II, Martin NG, Petronis A | title = DNA methylation profiles in monozygotic and dizygotic twins | journal = Nature Genetics | volume = 41 | issue = 2 | pages = 240–5 | date = February 2009 | pmid = 19151718 | doi = 10.1038/ng.286 | s2cid = 12688031 }}</ref><ref>{{cite news|title=The Claim: Identical Twins Have Identical DNA|newspaper=New York Times|url=https://www.nytimes.com/2008/03/11/health/11real.html| vauthors = O'Connor A | date=11 March 2008 | access-date=2 May 2010}}</ref> DNA sequence differences that would be abundant in a singleton-based study do not interfere with the analysis. Environmental differences can produce long-term epigenetic effects, and different developmental monozygotic twin subtypes may be different with respect to their susceptibility to be discordant from an epigenetic point of view.<ref name="pmid19653134">{{cite journal | vauthors = Ballestar E | title = Epigenetics lessons from twins: prospects for autoimmune disease | journal = Clinical Reviews in Allergy & Immunology | volume = 39 | issue = 1 | pages = 30–41 | date = August 2010 | pmid = 19653134 | doi = 10.1007/s12016-009-8168-4 | s2cid = 25040280 }}</ref>

A [[High-throughput screening|high-throughput]] study, which denotes technology that looks at extensive genetic markers, focused on epigenetic differences between monozygotic twins to compare global and locus-specific changes in [[DNA methylation]] and histone modifications in a sample of 40 monozygotic twin pairs.<ref name="pmid16009939" /> In this case, only healthy twin pairs were studied, but a wide range of ages was represented, between 3 and 74 years. One of the major conclusions from this study was that there is an age-dependent accumulation of epigenetic differences between the two siblings of twin pairs. This accumulation suggests the existence of epigenetic "drift". ''Epigenetic drift'' is the term given to epigenetic modifications as they occur as a direct function with age. While age is a known risk factor for many diseases, age-related methylation has been found to occur differentially at specific sites along the genome. Over time, this can result in measurable differences between biological and chronological age. Epigenetic changes have been found to be reflective of [[Lifestyle (social sciences)|lifestyle]] and may act as functional [[biomarker]]s of disease before clinical [[reference range|threshold]] is reached.<ref>{{cite journal | vauthors = Wallace RG, Twomey LC, Custaud MA, Moyna N, Cummins PM, Mangone M, Murphy RP | title = Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment | journal = BioMed Research International | volume = 2016 | pages = 2465763 | year = 2016 | pmid = 26942189 | pmc = 4749768 | doi = 10.1155/2016/2465763 | doi-access = free }}</ref>

A more recent study, where 114 monozygotic twins and 80 dizygotic twins were analyzed for the DNA methylation status of around 6000 unique genomic regions, concluded that epigenetic similarity at the time of blastocyst splitting may also contribute to phenotypic similarities in monozygotic co-twins. This supports the notion that [[Microenvironment (biology)|microenvironment]] at early stages of embryonic development can be quite important for the establishment of epigenetic marks.<ref name="pmid19151718"/> Congenital genetic disease is well understood and it is clear that epigenetics can play a role, for example, in the case of [[Angelman syndrome]] and [[Prader–Willi syndrome]]. These are normal genetic diseases caused by gene deletions or inactivation of the genes but are unusually common because individuals are essentially [[hemizygous]] because of [[genomic imprinting]], and therefore a single gene knock out is sufficient to cause the disease, where most cases would require both copies to be knocked out.<ref>{{OMIM|105830}}</ref>