Phenotypic differences in genetically identical organisms: the epigenetic perspective

Abstract

Human monozygotic twins and other genetically identical organisms are almost always strikingly similar in appearance, yet they are often discordant for important phenotypes including complex diseases. Such variation among organisms with virtually identical chromosomal DNA sequences has largely been attributed to the effects of environment. Environmental factors can have a strong effect on some phenotypes, but evidence from both animal and human experiments suggests that the impact of environment has been overstated and that our views on the causes of phenotypic differences in genetically identical organisms require revision. New theoretical and experimental opportunities arise if epigenetic factors are considered as part of the molecular control of phenotype. Epigenetic mechanisms may explain paradoxical findings in twin and inbred animal studies when phenotypic differences occur in the absence of observable environmental differences and also when environmental differences do not significantly increase the degree of phenotypic variation.

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

“…It may be more realistic to regard them as the tip of an iceberg, overlying a mass of genetic/epigenetic/phenotypic/ environmental discordance that pervades MZ twinning in general. In fact, these epigenetic/genetic events may be more potent in phenotypic discordance than the supposed ''environmental'' influences that have previously been thought to drive the phenotypes of MZ (and DZ) twins apart [Singh et al, 2002a;Wong et al, 2005] (Fig. 1).…”

A epigenética como nova hipótese etiológica no campo psiquiátrico contemporâneo

“…Ao mesmo tempo em que outros mecanismos genéticos e moleculares começam a ser explorados, os estudos epidemiológicos mantêm a busca pelos fatores ambientais que influenciam o surgimento das patologias mentais, mas adotando a mesma suposição da etiologia complexa que surge da interação gene-ambiente (JABLONKA, 2004;WONG;PETRONIS, 2005;OS;RUTTEN;POULTON, 2008;OH;PETRONIS, 2008;FOLEY et al, 2009;RUTTEN;MILL, 2009;DICK;RILEY;KENDLER, 2010). Também no caso da pesquisa epidemiológica, a hipótese epigenética parece solucionar antigos problemas e questões não resolvidas e pode, inclusive, redirecionar os objetivos e as características das investigações na área.…”

“…Uma das principais suposições das pesquisas epidemiológicas residia na diferença de ocorrência de transtornos 775 mentais entre gêmeos monozigóticos: se os indivíduos possuem a mesma carga genética, as diferenças de ocorrência dos transtornos poderiam ser atribuídas à exposição a fatores ambientais não partilhados pelos irmãos. A pesquisa com gêmeos monozigóticos criados em ambientes distintos era uma das principais estratégias de pesquisa epidemiológica para identificar os fatores ambientais que conduziriam às doenças (WONG; PETRONIS, 2005;OS;RUTTEN;POULTON, 2008;OH;PETRONIS, 2008).…”

Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

“…Methylation of genomic DNA may affect a variety of processes related to gene expression, such as Xinactivation, imprinting, or expression of specific genes . Since DNA modification is a dynamic process, it is only partially stable and there is a great potential for epigenetic variation within MZ twin pairs [Wong et al, 2005].…”