Identical but not the same: The value of discordant monozygotic twins in genetic research

Abstract

Monozygotic (MZ) twins show remarkable resemblance in many aspects of behavior, health, and disease. Until recently, MZ twins were usually called "genetically identical"; however, evidence for genetic and epigenetic differences within rare MZ twin pairs has accumulated. Here, we summarize the literature on MZ twins discordant for Mendelian inherited disorders and chromosomal abnormalities. A systematic literature search for English articles on discordant MZ twin pairs was performed in Web of Science and PubMed. A total number of 2,016 publications were retrieved and reviewed and 439 reports were retained. Discordant MZ twin pairs are informative in respect to variability of phenotypic expression, pathogenetic mechanisms, epigenetics, and post-zygotic mutagenesis and may serve as a model for research on genetic defects. The analysis of single discordant MZ twin pairs may represent an elegant approach to identify genes in inherited disorders.

Causes and consequences of obesity: the contribution of recent twin studies

“…In addition to complex, continuous phenotypes such as height, weight and aspects of personality where MZ twins exhibit a high degree of similarity, MZ twins are nearly always concordant for Mendelian genetic diseases. Studying cases where MZ twins present with differences in the manifestation (onset, severity, response to treatment, and so on) of Mendelian diseases has helped to uncover disease mutations as well as broadened the clinical spectrum of diseases previously thought to be more uniform in presentation (Reviewed by Zwijnenburg et al, 2010). 1 Recently discordant MZ twins have also been utilized in the hunt for polymorphisms contributing to complex traits such as obesity.…”

“…Studying cases where MZ twins present with differences in the manifestation (onset, severity, response to treatment, and so on) of Mendelian diseases has helped to uncover disease mutations as well as broadened the clinical spectrum of diseases previously thought to be more uniform in presentation (Reviewed by Zwijnenburg et al, 2010). 1 Recently discordant MZ twins have also been utilized in the hunt for polymorphisms contributing to complex traits such as obesity. 2 Twin studies have a long history in the Finland.…”

Epigenetic Basis of Twin Discordance in Diseases: Future Benefits

“…Epigenetic modifications of chromatin and DNA have been recognized as important permissive and suppressive factors in controlling the expressed genome via gene transcription. There are four major epigenetic mechanisms within the cell which are; posttranslational modifications of histone proteins, methylation of DNA, RNA-associated silencing and genomic imprinting (4,5). Histone modifications such as methylation and acetylation are more flexible (shortterm) modifications whereas in differentiated adult cells, DNA methylation is more stable long-term modification (6).…”

An Evolutionary Biology Approach to Understanding Neurological Disorders

“…This has been due to limitations of the methodology employed, as well as other factors, such as evidence demonstrating monozygotic twins are less genetically similar than once thought (Zwijnenburg et al, 2010). A further example is that of PKD, which was long considered a non-hereditary disorder (Shulman et al, 2011;Westerlund et al, 2010).…”