Inherited Epigenetic Traits
Twin Studies Reveal a New Form of Inheritance in Methylation
Jan 20, 2009 Alicia Mae Prater
Epigenetics is a relatively new field of genetics that studies chemical alterations on chromosomes, which result in changes in gene expression by condensing the chromosome or affecting the binding of transcription factors. Methylation of CpG islands is one such alteration. Twin studies have opened the doors to understanding how these changes occur: They’re inherited.
Epigenetic Methylation Patterns
DNA methyltransferase is an enzyme in cells that recognizes CpG islands, strings of cytosines and guanines, and attaches a methyl group to cytosine. This DNA methylation is absent during embryonic development due to the high level of replication and gene expression. The alteration is thought to condense the chromatin around histones, closing off access to the DNA for transcription factors as gene expression wanes and is shut off. In fact, altered methylation patterns are thought to play a role in the development of some cancers, which result from aberrant cellular programming.
The Importance of Twin Studies
Twins have been used in research as a way of determining the effects of genes on disease and revealing patterns of inheritance due to the unique circumstances of their birth, resulting in similar genetic composition. Identical twins are monozygotic, the result of the fertilized egg splitting into two embryos in the womb. Fraternal twins are less identical genetically because they began as different eggs; in studies they are considered the same as siblings, who have also been used to a great extent to study the affect of genes on disease.
Since the early 1990s, the scientific literature has seen studies begin to appear regarding the disproportionate occurrence of disease in identical twins, something that was not completely explained by genetics alone and leads to questions about how identical monozygotic twins actually are.
Understanding Methylation and Epigenetic Inheritance
By comparing the methylation pattern similarities in identical twins compared to fraternal twins, Petronis’ group (Kaminsky et al.) at the University of Toronto found that there were more similarities in the methylation patterns of the identical twin pairs. The researchers also found that the methylation pattern was inherited differently from the actual gene sequence, which was more similar in the twin pairs for the loci studied (approximately 1-2% of the whole genome), meaning there are two forms of inherited material – the nucleotide sequence and the methylation pattern on the chromosomes made of that sequence.
This is by no means the first study into the patterns of epigenetic inheritance; Singh, Murphy, and O’Reilly wrote a review in 2002 assessing then recent monozygotic twin studies that indicated a more potentially complex and dynamic inheritance mechanism. The more recent work concentrated on isolating the difference between the gene sequence and the epigenetic pattern, which would have a wide reaching affect on inherited forms of disease. Epigenetics is a complexity not taken into consideration until recent years and may complicate preventative therapy, prognosis, and treatment.
References:
Kaminsky et al. DNA methylation profiles in monozygotic and dizygotic twins. Nature Genetics, 2009 (epub ahead of print).
Singh, Murphy, and O’Reilly. Epigenetic contributors to the discordance of monozygotic twins. Clinical Genetics, 62, 2002.
DNA Split for Replication
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