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Genomes of identical twins start to diverge in the womb

11 January 2021
Appeared in BioNews 1078

Identical twins may not in fact be genetically identical at birth, according to a new study by researchers in Iceland.

Researchers found that twin-specific genetic mutations could occur while embryos were still developing inside the womb. The team were also able to pinpoint at which stage in development the mutations occurred, by searching for them in relatives of the twins. The study provides new insights into how monozygotic or 'identical' twins form from a single egg cell.

'These are exciting times that allow us to use mutations to shed light on the development of humans at these first stages,' said Dr Kári Stefánsson, joint senior author and CEO of deCODE Genetics in Reykjavik, Iceland, where the research was carried out.

The study, published in Nature Genetics, analysed DNA sequences from the germline genomes of 381 pairs of monozygotic twins. The team found that on average, twins differed by 5.2 early-development mutations, with 15 percent of twins having a significant number of genetic changes from each other. Although 38 twin pairs were genetic duplicates, in 39 pairs more than 100 genetic differences were found between twins. 

In addition, DNA from parents, spouses, and children of the twins was sequenced, which helped determine when in development the mutation occurred. For instance, if a mutation also appeared in a twin's child, that meant it was present in the twin's germ cell, which forms very early in embryo development.

In one twin pair, the cells of one individual all contained a mutation that was only found in 20 percent of their siblings' cells. This demonstrated that while one twin descended from a single cell during early development, the other was formed from a mixture of different cell lineages. Dr Stefánsson concluded that these results could allow researchers 'to begin to explore the way in which twinning happens.' 

He added that 'it looks like coincidence is an extraordinarily important factor in which cells in the inner cell mass go into making a person', suggesting zygotes may not split into twins in a symmetrical way.

Although not all genetic mutations impact phenotype, the findings challenge the theory that twin-specific differences such as disease occurrence are solely down to environmental factors. Speaking to the Guardian, geneticist Professor Jan Dumanski at Uppsala University in Sweden, who was not involved in the study, called it 'a clear and important contribution' to medical research. Psychologist Professor Nancy Segal at California State University, Fullerton, also not involved in the research, said the findings will further understanding of the influences of nature versus nurture.

'This will force scientists to refine our thinking about the influences of genetics and environment,' she said. 'Twins are very alike but it is not a perfect similarity.'

SOURCES & REFERENCES
Differences between germline genomes of monozygotic twins
Nature Genetics |  7 January 2021
Identical twins accumulate genetic differences in the womb
The Scientist |  7 January 2021
Identical twins are not so identical, study suggests
The Guardian |  8 January 2021
Monozygous but not identical
deCODE genetics |  7 January 2021
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