Oct 10, 2021 2 mins, 6 secs
The phenomenon, known as transgenerational epigenetic inheritance, caught the public imagination, in part because it seemed to release us from the tyranny of DNA.

A decade on, the case for transgenerational epigenetic inheritance in humans has crumbled.

One well documented finding alone seems to present a towering obstacle to it: except in very rare genetic disorders, all epigenetic marks are erased from the genetic material of a human egg and sperm soon after their nuclei fuse during fertilisation.

“The [epigenetic] patterns are established anew in each generation,” says geneticist Bernhard Horsthemke of the University of Duisburg-Essen in Germany.

In the past decade, the threads have become even more tangled, because it turns out that epigenetic marks are themselves largely under genetic control.

Some genes influence the degree to which other genes are annotated – and this shows up in twin studies, where certain epigenetic patterns have been found to be more similar in identical twins that in non-identical ones.

This has led researchers to think of the epigenome less as the language in which the environment commands the genes, and more as a way in which the genes adjust themselves to respond better to an unpredictable environment.

All the aforementioned researchers rue the fact that transgenerational epigenetic inheritance is still what most people think of when they hear the word epigenetics, because the past decade has also seen exciting advances in the field, in terms of the light it has shed on human health and disease.

While Bird and others argue that the epigenome is predominantly under genetic control, some researchers are interested in the trace that certain environmental insults leave there.

Meanwhile, the US-based company Grail – which has just been bought, controversially, by DNA sequencing giant Illumina – has come up with a test for more than 50 cancers that detects altered methylation patterns in DNA circulating freely in the blood.

Science has only scratched the surface of the epigenome, says Flanagan.

Until recently, sequencing the epigenome was a relatively slow and expensive affair.

The US firm Illumina, which leads the global DNA sequencing market, offers a different technique, and chemist Shankar Balasubramanian of the University of Cambridge has said that his company, Cambridge Epigenetix, will soon announce its own epigenetic sequencing technology – one that could add a sixth letter in the form of hydroxymethyl tags

That’s why Ewan Birney who co-directs the European Bioinformatics Institute in Hinxton, Cambridgeshire, and who is a consultant to Oxford Nanopore, says that epigenetic sequencing stands poised to revolutionise science: “We’re opening up an entirely new world.”


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