Scientists have found a section of non-coding DNA that determines which genitals mice develop.
The section is called enhancer 13 (Enh13), and after the scientists deleted it in male embryos, the mice developed ovaries and female genitals instead of testes.
'For the first time we've demonstrated sex reversal after changing a non-coding region of DNA,' said Professor Robin Lovell-Badge at the Francis Crick Institute in London. 'We think Enh13 is probably relevant to human disorders of sex development and could potentially be used to help diagnose some of these cases.'
Males typically have X and Y chromosomes, while females have two sets of the X chromosome. However, around one in 5500 babies are born with incomplete or indeterminate genitals, or sex organs that do not appear to match their chromosomal sex. Many of these conditions are associated with reduced fertility.
'For decades, researchers have looked for genes that cause disorders of sex development but we haven't been able to find the genetic cause for over half of them. Our latest study suggests that many answers could lie in the non-coding regions, which we will now investigate further,' said lead author Dr Nitzan Gonen at the Francis Crick Institute.
Only 2 percent of the human genome comprises genes that produce proteins, while the other 98 percent contains non-coding DNA, once thought to be unnecessary junk DNA.
Mammal embryos develop as females unless a gene on the Y chromosome called Sry – sex-determining region Y – turns on another gene called sox9 to produce sufficient amounts of the protein SOX9 in their early development. This protein causes the sex organs to become testes, which then steer the embryo to become male. The newly discovered section, Enh13, boosts the signal from the Sry gene, producing testes.
Professor Lovell-Badge, who first identified the Sry gene 27 years ago, told the Independent: 'Sry is there and it starts the process, then you immediately get all these mechanisms that reinforce it, like enhancer 13.'
'This is pinpointing a region that was a needle in a haystack,' Professor Vincent Harley of the Hudson Institute of Medical Research in Australia, who was not involved in the study, told Science magazine.
'As we learn more we may be able to develop ways to modulate gene activity to solve a wide range of clinical problems and not just those affecting testis or ovary development,' Professor Lovell-Badge told The Guardian.
The study was published in Science.