While it is known that the sex of a baby is determined by its chromosome make-up at conception, new research has identified a “regulator” that increases or decreases the activity of genes which decide if we become male or female.
“These regulatory segments of DNA are called enhancers,” said lead author of the study Andrew Sinclair, Professor at University of Melbourne in Australia.
“If these enhancers that control testis genes are disrupted it may lead to a baby being born with a disorder of sex development,” Sinclair said.
While an embryo with two X chromosomes will become a girl, an embryo with an X-Y combination results in a boy. But the Y chromosome carries a critical gene, called SRY, which acts on another gene called SOX9 to start the development of testes in the embryo, explained Brittany Croft from Murdoch Children’s Research Institute in Melbourne.
“High levels of the SOX9 gene are needed for normal testis development,” Croft added.
This study, published in the journal, ‘Nature Communications,’ sought to understand how the SOX9 gene was regulated by enhancers and whether disruption of the enhancers would result in disorders of sex development.
“We discovered three enhancers that, together ensure the SOX9 gene is turned on to a high level in an XY embryo, leading to normal testis and male development,” Sinclair said.
“Importantly, we identified XX patients who would normally have ovaries and be female but carried extra copies of these enhancers, (high levels of SOX9) and instead developed testes,” Sinclair said.
“In addition, we found XY patients who had lost these SOX9 enhancers, (low levels of SOX9) and developed ovaries instead of testes,” Sinclair added.
Croft said human sex reversal such as seen in these cases is caused by gain or loss of these vital enhancers that regulate the SOX9 gene.