Medical researchers at Melbourne's Murdoch Children's Research Institute have discovered how a baby's sex is determined and it's not just about the XY chromosomes , but involves a 'regulator' that increases or decreases the gene activity which decides if we are male or female.

The study, 'Human Sex Reversal is caused by Duplication or Deletion of Core Enhancers Upstream of SOX9' has been published in the journal Nature Communications. MCRI researcher and Hudson Institute Ph.D. student, Brittany Croft, is the first author. "The sex of a baby is determined by its chromosome make-up at conception. An embryo with two X chromosomes will become a girl, while an embryo with an XY combination results in a boy," Ms. Croft said.

X Chromosome

"The Y chromosome carries a critical gene, called SRY, which acts on another gene called SOX9 to start the development of tests in the embryo.

"However, if there is some disruption to SOX9 activity and only low levels are present, a testis will not develop resulting in a baby with a disorder of sex development." Lead author of the study, Professor Andrew Sinclair, said that 90 percent of DNA is made up of so-called 'junk DNA or dark matter' which contains no genes but does carry important regulators that increase or decrease gene activity.

"These regulatory segments of DNA are called enhancers," he said. If these enhancers that control testis genes are disrupted, it may lead to a baby being born with a disorder of sex development. " Professor Sinclair, who is also a member of the Paediatrics Department of the University of Melbourne, said this study sought to understand how the SOX9 gene was regulated by enhancers and if disruption of the enhancers would result in disorders of sex development.

SOX9 gene

"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," he 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 tests.

Besides, we found XY patients who had lost these SOX9 enhancers, (low levels of SOX9) and developed ovaries instead of testes. " Ms. Croft said that human sex reversal is in these cases. that regulate the SOX9 gene; consequently, these three enhancers are required for normal tests and male development. "

"This study is significant because the patients have only looked at genes to diagnose these patients, but we have shown that you need to look outside the genes to the enhancers," Ms. Croft said.