Medical researchers have made a discovery which describes why some babies have disorders of sex development. The study was conducted at the University of Melbourne. The study proposes that a critical regulatory gene on the Y chromosome increases or decreases the activity of a specific gene. This gene will determine whether a baby will be male or female.
The study, ‘Human Sex Reversal is caused by Duplication or Deletion of Core Enhancers Upstream of SOX9,’ was published in the journal Nature Communications. MCRI scientist and Hudson Institute Ph.D. scholar, Brittany Croft, was the first author.
“The chromosome make-up at conception determines the sex of a baby. An embryo with two X chromosomes results in a girl, whereas an embryo with an X-Y combination will become a boy,” Croft said.
Croft states that critical gene is called as SRY. It makes another gene called SOX9 which initiate the development of testes. High SOX9 concentrations are required for normal male development.
“But, if there is any disruption in the activity of SOX9. And low levels are present, a testis will not develop. Thus resulting in a baby with a disorder of sex development.”
Lead author, Professor Andrew Sinclair, speaks that “junk DNA” which is also called as “dark matter” forms 90% of human DNA. Instead of carrying genes, it contains regulatory DNA segments called enhancers which increase or decrease gene activity.
“If these enhancers are disrupted it may lead to a baby being born with an abnormal sex development.”
The purpose of the present study was to explore how enhancers regulate SOX9. And whether their disturbance would cause disorder of sex development.
Sinclair says the team found three enhancers which ensure SOX9 is triggered to a high level in an XY embryo, leading to normal testis and normal male development.
“Significantly, we recognized XX patients who would generally have ovaries and be female but carried extra copies of enhancers, (high levels of SOX9) and instead developed testes. Furthermore, XY patients who had lost SOX9 enhancers, (low levels of SOX9) and developed ovaries rather than testes.”
Croft explains this sex reversal. He said it is caused by gain or loss of the critical enhancers which regulate SOX9. This shows how vital they are for normal development of the male.
This study is important because in the past scientists have only observed genes for the diagnosis of these patients. But we have exposed that you need to look outside the genes to the enhancers. Professor Sinclair said that there were around 1 million enhancers across the human genome controlling about 22,000 genes.
“These are the enhancers which lie on the DNA but outside genes. These enhancers may contain the key to diagnosing many disorders which hide in the poorly understood dark matter of DNA.”
Professor Andrew Sinclair, Lead Author