>>It’s generally understood that the biological sex of an embryo is determined by the chromosomes at conception – two X chromosomes will develop as female, while an XY combo will become male. But this simple rule may be too simple. A new genetics study out of Australia has identified extra pieces of the puzzle that could explain some disorders of sex development (DSD).<<

https://newatlas.com/biological-sex-junk-dna/57691/

I read it on Reddit this morning that someone’s son was diagnosed as having XXYY syndrome. I had to google it and it’s very interesting.

PermeateFree said:

>>It’s generally understood that the biological sex of an embryo is determined by the chromosomes at conception – two X chromosomes will develop as female, while an XY combo will become male. But this simple rule may be too simple. A new genetics study out of Australia has identified extra pieces of the puzzle that could explain some disorders of sex development (DSD).<<

https://newatlas.com/biological-sex-junk-dna/57691/

Interesting article.

“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,” says Andrew Sinclair, lead author of the study. “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. In addition, we found XY patients who had lost these SOX9 enhancers, (low levels of SOX9) and developed ovaries instead of testes.”

Back in the mid 1980s I was reading up about all things cytogenetics. ie. about all sorts of chromosomal disorders. Together with unusual cases like XXXXY + XXXXXXY mosaicism, there were cases of XX males and XY females that at the time were unexplained. It’s nice to see an explanation here.

What part of “junk DNA” do they mean by “enhancers”. eg. do they mean pseudogenes, STRs, what? Looking at the Nature article.

They mean DNA “within the 2 Mb upstream of the transcriptional start site” which presumably affects binding of transcription factors?

“Once Sox9 expression begins, SOX9 auto-regulates its own transcription, creating a positive feedback loop”. OK, so testes development is due to a run-away positive feedback chemical reaction.

“When combined, all three enhancers show synergistic activity, significantly increasing their individual enhancer activity.”

How?

“In vivo, deletion of these three enhancers in mice resulted in different outcomes ranging from: no apparent effect to reduced Sox9 transcription and complete sex reversal.”

Murphy’s law of biology.