Identifying the Gene that Establishes a Baby's Gender

An international team of researchers identified the genetic switch that sets up a baby's gender, and that is also linked to so-called 'intersex' families.

Harry Ostrer, MD, director of the Human Genetics Program at NYU Langone Medical Center, led the team that found this gene, which is actually very important because, under normal circumstances, it allows the biological program for the development of gender to go according to plan, but if the gene mutates, it causes a glitch in the program.

What normally establishes the gender of the fetus, is the Y chromosome, and males have one X and one Y chromosome, while females have two X chromosomes.

The problem is that in some families, a child can be born with an X and a Y chromosome and develop as a female, while her brothers and male cousins can have underdeveloped or uncertain genital organs.

Dr. Ostrer, who is also a professor of pediatrics, pathology and medicine at NYU Langone Medical Center, says that they “have discovered a new molecular switch that seems to modulate the pathways between male and female development.

“It is reassuring to patients and their families to know that this happened for a reason,” he adds.

Two families – one in France and the other in New Zealand, as well as several other individuals, reported disorders of sex determination, so the Doctor worked with collaborators in England, Australia and France, for the past nine years, looking for the responsible gene.

When they finally found it, they observed that the gene, called MAP3K1, is not the first to be associated with sex determination, and it can be found in unrelated individuals.

Twenty years ago, on the Y chromosome, researchers discovered the so-called SRY male gene, and ever since, other such genes have been identified, but Dr Ostrer said that MAP3K1 may hold the key to understanding how these various genes are connected.”

In France, the researchers even used a screening test for the switch, to identify affected fetuses, children, and adults who also face a high risk of developing certain types of cancer.

There are nearly 1 in 1,000 individuals affected by these disorders, reminded Dr. Ostrer, so to have a better understanding of the prevalence of this gene, and to be able to identify new genes and pathways, he is setting up a national consortium to sequence the genomes of affected individuals and their parents.

The researchers describe their findings in the American Journal of Human Genetics, published by Cell Press.