Why hemophilia is lethal (in almost 100%) for homozygotic females, while it's not lethal for hemizygotic males?

 

Both, homozygotic females and hemizygotic males don't have any healthy allel.

 

Thank you for replies

At what stage of development does the lethality usually occur in females?

Edited April 19, 20178 yr by Daecon

In prenatal stage, as I heard.

How often does anyone find out?
As far as I can see you would need a haemophiliac father and a carrier mother.

That's a fairly rare combination.

Also, until fairly recently, there was a good chance that the "father" didn't survive until adulthood.

I know it is very rare situation.

But what is the genetic reason of lethality of XhXh?

If mutation changes life-important gene at X chromosome, then XhY- should also be lethal. But it isn't. Many males live quite normally, and some of them even don't know they are sick.

 

It's easy to understand why some mutations on X chromosome are lethal for males and aren't for females. Females have second X chromosome where healthy gene exists. This rescues females lives in many recesive X-linked diseases.

 

But hemophilia is also recesive X-linked disease and situation is opposite. It's often not lethal for hemizygotic males (XhY-), where there is no chance for healthy gene, because there is no second X chromosome. It's lethal for homozygotic females (XhXh), where there is also no chance for healthy gene.

 

Why it is like that?

I guess the Y chromosome is dominant and so overpowers any haemophilia effect on the X chromosome?

The gene is on X chromosome, not on Y chromosome, so it can't be the reason.

Here's a report on an adult female who was homozygous for hemophilia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385172/. She suffered from the condition as expected, but it was not lethal.

And here's the abstract of another report of a homozygous adult female who had the condition but for whom it was not lethal: https://www.karger.com/Article/PDF/208614.

IIRC, there are about 13 factors for clotting to occur perfectly.  Heterozygotic males, namely XhY, have little  Factor VIII or IX but DO have platelets to aid clotting .  So, if I am correct, some clotting still occurs although it is imperfect. 

Edited September 17, 20178 yr by jimmydasaint