X-linked dominant genes affect males more than females?

[Rhino1000]

It would seem like X-linked dominant alleles would be more likely to affect females than males, because females have twice as much odds of containing an x-linked dominant gene (because they have 2 X-chromosomes, while males only have one). However, TPR says that males are more affected by these X-linked dominant alleles. Does anyone know why this might be/if this is correct?

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[quicheduty]

X-linked dominant? It shouldn't really affect one sex over the other if it's dominant, although there may or may not be some "buffer" in the female due to X-inactivation...does TPR talk about this at all?

X-linked recessive is a lot more clear so let's twist your logic: females have twice as many X chromosomes as males, so if they have one recessive allele for an X-linked recessive disease, they have another chance at nabbing a second, dominant allele to mask that recessive trait. For males, if you have one recessive allele, you express that X-linked recessive trait and that's it. So for X-linked recessive males are more affected than females just by stats.

I can't speak on X-linked dominance, though. Perhaps someone else can jump in!

 

[Rhino1000]

X-linked dominant? It shouldn't really affect one sex over the other if it's dominant, although there may or may not be some "buffer" in the female due to X-inactivation...does TPR talk about this at all?

X-linked recessive is a lot more clear so let's twist your logic: females have twice as many X chromosomes as males, so if they have one recessive allele for an X-linked recessive disease, they have another chance at nabbing a second, dominant allele to mask that recessive trait. For males, if you have one recessive allele, you express that X-linked recessive trait and that's it. So for X-linked recessive males are more affected than females just by stats.

I can't speak on X-linked dominance, though. Perhaps someone else can jump in!

See, that explanation makes a lot of sense, as you demonstrate, but there has got to be more information present in order to account for the preferential expression of X-linked dominant alleles in males versus females. I didn't see anything about X-inactivation (but then again, they didn't give any explanation for this).

 

[Seminole Girl]

There is no gender preference for x-linked dominant traits for the most part, that is one of the tell tale signs of being able to distinguish that from x-linked recessive when studying a pedigree. The exact pattern of inheritance will depend more on whether the mother of the father is the carrier of the trait. If the father alone is the carrier then we can draw out a Punnett square and it will show us that all the daughters now carry the trait (as they HAD to get his one diseased X from him), while none of the son's carry the trait (bc they got their "healthy" X from their mother). On the other end of the spectrum, If the mother alone is the carrier of the trait then there will be an even inheritance pattern, meaning that each child, regardless of sex will have a 50% chance of having the disorder. Finally if both parents are carriers, then the Punnett square will show us that 100% of daughters will have the disorder, while 50% of male offspring will have the disorder. I hope this helps!

 

[mcloaf]

The missing link in this thread is the distinction between being affected more frequently vs more severely. X dominant phenotypes will be more severe in males, but seen more frequently in females.

 

[KGflyboy]

2 points:

1) lyonization- Every female will have halve 1/2 of her X chromosomes inactivated. Some of the mutated Xs will inactivate, and some of the wild type Xs will inactivated. The result is that the wild type gene still produces some normal protein coded by the gene controlling the X-linked disorder. Males don't have that benefit, so in some cases they show higher expressivity of the disorder.

2) Some of the genes on the inactivated X chromosomes are active despite most of the chromosome being inactive. Even if the wild type X of a heterozygous female is inactivated, there is a small chance whatever protein controls the disorder will still be produced by that chromosome, which can lessen the phenotypic impact or expressivity of the disorder caused by the mutated X chromosome.