94 Hemophilia: a sex-linked disorder

Would you like to know one of the most underappreciated pieces of cytoplasm out there?

Platelets.

We take for granted the function of our platelets, which are fragments of cytoplasm that help stop us from bleeding. They help our blood to clot when we get hurt.

But there is a disorder called hemophilia that can affect those platelets and even a basic cut could be dangerous for them because they could bleed continuously.

We have many treatments for the symptoms of Hemophilia now that have greatly improved outcomes with this disorder. Although it wasn’t always that way.

Hemophilia is a sex-linked, recessive trait, which means it is different from basic Mendelian genetic problems. We still use the terms dominant and recessive for alleles – but this time – those alleles are on sex chromosomes. This is the case with sex-linked traits.

What is a sex chromosome? Recall that humans have 46 chromosomes. Chromosomes are made up of DNA and protein. They contain your genes. Well, two of your 46 chromosomes – they are called the sex chromosomes. In a karyotype, it is usually the last two chromosomes that are the sex chromosomes.

The sex chromosomes are called X and Y chromosomes but it has nothing to do with the shape of the chromosome. That’s kind of confusing but please don’t think that Y chromosomes are shaped like a Y and X chromosomes are shaped like a X. That used to always confuse me – that has nothing to do with their name. The reason they got those names is actually kind of interesting so to the Google for that. Everyone has a X chromosome. But if you have another X chromosome – meaning you have two X chromosomes – you are female. And if you have a Y chromosome – meaning you have a X and Y chromosome – you are male.

There are also genetic disorders where you can have extra copies of sex chromosomes but we are not going into that for this clip.

Sex-linked traits are traits that are specifically on the sex chromosomes. Most sex-linked traits tend to be on the X chromosome, because it is larger than the Y chromosome and contains more genes than the Y chromosome. The disorder hemophilia is like this.

We will use the letter “H” to represent an allele for not having hemophilia and a letter “h” to represent an allele for having hemophilia. Hemophilia is a recessive disorder, which is why it is being represented by a lowercase letter h. Only, it must be placed on the sex chromosomes as a superscript. Like an exponent.

Let me explain what I mean by that. A woman that does not have hemophilia could have the genotype X^HX^H or X^HX^h.

Because as long as she’s got at least one dominant allele – that dominating allele – will be what shows. So no hemophilia, since again, hemophilia is a recessive disorder. The only way for her to have hemophilia would be the genotype X^hX^h. Because only when there is no dominant present will that recessive show up, at least in this type of trait.

For a male to not have hemophilia, his genotype would have to be X^HY. Notice how I didn’t put anything on the Y chromosome – again, most sex linked traits are on the X chromosome. If he has the genotype X^hY, then he has hemophilia. He doesn’t have two X chromosomes, so in this disorder, he either has it or he doesn’t. There is no heterozygous genotype for the male so he cannot be a carrier.

So let’s say two people that do not have hemophilia have children. However, let’s say the woman is a carrier. That means she is heterozygous.

How do you do a sex-linked Punnett square cross for this kind of trait?

Step 1) Identify the genotypes of the parents. So the mother is X^HX^h. She doesn’t have hemophilia because of the dominant allele present but she is a carrier. The male, if he does not have hemophilia, must be X^HY. There’s no other option for him.

Step 2) Place one parent on the top, outside of the square like this. Place the other parent on the left, outside of the square, like this.

Step 3) Cross them!

For formatting purposes, place X chromosomes before Y. You also write any sex chromosomes with dominant letters first.

The results you get in the squares would be the offspring – the babies.

The genotype ratio could be written out like this.

The phenotype ratio – remember that these are the traits – can be written out that there is a 75% chance that a child will be born without hemophilia and a 25% chance that a child would have hemophilia, for this boy here.

Notice that in this type of example of a sex linked recessive disorder – boys are more likely to inherit this disorder – because they only have one X chromosome. This is true for many other sex linked recessive disorders, such as color blindness.

Well that’s it for the Amoeba Sisters and we remind you to stay curious!

The X chromosome is one of two sex chromosomes. Humans and most mammals have two sex chromosomes, the X and Y. Females have two X chromosomes in their cells, while males have X and Y chromosomes in their cells. Egg cells all contain an X chromosome, while sperm cells contain an X or a Y chromosome. This arrangement means that during fertilization, it is the male that determines the sex of the offspring.

A diagram shows X-linked recessive inheritance. In the first panel, the male parent is shaded purple and there is a mutation marked on his X chromosome and no mutation marked on his Y chromosome. The female parent is gray and has no mutations marked on either X chromosome. These two parents could produce four possible children. The first is a son who inherited an unmutated X chromosome from the female parent and the unmutated Y chromosome from the male parent. The second is a daughter who is a carrier and is shaded half purple. She inherited an unmutated X chromosome from the female parent and the mutated X chromosome from the male parent. The third is a son who inherited an unmutated X chromosome from the female parent and the unmutated Y chromosome from the male parent. The fourth is a daughter who is a carrier and is shaded half purple. She inherited an unmutated X chromosome from the female parent and the mutated X  chromosome from the male parent.

In the second panel, the male parent is shaded gray and there are no mutations marked on either the X or the Y chromosome. The female parent is a carrier and is shaded half purple. She has a mutation marked on one of her X chromosomes. These two parents could produce four possible children. The first is a son who is shaded purple because he is affected. He inherited a mutated X chromosome from the female parent and the unmutated Y chromosome from the male parent. The second is a daughter who is a carrier and is shaded half purple. She inherited a mutated X chromosome from the female parent and an unmutated X chromosome from the male parent. The third is a son who is unaffected because he inherited an unmutated X chromosome from the female parent and the unmutated Y chromosome from the male parent. The fourth is a daughter who is unaffected because she inherited the unmutated X chromosome from the female parent and an unmutated X  chromosome from the male parent.

A Punnett square is shown illustrating a cross between a carrier female (X^HX^h) and a normal male (X^HY). Above each column is a circle representing an egg. One egg is labeled X^H (X big H) and the second is labeled X^h (X little h). Next to each row are circles with tails representing sperm. One sperm is labeled X^H (X big H) and the second is labeled with a Y for the Y chromosome which does not contain the H gene. The first offspring has the genotype X^HX^H. The second has the genotype X^HX^h. The third has the genotype X^HY. The fourth is surrounded by a red box and has the genotype X^hY.