Blood Types

What is the Bombay blood group?

- A curious adult from the US

July 13, 2018

Perhaps you have heard of the “blood type gene”. The blood type gene can come in three different versions: A, B or O. The versions you inherit determine whether your blood is type A, type B, type AB, or type O.

Appropriately, the blood type gene is named ABO. When we talk about the genetics of blood type, we typically only refer to the ABO gene. And that’s okay. Usually we don’t need to go into greater detail.

Bombay blood group is different. Everyone in this group tests as having type O blood, no matter what their ABO genes are. Imagine someone with the A version and the B version of ABO. They should have type AB blood. But if they are in the Bombay blood group, they will still test as type O.

That’s because there are actually multiple genes that affect blood type. ABO is not the only one. Bombay blood group is caused by one of the other genes. So let’s delve a little deeper into the genetics of blood type!

An Order of Operations

For many genes, we say one version of the gene is “dominant” to another version. This is fairly common in genetics. In fact, it happens with the ABO gene, where A and B are both dominant to O.

But some traits aren’t as simple. Often, multiple genes affect the same trait. One way this might occur is when the genes act in a sequence with each other.

When one gene requires another to act before it, it is called epistasis. We say that the first gene to act in a sequence is epistatic to the second gene. In this relationship, the first gene to act controls the trait.



Gene 1 is epistatic to Gene 2



One example of epistasis is baldness. Baldness is epistatic to hair color. If you get the gene for baldness, it does not matter what gene you get for hair color. You will be bald.

This is where Bombay blood group comes in. People in the Bombay blood group have a broken version of a gene that is epistatic to ABO. That gene is FUT1. 

FUT1 comes in two versions, “H” and “h”. Most people have at least one copy of the “H” version of FUT1. This “H” version of FUT1 does not interfere with the ABO gene. If you have the “H” version, you’ll have whatever blood type your ABO gene says.

One working “H” version of FUT1 is enough to allow ABO to do its job. But if you have two broken “h” versions, the ABO gene no longer sets your blood type. 

People in the Bombay blood group have two copies of the broken “h” version of FUT1. Their broken “h” versions prevent ABO from affecting their blood type. No matter what their ABO gene says, they always have type O blood.

A matter of inheritance

It’s worth noting that the Bombay blood group is quite rare. It was only first discovered in Bombay (now Mumbai) in 1952. It affects one person out of 10,000 in India. It is a bit more common in Taiwan, where it affects one person in 8,000. 

It’s even rarer in other parts of the world! Among people of European ancestry, Bombay blood group is literally a one in a million event.

But as rare as it might be, it does happen. And when it happens, it can result in unexpected patterns of inheritance.

Let’s imagine one such case. Let’s pretend mom is in the Bombay blood group. She has two A versions of the ABO gene. ABO says she “should” have type A blood. But since she is in the Bombay blood group, she has two broken “h” versions of FUT1. This means ABO can’t do its job and she has type O blood.

Since Bombay blood group is rare, dad almost certainly has two working “H” versions of the FUT1 gene. Let’s also say his ABO gene has an O version and B version. He will have type B blood.

All their children will get one working “H” version of FUT1 from dad, and one broken “h” version from mom. Since ABO only needs one working “H” version, the children’s blood types will be determined by their ABO gene.

Based on mom and dad’s blood types (O and B), they would expect their children to have either type B or type O blood. But because mom has two A versions of the ABO gene, she’ll pass the A version to her children. This couple could have children with type A or type AB blood, which would seem to have come from nowhere!

But, it turns out that these results were possible after all. All it took was epistasis and the Bombay blood group.

A Protein Team

Let’s look at what happens with Bombay blood group at the molecular level.

In genetics, we like to talk about which versions of a gene produce which traits. But when we do this, we are skipping a few steps. Genes don’t produce traits directly. Instead, each gene helps make a specific protein. Then, those proteins do things in the cells of our body. The overall effect of those proteins is what we call our trait.

Our blood type trait is the result of several genes working together, including ABO and FUT1. The proteins made by these genes decorate your red blood cells with chains of sugars. 

The protein made by the ABO blood type gene attaches the last sugar to this chain. If you get the A version of the ABO gene, the protein attaches one kind of sugar. If you get the B version of the gene, it attaches a different sugar. The O version of the ABO gene doesn’t attach any sugar at all!



Your red blood cells are decorated with chains of sugars. ABO adds the last sugar to the chain. Different versions of ABO add different sugars, which determines your blood type.



So now you know what blood type really means! It is based on the identity of the last sugar in a chain that hangs off of your red blood cells.

This is where Bombay blood group comes in.

The FUT1 gene makes the second-to-last protein to act on the sugar chain. Remember that FUT1 has a working “H” version and a broken “h” version. The protein made by the “H” version properly puts a sugar on the chain. The protein made by the “h” version does not attach the sugar to the chain.



The “H” version of FUT1 adds a sugar to the chain. The “h” version does not.


 

The versions of FUT1 are called “H” and “h” for a reason. When the “H” version of FUT1 attaches a sugar to the chain, the chain is called the “H antigen”. When the broken “h” version of FUT1 fails to attach a sugar to the chain, the H antigen is not formed.

The “H” version of FUT1 is dominant to the “h” version. If you get one working “H” version of FUT1, it is enough to do all the work. The blood cells all get the H antigen.

So what does this have to do with blood type? The protein from the ABO gene adds its sugar on to the H antigen. The A version of ABO changes the “H antigen” to the “A antigen”. The B version of ABO changes the “H antigen” to the “B antigen”. The O version doesn’t change anything. People with type O blood have the H antigen hanging from their red blood cells!



The H antigen is changed to the A antigen or B antigen by the A or B version of ABO. The O version of ABO leaves the H antigen unchanged.



People in the Bombay blood group have two broken “h” versions of FUT1. As a result, they can’t make the H antigen.

The protein made by ABO will only attach its sugar to the H antigen. So if you are in the Bombay blood group, and you don’t have any H antigen, your versions of ABO do not matter. Without the H antigen around, none of them will be able to do their job.



If you only have broken “h” versions of FUT1, you won’t make any H antigen. Since the ABO protein acts on the H antigen, it can’t find a place to do its job.



So why do people in the Bombay blood group test as type O? I mentioned that type O blood features the H antigen. But people in the Bombay blood group don’t make the H antigen. What’s the deal?

The answer has to do with how we test for blood type. People in the Bombay blood group don’t have the H antigen. They also don’t have the A antigen or B antigen.

Blood tests don’t look for the H antigen. They are only looking for A and B. Someone who doesn’t have A or B is assumed to be normal type O. So, the blood test simply can’t tell the difference between type O blood and the Bombay blood group.
 


By Robert Coukos, 
Stanford University 

More Information

An O parent with Bombay blood can have an AB child

Other unusual blood types can also lead to children with unexpected blood types, including Cis-ABChimerism, and Rare mutations

People in the Bombay blood group must receive blood from other people in the Bombay blood group. They often have to find donors internationally.

Selected References
Dean. Blood Groups and Red Cell Antigens: The ABO blood group.
Dean. Blood Groups and Red Cell Antigens: The Hh blood group.
 


If one parent is in the Bombay blood group, their children may have unexpected blood types.
Image modified from Pixabay


Bombay blood group is very rare. It affects one person out of 10,000 in India, though it is a bit more common in Taiwan
Image from Wikimedia


The Bombay blood group looks O in a blood test.
Image from Wikimedia