1. Introduction

In the previous tutorial, we looked at the inheritance of autosomal traits in which there was one gene with two alleles and two phenotypes. For example, with cystic fibrosis, you could inherit a “C” allele, resulting in a normal phenotype, or a “c” allele, resulting in cystic fibrosis in “cc” homozygotes.  In terms of phenotypes, there were only two possibilities: either you have cystic fibrosis, or you don’t. The same is true of all of the traits that Mendel studied in his garden peas.

The inheritance of blood types — types A, B, AB, and O — is a more complex system. We’ll use it to introduce two new genetics concepts:

1. Multiple Alleles
2. Co-Dominance.

2. Gene Loci, Multiple Alleles, and Co-Dominance

On a physical level, genes are segments of DNA located on a chromosome. The specific location of a gene on a chromosome is referred to as its locus. In the last tutorial, we saw that the locus for the hemoglobin gene was near the top of chromosome 11. The gene locus for the chloride channel that malfunctions in cystic fibrosis is on chromosome 7.

The locus for the ABO blood type system is on the bottom of chromosome 9. But rather than having two alleles, the ABO blood type gene has three alleles. While any individual will only inherit two alleles (one from their mother, the other from their father) there are other people in the human population who have a third allele.

There are two widely used sets of symbols used to represent these alleles. One uses the letters A, B, and o (and that’s the one we’ll be using below). Another system found in many textbooks uses I^A, I^B, and i. 

When a gene locus has more than two alleles, it’s called multiple alleles. Note that having multiple alleles at a gene locus is not an unusual exception to the two allele systems we met in the last tutorials. Multiple allele systems are common and are a normal part of genetic variation in humans (and other eukaryotic organisms).

The three alleles at the ABO locus interact with each other as follows:

1. The A and B alleles are both dominant to the o allele. For example, if an individual inherits an A allele and an o allele, he or she will have the “A” phenotype, or Type A blood.
2. A and B are co-dominant to one another. What that means is that if an individual inherits an A allele and a B allele, they express both phenotypes, and their phenotype will be blood type “AB.” Not that this isn’t a blended phenotype (which is another type of inheritance that we’ll address below). It’s not like pouring white paint into a bucket of red paint and getting pink paint. It’s more like pouring screws into a bucket of nails. You get a bucket of screws and nails.

With these concepts in hand, let’s look at the ABO blood type system

3. The ABO Blood Type System

The ABO blood type system is based on glycoproteins— proteins attached to polysaccharides — found on the membranes of red blood cells.

• If your red blood cells have the A glycoprotein, your blood type is type A.
• If you have the B glycoprotein, you’re type B.
• If you have both glycoproteins, you’re type AB.
• If you don’t produce either glycoprotein, you’re type O.

The presence or absence of these membrane glycoproteins only matters during blood transfusions. During a transfusion, someone who has suffered blood loss receives blood from a donor. If the blood is the right type, the procedure can be life-saving. But if the donor doesn’t have the right blood type, the procedure can be fatal. Here’s how the underlying biology works.

Our immune system is how our body defends itself against disease-causing viruses, bacteria, fungi, worms, and other parasites. In relationship to blood type, the important thing to know is that the cells of the immune system are constantly surveying the molecules inside our body, and and deciding if those molecules belong to us or if they indicate the presence of an infection.

Molecules perceived as foreign are known as antigens. In response to an antigen, your immune system will counterattack with proteins called antibodies. One of the effects of antibodies is to coat invading bacteria and viruses in such a way as to keep them infecting other cells. Often these cells form clumps that are later swallowed up and disposed of by another part of the immune system — white blood cells.

In the case of the ABO blood type system, this makes some blood transfusions deadly. If you’re type O and receive blood with the A or B glycoprotein, your immune system will perceive the red blood cells carrying these glycoproteins as invaders. The subsequent clumping (called agglutination) causes shock and death.

People with blood type AB have both glycoproteins on their blood cells. As a result, any type of transfused blood (A, B, AB, or O) can be received without a reaction.

Having read that, see if you can complete the chart and answer the questions below.

4. The Genetics of ABO Blood Type

Now let’s look at the genetics of this system. At the top of this page, we described two key features involved in ABO blood type inheritance.

• Co-dominance
• Multiple Alleles.

Here’s more information about how the three alleles work.

• The A allele codes for the A glycoprotein.
• The B allele codes for the B glycoprotein.
• The o allele codes for nothing.

And since you already know about codominance, go ahead and complete the table and questions below:

4. What about blood types like A+, or O-?

Blood types are typically expressed with a “+” or a “-” sign, such as “A+”(pronounced as “A positive”) or “AB-” (pronounced as “AB negative”). These “+” and “-” designations for blood type are about an another system of genes and proteins on the surface of red blood cells. These proteins are called “Rh factors.” The “Rh” is for Rhesus Monkey, a small Asian monkey, often used in medical research, in which these factors were discovered.

In the Rh system, there are two phenotypes: Rh+ and Rh- (pronounced “Rh positive” and “Rh negative). A person who is Rh+ has the Rh protein on the surface of their red blood cells, and a person who is Rh- doesn’t produce the protein. Note that this parallels the ABO system in that people who are type A or B produce the A or B glycoprotein, while a person who is type O produces nothing.

The allele for producing an Rh protein is dominant to the allele for not producing one. Using Rh+ to represent the allele for producing the Rh protein and Rh- to represent the allele for not producing an Rh protein, complete the table and answer the questions below.

With the Rh factor, problems can arise related to an immune reaction that an Rh- woman can have towards an Rh+ fetus. Here’s how this works:

A woman who is Rh- usually has no difficulty with her 1st pregnancy (diagram 1). But during birth, there’s usually some contact between the newborn baby’s blood and the mother’s blood. That exposes the mother’s immune system to Rh+ cells (diagram 2). In response, the Rh- mother will develop antibodies and what’s called immunological memory against the Rh+ protein (shown in diagram 3).

The problem arises in the next pregnancy. If an immune-sensitized Rh- mother is carrying an Rh+ fetus (diagram 4), her immune system will create antibodies that cross the placenta and attack the fetus’s red blood cells and liver, causing harm to the fetus that can be fatal.

Effective prenatal care has reduced the incidence of Rh syndrome to a very low level in many countries. A blood test can determine the phenotypes of the parents. If an Rh- mother receives an injection either during her first pregnancy or shortly after her first birth, her immune system can be prevented from producing anti-Rh factor antibodies.

If you want to learn more about Rh disease, you can do so at the March of Dimes website or the Stanford Medicine Children’s Health Center website.

5. Solving Blood Type Problems

You solve genetics problems involving blood type in pretty much the same way as you solve any other type of problem. The same six steps I advocated in the last tutorial apply here (click on the link if you need to review).

What’s next?

Proceed to the text tutorial: Topics 5.3 – 5.5, Part 3: Solving Genetic Problems involving sex-linked alleles