Continuing the discussion about heredity from where we left off…

Inheritance is not always as straightforward as a simple interaction of one dominant and one recessive allele for each trait. In this post, I‘ll cover the concept of co-dominance and what happens where there is more than one allele for a trait.

Perhaps the simplest explanation of this concept comes from the example of our blood types. In the early 20^th century Karl Landsteiner and several other investigators independently discovered the ABO blood type distinctions. The problem was that following accidents involving significant blood loss, patients required transfusions of red blood cells (RBCs) in order for them to supply the body with significant oxygen and to drain it of excess carbon dioxide. Curiously, some transfusions worked, while others failed with fatal consequences.

The key was that some transfusions worked. If they all failed, then we would just assume that RBCs can’t be moved from one person to another. So there was a pattern that needed to be deciphered.

We know now that the ABO antigens are the result of enzymes which ‘decorate’ a specific protein, the H antigen, found on these cells. All RBCs have the H antigen, but it gets modified by an enzyme during its synthesis. This enzyme attaches –or decorates – carbohydrate molecules to the H antigen in specific ways. One form of this enzyme decorates the antigen in one way (producing the ‘A’ antigen), one form decorates it in another way (producing the ‘B’ antigen) and one form makes a non-functional enzyme that doesn’t attach any carbohydrate at all (the ‘O’ antigen).

RBCs with antigens on surface

What do these proteins and carbohydrates have to do with blood transfusions? Understanding this requires a simple understanding of the immune system. This system is in place to keep the body safe and free from pathogens (and cancer). It operates primarily by discriminating between two groups:

Self – Cells and cell products of the individual are effectively invisible to that individual’s own immune system (this is a simplification, but it will suffice here)

Non-Self – anything that is not recognized as self will be attacked by the immune system. Non-self consists of foreign particles, micro-organisms and even cancer cells (these are considered ‘altered-self’)

Because of the way the immune system operates, people with type A blood will not react to the ‘A antigen’, but will react to the ‘B antigen’. People with type B blood will not react to the ‘B antigen’, but will react to the ‘A antigen’. People with blood type O will have immune reactions against both A and B antigens. However, because type O blood does not have any unique antigen, no one’s immune system will react to it.

These immune attacks can be very severe if the body is infused with a significant amount of mismatched blood leading to a systemic inflammatory reaction and quite possibly death.

But back to our main focus – genetics. What does the ABO blood group have to do with inheritance? The answer is that this phenomenon is an excellent example of co-dominance and what it looks like when more than one allele occurs for a single trait.

The two antigens A and B result from the alleles I^A and I^B, respectively. These two alleles are co-dominant, which means that whenever an individual carries one of these alleles, they will express the phenotype. People who have the I^A allele have type A blood because their RBCs have the A-antigen on the surface. People who have the I^B allele have type B blood because their RBCs have the B-antigen on the surface. And People who have both the the I^A allele and the I^B allele have type AB blood because their RBCs have both the A- and B- antigens on the surface. The immune system of these people will not react to A or B antigens, and therefore can accept blood transfusions from all blood types.*

A third allele, i, is recessive to both I^A and I^B alleles because i does not encode a functional enzyme – this amounts to a null case.

One can see now how these three alleles interact with one another.  It may also be evident that  people who have type A blood may be either of ‘I^A I^A’ or I^Ai genotype.Consider a woman with blood type AB and a man with blood type O. What alleles do they carry and what blood types might their children have?

So, if a family comes into a clinic for their flu shots and it is found that mom had type AB blood, Dad has type O blood and they have three children with type A, B and type O blood, what are all five people’s probable genotypes and what is the problem?

Mom:AB

Dad: O

Child1: A

Child2: B

Child 3: O

*Again, I am over-simplifying. There is another antigen, Rh, that is also important for blood transfusions and cannot be ignored in the real world. We will get to that soon, but not in this post.