Is Factor V Leiden a Mendelian Disorder?

Here is a great question I got from a student about the genetics of Factor V Leiden.

Q. Factor V Leiden is autosomal dominant – but it doesn’t seem to follow Mendel’s laws. Would you say it shows incomplete dominance?

A. This is such a good question! Factor V Leiden is an autosomal dominant disease – and you’re right: it does NOT follow Mendelian laws. However, the non-Mendelian pattern it follows is not incomplete dominance, but incomplete penetrance.

First, here’s why Factor V Leiden is a non-Mendelian disorder.

Factor V Leiden is an autosomal dominant disease. If it followed Mendel’s laws, everyone who inherited ether one or two copies of the Factor V Leiden gene (which is the dominant gene) would display the same phenotype (in this case, they’d all have the same exact amount of abnormal clot formation). But that’s not how it works in this disease.

Patients with factor V Leiden have an increased risk of developing abnormal clots. But not everyone with an FVL gene (or even with two FVL genes) develops a clot! Some do, and some don’t. So the phenotype is not the same in everyone with the FVL gene.

So how would you describe this non-Mendelian weirdness?

This weird phenomenon is called incomplete penetrance.

In Mendel’s experiments, his dominant alleles showed complete penetrance. In other words, every plant with a genotype containing a dominant allele (or two!) always displayed the same phenotype.

But in real life, that’s not always the case – sometimes penetrance is not complete, and factor V Leiden is a good example. As we mentioned above, the factor V Leiden gene confers an increased risk of abnormal clotting – but that’s all it is, just a risk, not a certainty. So some patients with the FVL gene display the disease phenotype, and some do not.

Incomplete dominance is also a non-Mendelian pattern of gene expression – but it’s different than incomplete penetrance.

In Mendelian dominance, there are two alleles and two phenotypes. In the left image below, the two phenotypes are purple and white flower colors – and as long as you have at least one dominant allele (in this case, P), you’ll get a purple flower.

In incomplete dominance, there are two alleles and three phenotypes. In the right image below, the phenotypes are red, white, and pink flower colors. If you are homozygous for either the R or the W allele, you’ll get a red or a white flower. But if you have both the R and the W allele, you’ll get a “blend” of the two other phenotypes – a pink flower!