Conversation with Gemma Marfany. Part 1

Today we’re going to talk to Gemma Marfany. She’s associate professor of Genetics at University of Barcelona -where we are right now- and she works on human molecular genetics trying to understand the genetic and molecular bases of vision diseases. In diseases which have a simple Mendelian way of transmission, mainly in retinal dystrophies; dissecting the factors that are important in the retina function with the differentiation of several neuron types. She also tests the same mutations, the same genes, in model organisms and she’s also very interested in bioethical issues derived from the use of DNA in societies and scientific dissemination.

In this interview we’re going to talk mainly on the importance of genetic of simple Mendelian traits in humans and how they are at the base of many diseases in humans, that are in general very rare. But as we’ll see, very rare, but very important for the people suffering them and this is the base of what is called clinical genetics. Gemma, why in genetics today the Mendelian traits are so important? Well, first I have to introduce a bit of genetics. So, what we are as organisms is our phenotype, that means our traits -physical and also behavioral, many different types of characteristics-, this one we call phenotype. Then, how are we? How we are?

It’s due to the genes that we have inherited from our parents but also to the environment. So, depending on the characteristic, the importance of genes is huge, and the environmental part is very small, but for some other traits the genetics part is small, tiny, and then the environmental part is big. For Mendelian traits the genetics part is huge; and for many, many characteristics of our organism, of our body, they are encoded in genes so if the sequence of the gene is correct, we are “normal”; but if there is a mutation, if there is a change in the sequence, then the protein encoded is not functional and then we have a disease.

So, by knowing the sequence of the gene -if it’s right, if it’s mutated- we can then infer if we’re going to suffer from a disease or not. In these cases, “the transmission” means “the transmission of the disease”, meaning what do you called the penetrance is very strong. That’s right. So, what I’m telling is that when we are studying Mendelian traits in humans, the thing is that if you just look at the genes, you can infer if this person is going to suffer from diseases or not. So, what we are talking about the inheritance and we say if “there is dominant or its recessive” in fact we are talking about the disease.

If the disease is going to be shown in the organism with only one copy of the genes mutated or you need two copies of the gene mutated, if it’s in all chromosomes that are not sexual or if it is in the X chromosome. So, by this, we can infer then if the person is going to be affected with the disease or not, or even if they are not affected, if they can transmit it to the progeny which is also very important for society. No doubt. If the transmission is so easy, why do you need so much molecular works to understand so much the mechanism, underlying the genetic effects to understand the disease?

I think that we should view our organism as if we are making a tridimensional piece with little pieces like with Lego, and then one of the pieces is not working. Okay, you know, this piece is not working but it’s not working alone, actually is interacting with some other pieces. So, you need to know, not only the brick that is not working but where in the whole picture you have to put the brick so to understand what is happening there Why? Because the important thing is not only to know if you’re going to suffer from the disease or not, but what is a molecular pathway, what is not working properly in your body.

If you know exactly what in the pathway is not working, then you can try first to prevent people having it, so you can make a prenatal diagnosis, or you make a diagnosis. This is the first thing, so you can advise people they’re going to have someone affected or not, you can prevent, and you can treat the disease. So, if you know exactly what is not functioning, then you can apply some type of treatment, and that’s the important thing. You’re not making it by trial-error, you’re just knowing what is not working fine and then you apply a treatment for this. So, this is the rational approach, trying to make societies more healthy.