If it wasn't for mutations, we'd all still be bacteria, and my ability to type this would be severely hampered by my lack of appendages.
The GJB2 gene is the part of our DNA that creates the Connexin 26 protein. That's more or less what DNA is used for - instruction code for creating proteins. So how did my son ended up with a mutated version? Where did this mutation originate?
There's different versions of all the genes we have, which is why we are all different - for example, there are genes for blue eyes, brown eyes, grey eyes, also blonde hair, red hair, black hair, etc. Pretty much all of our physical characteristics are determined by genes, though environmental impacts have a role too, such as malnutrition, lack of exercise etc. As such there's no such thing as 'normal' and 'abnormal' genes - who decides what a 'normal' eye colour is? (some, such as Adolf Hitler, have tried). Geneticists refer to the more common functioning genes as 'wild' type, and the less common, possibly non-functional genes as mutants.
We inherit two versions of all of our genes, one from each parent. I have one 'wild' type GJB2 gene, and one with a specific mutation called c.35delG, which probably came from my mother. So does my wife. The c.35delG mutation is 'recessive'. That means you need two copies of it for it to have a notable impact. The single 'wild' GJB2 gene I have can create enough Cx26 for my hearing to work - though I could probably do with a bit more. So I carry the deafness-causing mutation, but I'm not actually deaf.
So where did this c.35delG mutation originate? There are over 300 different variations of the GJB2 gene, and most of these are considered mutations. Some are more common among Asians, some among Caucasians, some among specific Jewish populations. The c.35delG is one of the most common causes of deafness among Caucasians (such as my family), but isn't seen much in other ethnic groups. Around 1 in 50 white people carry it.
There are two reasons the mutation could be so common. The first is the 'hot-spot' theory. This proposes that the structure of the GJB2 gene has a weakness that means it keeps breaking the same way, like the ways zips always break on cheap trousers. But this wouldn't explain why it's only common among white people. If it kept breaking like that, wouldn't it be common among Africans and Asians too?
A more likely cause is what's known as the 'founder effect'. It basically says that all people carrying the mutation have a common ancestor - a single great-great-great....-great grandparent who somehow got a mutated copy of GJB2, had loads of kids and passed it on. Some geneticists think they know who here he or she was - or rather where they lived. Ancient Greece of all places, around 10,000 years ago. I think that's about 400 generations ago.
So if you have a c.35delG mutation, we are most likely related! Just like me and my wife. Though I guess everyone is related really when you think about it.
I knew very little about genetics when I started digging into this stuff. It's really fascinating, I found this book to be really good and accessible - The Gene: An Intimate History by Siddhartha Mukherjee. It's very accessible, I recommend a read of it if you have any interest.
Terminology
I'm going to start building a glossary in these blogs. I had to look up a lot of words when reading this stuff so I might save some of you the bother.
- Heterozygous This means you have one copy of a particular gene. Both me and my wife are heterozygous for the c.35delG mutation.
- Homozygous This means you have two copies of a particular gene. My son is homozygous for the c.35delG mutation
- Genotype The particular type of gene you have. My sons' genotype would be 35delG/35delG for the GJB2 gene
- Phenotype Your characteristic that are caused by a particular genotype. One phenotype of the 35delG/35delG mutated GJB2 genes is typically deafness
- Allele A particular form of a gene. The 35delG mutation is an allele of the GJB2 gene.[I often write gene where I should have written allele, mainly because most people don't know what an allele is.]
