Teaching genetics by its modern history

The BBC started up a scientific Top Gear last week – Dara Ó Briain’s ‘Science Club’ is a magazine show that is trying to present science in an accessible, friendly and fun manner. Happily for us here at Nowgen, their first show focused on genetics! So plenty for us to watch and enjoy – not least the way that genetics is (nearly) always introduced.

As is ever the case when talking about genetics, they started, or quickly focused on good old Mr Mendel; the Austrian monk who first put forward the idea of heritable units, which subsequently came to be known as genes. Mendel, correctly, identified that genes are discrete – they do not blend together as they pass through generations, like Darwin thought (silly Darwin). But Mendel incorrectly thought that genes have a simple dominant or recessive relationship. Genes are inherited in pairs, one from each parent, and we often inherit a different version of each gene (variants) from our parents. Mendel thought that only one of the gene variants (the dominant one) exerted its effect on an organism and that the only time you could see the effect of the recessive variant was if both copies of the gene were the recessive one. We now realise that it is rarely that simple.

School students up and down the land should be able to recite these Mendelian laws of inheritance, using so-called monogenic or Mendelian conditions as examples; typically cystic fibrosis (CF; caused by a recessive variant of the CFTR gene) and Huntington disease (HD; caused by a dominant variant of the huntingtin gene).

Cartoon of Mendel serving dinner, with the caption 'We grow tired of peas Brother Mendel'The problem with this approach is that it ends up leading to the language of ‘a gene for X; a gene for Y’, with X and Y being some characteristic, like height or eye colour. In reality, genes just don’t work like that. When genetics is taught through monogenic conditions like CF and HD the inevitable conclusion is that people affected by these conditions have a gene for CF or HD. Actually, we all have the CFTR gene and the huntingtin gene, but in HD and CF the genes (one or both copies) are changed from their usual form, and in their changed state they ultimately cause disease.

So how do genes work then? Genes contain instructions to make other chemicals, usually proteins. But not all genes encode proteins; many genes provide instructions to make RNA as the final product. This RNA then plays an important role in regulating the activity of other genes. Ultimately, gene products form vast networks of activity – tens or hundreds of RNAs and proteins working together to complete tasks in the cell. It’s a complicating, but fascinating area of biology!

It’s very difficult to consider a single gene in isolation and from that gene predict a phenotype (physical characteristic) with 100% accuracy. For example, changes in the BRCA1 gene lead to an increased risk of developing breast cancer. For women in the UK, on average there is a 1 in 8 lifetime risk of developing breast cancer. However, inheriting just one changed version of the BRCA1 gene (remember, two copies of each gene, one from each parent) can increase a woman’s lifetime risk of breast cancer to 80%. But other genes and her environment also play an important role, which cannot be discounted.

In our ideal world, we’d like to see genetics focus on the sequence of DNA – its alphabet of A, T, C and G that spells out these genetic instructions. It’s the variations in these letters that make us all different. The genetics that the vast majority of us experience is not based on single genes, but rather on the interactions between many genes and the environment. Let’s focus on that, not Mendel (sorry Gregor).

Images from the BBC and Bob Ridge