“The simple idea of a single gene leading to a single disease is more likely to be an exception than a rule.”

Finding the Disease-Causing Genes

Things would be, not simple, but much simpler, if one gene caused one disease, and if that one disease presented itself the same way across all patients. While there are conditions that support the former part of this statement they are few and far between. Hemophilia and cystic fibrosis (CF) are two of the rare conditions caused by a single gene variant, but both of these patient populations have a wide array of presentations of disease. Not to mention the fact that some of the individuals that carry the specific disease-causing gene mutation do not contract the disease at all. These individuals are thought to carry an additional mutation that protects them, but the phenomenon is still quite a mystery.

What causes these mutations or combinations thereof? The first thing we think of is genetic diversity between humans, but environmental factors can also play a role. These include upbringing, diet, and geographic location. With so many “what ifs” how do we even begin to dissect what causes disease?

While we know that we need to investigate how genes interact with each other on a deeper level, we aren’t able to do this by just looking at individual genome sequences.

The Broad Institute estimates that to identify which specific genes cause one disease, a million human genomes would need to be examined (half a million patients and half a million healthy controls). Especially for rare diseases, this feat is practically impossible. The patient population just simply doesn’t exist.

Why it Matters

Personalized medicine is becoming more of a reality as gene therapy research continues to advance. But, in order for this approach to be successful for a wide array of illnesses, researchers need to stop thinking about genes in isolation.

“Specific combinations (of genes) may not only profoundly affect disease susceptibility, but they will likely dictate new personalized therapies.”

CRISPR technology is helping researchers understand more of these gene combinations. With the technology they’re able to turn off certain genes to help reveal the function of others. Once we know exactly which combinations of genes cause a disease like cancer, we can further delve into the investigation of certain drugs that will kill the sick cells and leave the healthy cells unharmed.

This precise killing of diseased cells would also mean less side effects for patients than traditional treatments like chemotherapy.

It’s an exciting prospect for those living with rare conditions with a high unmet need. Especially because this investigation could reveal why certain treatments might work better for a certain individual than another.

You can read more about the study of gene combinations here.