Brand new genes from Ugandan villages

There are very few African studies in genetics - and a study in the journal Cell addresses that problem with, alongside other data, an unprecedented resource of DNA from people in rural Uganda. One of the authors,- Deepti Gurdasani, previously worked on it at the Sanger Intitute in Cambridge. But, as she tells Phil Sansom, she was one part of a big project...

Deepti - ...a collaboration with the Medical Research Council Uganda and the Uganda Virus Research Institute that has occurred over a decade. And a lot of this work was actually led by Segun Fatumo who has trained in genome wide association study analysis through this process.

Phil - Segun Fatumo is a scientist who’s originally from Nigeria who became one of the key figures here.

Segun - I came to the University of Cambridge and Sanger to do a postdoc.

Phil - Segun worked closely with Deepti to create what they now call the Ugandan Genome Resource.

Deepti - This is very much the first large-scale dataset that examines genome sequences, genetic diversity within Uganda, as well as looks at the association between genes and different clinical traits.

Phil - Where in Uganda exactly are we talking about?

Deepti - Southwestern rural Uganda. Essentially 25 villages...

Segun - So we went to the rural communities to talk with the leadership of the villages, make them understand what we are trying to do.

Phil - Were people interested? Were they keen?

Segun - Yes. I think... It's very interesting to let you kn ow that in Africa, people are very receptive to research compared to what you will see for example in the Western world.

Deepti - This is a community that was quite primed to medical research as they had participated in other studies before.

Segun - Since 1989 every year...

Deepti - And they were very keen to participate in a study that looked at risk factors for things like heart disease, diabetes, and high blood pressure. These are diseases that are becoming more and more common in different parts of Africa. Also, everyone in the study got free treatment for their high blood cholesterol or high blood pressure or things that could increase their risk for heart disease.

Phil - What did you get out in the end? How many people's genes or data did you get?

Deepti - So in the end we had data on about 6,400 individuals from this region. We had whole genome sequencing data on 2,000 individuals. This is one of the largest and most comprehensive studies that has been carried out within Africa.

Phil - Those are unprecedented numbers for genetics in Africa - thousands of whole genomes. But there are some smaller datasets from places like Egypt and South Africa that Deepti could get access to.

Deepti - We combined the data with other resources that we had access to within Africa to develop a dataset of about 14,000 individuals. And we looked at the association between different genes and a number of diseases including diabetes, high blood pressure, high cholesterol levels.

Phil - Were you surprised by what you eventually got out the other end?

Deepti - Yes. I think the biggest surprise for us was looking at the new genes we found associated with disease. And almost all of them were driven by genetic variants that were only found in African populations.

Phil - The team found a bunch of stuff - new genes and version of genes that are linked in different ways to your health. Some of this genetic variance barely exists outside of Africa. And according to Segun Fatumo, some of it straight-up doesn’t exist outside of Africa.

Segun - Genetic variance is more diverse in African populations compared to other populations.

Phil - It's where we all came from, isn't it.

Segun - Yeah, that's exactly it. So that's where we all came from. So what that means is that there are some variations that you will find in African population that you would never find elsewhere.

Phil - In some of these cases it feels like if the only dogs you’d ever seen before were chihuahuas, and you assumed they were all tiny and fluffy, then one day you saw a great dane. Both Deepti and Segun told me about one gene variant in particular.

Deepti - One that particularly stands out was an association we found between a particular genetic variant that causes a blood disorder called alpha thalassaemia.

Segun - Alpha thalassaemia.

Deepti - It's a blood disorder that leads to anaemia, which is very common in Africans. So it's found in about 22% of Africans. And it's almost absent in European pop ulations, but in Africa, in regions where malaria is endemic, having this particular disorder can protect you from severe malaria and actually helps survival.

Phil - Really? So one disorder helps you... stops you getting another disease?

Deepti - Yes. It's really interesting. There's several blood disorders that have been diagnosed in Africans, the alpha thalassaemia variant and sickle cell anaemia, both of which protect against severe malaria. They actually help you survive. So we found that this was associated, this particular variant was associated with a marker for diabetes, which we call glycated haemoglobin. This is a marker that's used commonly to diagnose diabetes everywhere in the world, but we found that this genetic variant changed the levels of glycated haemoglobin independently of whether somebody had diabetes or not.

Phil - Glycated haemoglobin - haemoglobin is the stuff in your red blood cells that carries oxygen around the body, and glycated means it’s bonded with sugar. So it’s linked to blood sugar. It’s a really common type of health checkup, and in some ways it’s more helpful than a straight-up blood sugar test - because glycated haemoglobin gives the average blood sugar levels over the past two or three months, so you can spot long-term patterns - and hopefully, diabetes,

Phil - But here’s the rub: Deepti is saying that her alpha thalassaemia gene changes your glycated haemoglobin. That means a diabetes test is no longer a diabetes test.

Deepti - Yes, so we may be picking up people with alpha thalassaemia rather than picking up people who have or don't have diabetes.

Phil - I see. So there's actual... not only are there big differences in the genetics, there's real world implications.

Deepti - Yes, exactly. And this is what we find in African studies. African populations respond differently to drugs. They have genetic variants that cause particular markers to change. So we really have to rethink how we diagnose diseases in African populations and how they respond to drugs, et cetera. When we studied genetics specifically in these populations.