A Conversation with Dr Bryndis Yngvadottir

In this blog, we talk to Dr Bryndis Yngvadottir, a Research Associate in Medical Genetics at the University of Cambridge. 

Tell us a bit about yourself, where do you work and what do you do?

I am a Research Associate in the Department of Medical Genetics at the University of Cambridge, working with Professor Eamonn R Maher and Professor Stefan J Marciniak. My background is in human evolutionary genetics and genomics but in recent years I have focused on finding damaging genetic alterations (mutations) in genes that may lead to cancer and rare conditions, such as Birt-Hogg-Dubé syndrome.

Tell us about your experience at the Genomics England Research Summit. What was the poster you presented, and what did you learn/gain from the event?

The Research Summit was a fantastic gathering of people introducing the latest research and technology from Genomics England and beyond. I was particularly inspired by the NHS Genomic Medicine Service and their commitment to making whole genome sequencing a part of routine care to allow for early detection and treatment of genetic disorders. There were also important discussions on the underrepresentation of ethnic minorities in most large genomic studies and a desire to address this imbalance. As for my research, at the Summit I presented my team’s findings of genetic alterations in the FLCN gene, based on participants in the 100,000 Genomes Project. Our presentation received a lot of interest from attendees, some of which had never heard of Birt-Hogg-Dubé. 

Can you tell us a bit about the aims of your current research project?

Our starting point for the project was to estimate how common Birt-Hogg-Dubé syndrome is in the general population. It is generally believed to affect 1 in 200,000 people, but we suspected that this rare disorder was much more common than that. As most families with Birt-Hogg-Dubé have damaging genetic alterations in the FLCN gene, we can use their frequency to say something about the incidence of the syndrome. We did this by looking for genetic alterations in FLCN in over 500,000 genomes from participants in the 100,000 Genomes Project, the UK Biobank and Genes & Health. Our preliminary results from these datasets indicate that the frequency of damaging FLCN genetic alterations is indeed considerably higher than previous clinical estimates of Birt-Hogg-Dubé.

What large genomics studies have you been/are you involved in during your career?

Throughout the years, there have been great technological advances in DNA sequencing. Gradually it has become easier and cheaper to sequence larger parts of our genome in a greater number of individuals (from a few hundred to a few hundred thousand). At the very beginning of my career, I looked at tiny parts of our genome: mtDNA, which is inherited through females, and the Y chromosome, which is inherited through males. The focus of my research there was to learn about the population history of Icelanders. Some years later I expanded my view and started looking at the whole human genome, searching for evidence of damaging genetic alterations that may actually have been advantageous for the health and survival of our species. Then most recently I moved from evolutionary genetics to medical genetics, where I now search for damaging alterations that cause conditions like kidney cancer and Birt-Hogg-Dubé.

What advantages are there for research on rare conditions utilising large genomic studies?

Genomic studies play an important role in advancing our understanding and management of rare conditions. Understanding the genetic basis of rare conditions can, for example, lead to the development of more accurate diagnostic tests which can contribute to earlier diagnosis for patients and their families. As people with Birt-Hogg-Dubé are at a higher risk of developing kidney cancer in their lifetime, an early diagnosis of the syndrome is essential to facilitate early intervention and treatment.

What do you think the future is for using these large genomic studies to study rare conditions such as BHD Syndrome?

Owing to a lack of awareness among medical professions and its variable symptoms, Birt-Hogg-Dubé has often been overlooked. Our study has found that this rare disorder may indeed be much more common than we thought. Increased knowledge of the incidence may help raise the profile of the syndrome in the wider community and help shape the provision of medical services for patients with this rare condition. In the near future, we need to address the underrepresentation of ethnic minorities in genomic studies in general as this will allow us to work towards a more comprehensive understanding of human genetics and improve the relevance and impact of genomic research on health outcomes for all populations.