By Hasmik Baghdasaryan, program representative, The Promise Armenian Institute
In 2016, UCLA and ArmGenia Research Charitable Trust of Yerevan signed a Memorandum of Understanding (MoU) to sequence and interpret genomes on DNA samples from Armenia in hopes of gaining a better understanding of the genetic roots of the Armenian people. This collaboration was realized thanks to a generous donation from UCLA alumna and daughter of Armenian genocide survivors, Sara Chitjian.
To date, 49 DNA samples have been sequenced, interpreted and presented under the leadership of Dr. Wayne Grody and his team in the UCLA Clinical Genomics Center. In 2020, The Promise Armenian Institute at UCLA provided a seed grant to the Armenia Medical Genomics Project to continue sequencing and interpretation of 30 additional samples collected from Artsakh.*
I recently sat down with Dr. Grody, a professor in the departments of Pathology & Laboratory Medicine, Pediatrics and Human Genetics at the UCLA David Geffen School of Medicine, and Salpy Akaragian, director emeritus, UCLA Health, to talk about the project.
Is there a particular reason for the concentration on Artsakh during this phase of the research?
Akaragian: The UCLA-ArmGenia partnership started in 2016, with the initial intention of studying the genome of Armenians from the Republic of Armenia, Artsakh and Western Armenia. We looked at samples from Kharpert, Erzurum, Beyazet (cities in historic Armenia/eastern Turkey) and Artsakh. However, due to the unavailability of suitable samples from Western Armenia — from individuals with three generations of ancestry on both sides of the family — we shifted our concentration to Artsakh.
Grody: When doing genetic mapping or genetic sequencing in a population, it is advantageous to have a homogeneous population, in other words, a population that’s not mixed — as that makes the statistics too complicated. Previously, we looked at a few regions that have been by themselves for a long time; of those, we discovered that Artsakh was the most homogeneous, historically isolated and maybe even the most ancient.
Studying very ancient populations that have not interbred with others is also valuable in human genetics. For example, for genetic mapping in the U.S., we study populations like the Amish and the Mormons; however, these groups are nowhere near as ancient as the Armenians, who are likely one of the most ancient populations that survive to this day. Unfortunately, because Armenia is such a small country, it has been ignored by human geneticists up until now.
While the number of samples we are looking at, 30–50, doesn't give us the statistical power to do a historical migration study, we hope they will assist us in identifying some disease-related genetic markers that will be helpful to public health in Armenians in both the home country and the diaspora.
How will your findings be used? What are some of the potential impacts of this work?
Grody: Whereas our previous studies focused on rare and ultra-rare diseases, with this new seed grant funded by the Promise Armenian Institute, we will be looking for common adult diseases that pose serious public health issues in Armenians, such as cardiovascular disease, hypertension, and the like.
We hope to identify common recessive diseases for carrier screening in individuals of reproductive age, which is currently not being done in Armenia. While they will not be able to screen for the 200+ diseases that are screened for in the U.S. due to cost, we hope to identify some of the most frequent diseases that are worth examining.
Knowing the frequency of common diseases can inform public health measures, such as putting in place certain services, surveillance, treatments and medications to be prepared to face and address these issues. In this new phase of the study, we’re hoping to form the groundwork for personalized medicine for the Armenian population. If we can’t cure or prevent these diseases, hopefully we can at least modify them through lifestyle changes.
The next phase of the study will bring a clinical aspect to the research component, whereby a genetic counselor from the U.S. will consult with the director of the project in Armenia to implement appropriate clinical interventions when/if DNA samples reveal markers indicative of an actionable medical diagnosis that can be prevented or treated — such as breast cancer, hearing loss or familial Mediterranean fever.
Akaragian: Through clinical research findings, we know and can identify the top medical diagnosis for the population of Artsakh. However, to the best of my knowledge, no one has conducted and/or published findings of whole genome or exome sequencing and/or interpretations to validate this information.
The findings of this research can have impacts beyond public health. Having data that identifies frequent and common diseases can lead to public health policy changes, cooperation with pharmaceuticals, entrepreneurship, public education, family planning and more.
How did UCLA come to be involved in this project, and in what ways is the collaboration between UCLA and scientists from Armenia uniquely positioned to tackle this research?
Akaragian: To begin with, UCLA has the best scientists and researchers in the field of human genetics. In 2015, when Dr. Sevak Avagyan, a colleague and co-founder of the ArmGenia Research Charitable Trust, asked for an expert in the field to lead this research — because no such specialists exist in Armenia — I immediately recommended Dr. Grody. Thankfully, he showed interest and agreed to take on this project. It’s also important to note that Dr. Grody sequences and interprets the data voluntarily.
Grody: There were several reasons why this project interested me. First, our lab at UCLA is a leader in genomic medicine. We were the first center in the world to offer clinical-grade whole-exome/genome sequencing to patients with undiagnosed disorders: a test that has solved the diagnostic odyssey for many people. We are applying the same technology to the ArmGenia project.
Moreover, the fact that this project was Armenian meant a lot to me. Our diagnostic DNA lab, which I established at UCLA 33 years ago, began offering the genetic test for familial Mediterranean fever (FMF) as soon as the causative gene was identified 25 years ago. Also during all that time, I have been seeing and treating patients with a suspected diagnosis of FMF both in our Pediatric Genetics Clinic and in UCLA’s uniquely dedicated adult FMF Clinic.
Since Armenians have the highest carrier frequency of any group for that disease (one out of five) and because there are so many Armenian-Americans in Los Angeles, I have gotten to know the local Armenian community of LA and identify with their values. So, there is an emotional passion I have for this project.
What are some of the major goals for this research and how will your findings be used?
Grody: One major goal of the ArmGenia project is technology transfer, at least of the less expensive genetic tests. Once we have demonstrated the clinical utility of these tests in Armenians, we will share the methods with our colleagues in Yerevan so the scientists there can start doing it themselves. While they probably can't do the whole genome, which costs thousands of dollars per patient, they can do two-or-three gene-panel tests.
Akaragian: One of the long-term goals of this global collaboration is knowledge transfer. While the ArmGenia Charitable Trust is associated with several scientific and research institutions that are involved with genetic studies, Armenia does not have geneticists like Dr. Grody, who can perform whole genome or exome sequencing and interpret the data.
Armenia has a sequencing machine; however, due to a lack of expertise and finances, it cannot yet use the technology. Even if they did use the technology, they are not able to interpret the data. The interpretation of data requires an expert in genetics with many years of global experience, and there are only a few scientists/researchers in the world who, like Dr. Grody, have this expertise. Armenians are fortunate to have Dr. Grody lead such an important and innovative project.
We also intend to have a training/mentorship program in Armenia so Dr. Grody can enhance the knowledge of current and future scientists and researchers. Hopefully within five years, Armenia will be able to sustain the project only by consulting with Dr. Grody.
* The Republic of Artsakh, known more commonly as Nagorno-Karabakh, is located within the internationally recognized borders of Azerbaijan — borders that were established by the USSR. Following a referendum for independence from the Azerbaijan SSR held in 1991, and a four-year war, Artsakh has been governed by its indigenous Armenian-majority population as a de facto independent republic for the past 26 years. On September 27, 2020, Azerbaijan attacked the de-facto independent republic, and after 44 days of active warfare, the hostilities ended on November 10th with a ceasefire agreement brokered by Russia. As part of the ceasefire agreement, seven disputed districts in addition to a portion of Artsakh were surrendered to Azerbaijan, regions where some of the samples for this study were collected.