Variant Bio Launches New Partnership with the University of Antananarivo, Madagascar
Madagascar, an island country some 300 miles east of southern Africa, which typically conjures images of lemurs and baobab trees, has only been populated by humans for about 2000 years.¹,² As biological anthropologist Dr. Laurie Godfrey recounts, since Madagascar was likely an important stopping point along a trade route that ran between southeast Asia and east Africa, the cultural practices of today’s Malagasy people reflect their mixed Asiatic and African roots.³ It is precisely because these two ancestral populations of continental African and Southeast Asian descent are thought to have independently settled the island and subsequently mixed together that Malagasy people possess a unique genetic background.⁴ Moreover, different parts of Madagascar are thought to be inhabited by populations which are genetically diverse, showing a striking regional variability for a fairly small island — for example, among peoples who live in the highlands versus those residing on the coast.⁵,⁶ Malagasy people as a whole and specifically these sub-populations may have developed genetic differences that resulted in globally rare but locally common genetic variation that could have significant implications for individual health.
Yet, like so many populations of non-European ancestry around the world, the people of Madagascar remain significantly underrepresented in both genetic studies and accompanying health research. As far as we at Variant Bio are aware, there is not a single Malagasy whole-genome dataset in any public database. To help better understand the genetic diversity on the island, Variant Bio is partnering with a team of researchers at the University of Antananarivo’s Department of Anthropobiology and Sustainable Development, in the capital city of Madagascar, to conduct a pilot project with communities living in different locations throughout the country.
Variant will build on previous work conducted in Madagascar that identified different clusters of genetic diversity across the country. Based on what Variant and researchers at the University of Antananarivo know already from these studies, we believe that the coastal populations of Madagascar should be skewed towards a larger genetic contribution from continental African ancestry and the highlands populations will have a higher proportion of Asian ancestry.¹,⁵ This likely reflects regional differences in settlement by ancestral African and Asian populations,¹,⁵,⁶ though it is believed that a higher burden of malaria in coastal regions compared to the highlands may have also contributed to the varying ancestry patterns across the island.² Alleles of African origin have been favored in a region spanning ~25% of chromosome 1 in Malagasy genomes, representing one of the strongest signals of recent selection reported for modern humans.²,⁶,⁷ This region includes the Duffy blood group gene.² The Duffy null allele provides resistance to malaria (Plasmodium vivax), pointing to malaria as the most likely driver of selection. Furthermore, this selection event may have affected numerous genes associated with asthma, Crohn’s disease, type 1 diabetes, and other immunological disorders.²
Thus, as a part of this project, our partners will collect relevant health information from study participants to begin to understand if those known versions of genes indeed contribute to disease epidemiology in Madagascar. We will additionally collect genetic samples for whole-genome sequencing and focus our analysis on the regions of positive selection in highland and coastal populations.
Our research partners at the University of Antananarivo include three biological anthropologists — Dr. Rindra Rakotoarivony, who has a PhD in the Anthropology of Human Genetics, Pr. Germain Jules Spiral, Head of the Laboratory of Physical Anthropology, and Dr. Soanorolalao Ravelonjanahary, a senior member of the Laboratory of Physical Anthropology— as well as Dr. Jean Freddy Ranaivoarisoa, Former Head of the Department and now Head of both the Genetics Laboratory and the Primatology Laboratory, and Dr. José Mahenina Randria, a state-qualified physician serving in the Faculty of Medicine.
Since co-designing the project and signing a research agreement with the University of Antananarivo, we have obtained authorization to carry out the study from the relevant national ethics committee of Madagascar. Between December 2020 and February 2021, our partners from the University of Antananarivo also spent a total of three weeks visiting potential study locations on the western coast and in the highlands as part of a formal community consultation process that Variant undertakes for every one of our projects around the world (for more on our general approach to ethics and community engagement, see here). During these field visits, the University of Antananarivo team met with community leaders, key stakeholders, and ordinary citizens in each potential study location to explain the purpose of the project, assess local interest and study feasibility, and discuss any ideas, questions, and/or concerns that people might have about it.
Additionally, our partners gathered input from community members about the most meaningful initiatives that Variant might support as part of our benefit sharing program (for more on our overarching mission and official commitment to giving back to the communities who share their genetic and health information with us, see here). For example, some community members emphasized a desire to improve medical facilities, while others highlighted the need for a new public fountain with clean drinking water or better school infrastructure.
Now that the project design, community consultation, and ethics approval process are complete, our partners at the University of Antananarivo are ready to begin the study in select locations throughout Madagascar. They will, of course, be taking every precaution necessary to keep themselves and participating communities safe from COVID-19. Our aim is to complete the sample and health information collection before the wet season makes the roads from Antananarivo to the small, inland and coastal villages impassable later this year.
- Pierron, Denis., et al. “Genomic landscape of human diversity across Madagascar.” PNAS (2017): E6498–E6506.
- Pierron, Denis., et al. “Strong selection during the last millennium for African ancestry in the admixed population of Madagascar.” Nature Communications, (2018), 9:932.
- https://www.pbs.org/edens/madagascar/eden.htm.
- Pierron, Denis., et al. “Genome-wide evidence of Austronesian–Bantu admixture and cultural reversion in a hunter-gatherer group of Madagascar.” PNAS (2014): 936–941.
- Rakotoarivony, Rindra. et al. “Genomic investigation of the ancestry proportion of six Malagasy ethnic groups.” Human Population Genetics: The Origin of the Population of Madagascar (2019), 29–32.
- Heiske, Margit, Omar Alva, Veronica Pereda-Loth, Matthew Van Schalkwyk, Chantal Radimilahy, Thierry Letellier, Jean-Aimé Rakotarisoa, Denis Pierron. “Genetic evidence and historical theories of the Asian and African origins of the present Malagasy population,” Human Molecular Genetics, Volume 30, Issue R1, 1 March 2021, Pages R72–R78.
- Hodgson, J.A., Pickrell, J.K., Pearson, L.N., Quillen, E.E., Prista, A., Rocha, J., Soodyall, H., Shriver, M.D. and Perry, G.H. (2014) Natural selection for the Duffy-null allele in the recently admixed people of Madagascar. Proc. R. Soc. B Biol. Sci., 281, 20140930.
