229W Poster - Population Genetics
Wednesday June 08, 9:15 PM - 10:00 PM

Authors:
Paige E. Haffener ¹; Arwa Z. Al-Riyami ²; Shoaib Al-Zadjali ³; George B. J. Busby ⁴; Mohammed Al-Rawahi ⁵; Saif Al Hosni ²; Ali Al Marhoobi ⁵; Ammar Al Sheriyani ⁶; Ellen M. Leffler ¹

Affiliations:
1) Department of Human Genetics, The University of Utah, Salt Lake City, UT, USA; 2) Department of Hematology, Sultan Qaboos University Hospital, Muscat, Oman ; 3) Sultan Qaboos Comprehensive Cancer Center, Muscat, Oman ; 4) Allelica, London, UK ; 5) Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman ; 6) Royal Oman Police Hospital, Muscat, Oman

Keywords:
Natural selection

Oman is a country in the southeast corner of the Arabian Peninsula (AP) that historically struggled with malaria endemicity caused by both Plasmodium falciparum and P. vivax. AP populations in the southern region of the peninsula show genetic admixture with African populations, introduced partly through the Arab slave trade, providing a source for malaria-protective variants that may have been selected for in the Omanis. Indeed, the Duffy null allele at the DARC locus, which confers protection from P. vivax malaria, shows intermediate frequencies and excess African ancestry in several AP and other admixed populations consistent with post-admixture selection. We hypothesize that variants protective against P. falciparum malaria, including several other blood group variants, may also have been introduced by admixture and undergone subsequent positive selection. To test this, we generated whole genome sequence data with paired serological phenotypes for 10 blood groups, including three that have been associated with malaria, from 100 native, healthy Omani blood donors. Concordance between serological and genetically inferred phenotypes was high for all blood groups, with most mismatches explained by rare or novel coding and structural variants. Notably, we identify a distinct Duffy-null allele in Oman that is present across other AP populations but absent elsewhere. We also report the presence of the Dantu variant in the MNS blood group system, which was recently found to be protective against P. falciparum malaria and previously reported only in East African populations. Global admixture inference further supports significant admixture with East African populations, consistent with the history of the Omani empire. Local ancestry inference using RFMix2 indicates an excess of African ancestry in Omanis at the DARC locus, suggestive of positive selection. Ongoing work includes additional tests for selection at DARC and other malaria-protective loci.