Keolu Fox, Ian B. Stanaway, Jill Johnsen and Deborah A. Nickerson
AAPA 2018, Meeting Program Abstracts
April 11-14, 2018
Characterizing variation in the ABO gene is important in transfusion and transplantation medicine because variants in ABO have significant consequences with regard to recipient compatibility. While many believe that the genetics of the ABO locus is well understood, little is known about the impact of novel, rare variation in the ABO gene. Here, we analyze next-generation sequence derived coding variation in ~2,500 individuals from 28 populations, including two ancient hominins (Neanderthal and Denisovan). We hypothesize that imputed ABO types from the 1,000 Genomes Project will recapitulate previous estimates based on serologically derived ABO blood types (Cavalli-Sforza et al., 1994) and allow us to impute ABO haplotype structure in ancient hominins. Through our analysis, we validated previous estimates of ABO blood type based on serology. We identified common variants known to influence ABO function, including those known to the common A and B haplotype as well as a common deletion that leads to the O genotype. We also identified rare population specific coding variants within ABO including single nucleotide/missense variants and insertion/deletions. We then used those haplotypes to impute ABO blood type for both ancient hominins.
These analyses are important for future studies of human blood group genes to (1) improve the specificity of blood typing at both the clinical and research level by identifying rare functional alleles that might result in atypical serological patterns, (2) illuminate ABO gene architecture on a global scale, and (3) assess the potential for introgression of ancient ABO haplotypes found in contemporary human populations.