Fig. 2

RMCs originate in patients with diverse sickle cell haplotypes. a Heatmap depicting the mutation status of each HBB allele in RMC patients. Patients carrying the canonical Glu6Val (rs334) sickle cell mutation are as indicated. b Principal component analysis of haplotypes carrying the sickle cell mutation or the wild-type HBB allele in RMC patients. Sickle cell trait and reference haplotypes corresponding to different populations from the 1000 Genome database are also depicted for comparison. The percentage of variation explained by each principal component (PC) is as indicated. Arrows in magenta highlight the sickle cell mutant haplotypes of RMC patients which are broadly separated into three different population groups. Population codes represented in the figure are as follows: ACB, African Caribbeans in Barbados; ASW, Americans of African ancestry in southwest USA; CLM, Colombians from Medellin, Colombia; ESN, Esan in Nigeria; GWD, Gambian in Western Divisions in the Gambia; LWK, Luhya in Webuye, Kenya; MSL, Mende in Sierra Leone; PUR, Puerto Ricans from Puerto Rico; and YRI, Yoruba in Ibadan, Nigeria. Note that numerous sickle cell mutant haplotypes were nearly identical, causing them to appear as overlapping points on the plot. c Fine-mapping analysis was performed to identify the variants that are significantly enriched in the sickle cell mutant haplotypes but depleted in the reference haplotypes for variants sorted by genomic coordinates. The dotted line represents a p-value of 10⁻⁶