Characterization of α- and β-thalassemia alleles in the SGP cohort. (A) The extended α-globin locus on chromosome 16. The α-globin genes HBA1 and HBA2 are indicated on top. X1 and X2, Y1 and Y2, and Z1 and Z2 represent duplicated regions with high sequence similarity where unequal crossing over generates gene deletions. The α-thalassemia deletion −α^3.7 was identified by reduced density of sequencing reads within the indicated assembled contig. The number and percentage of −α^3.7 homozygotes and heterozygotes identified in the SGP cohort are shown at right. (B) Agarose gel fractionation of multiplex PCR products show wild-type α globin and −α^3.7 alleles.³¹ We analyzed the genotypes of 75 randomly chosen samples by PCR (indicated at the bottom of the panel) to validate WGS calls for heterozygous or homozygous −α^3.7. (C) Discrepancy between clinical assignments and genetic determinations of HbSS and HbSβ⁰ thalassemia genotypes in the SGP cohort. The first 2 pie charts show the WGS-derived genotypes of individuals who were previously assigned clinical diagnoses of HbSS or HbSβ⁰-thalassemia. The third pie chart shows the α-thalassemia status of 18 individuals in whom HbSβ⁰-thalassemia was incorrectly diagnosed.