Dysfunctional α-globin genes in hemoglobin H disease in blacks: Variation in restriction fragment size permits the detection of the -α/-αT genotype

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Abstract
Hemoglobin H (HbH) disease is most often due to deletion of three of the four α‐globin genes (genotype ‐ ‐ ‐ ‐/‐α). In black subjects although the ‐α/chromosome is common, the ‐ ‐/haplotype is very rare and few examples of HbH disease have been detected. We have studied three black siblings with HbH by restriction endonuclease mapping of the α‐like gene complex (5′‐ζ‐Ψζ‐Ψα2‐Ψα1‐α2‐α1‐3′) using ζ‐ and α‐ specific probes. The presence of size differences in the previously described hypervariable region between the ζ and ζΨ genes results in a restriction fragment length polymorphism which permitted the detection of single α genes on both number 16 chromosomes in these subjects. Quantitative DNA hybridization by a slot‐blot technique confirmed that their genomes contained two α‐globin genes. The results establish that in these black subjects HbH disease is associated with dysfunctional α‐globin genes (genotype: ‐α/‐αT).