The number of genes specifying human gamma-globin has been determined directly by hybridization of complementary DNA to total human DNA. The complementary DNA was enriched in sequences specific for gamma-globin genes by transcribing globin mRNA isolated from fetal reticulocytes with viral reverse transcriptase, and collecting the material which does not back-hybridize to adult globin mRNA. When hybridized in cDNA excess to DNA, very similar values are found for gamma-gene number as for beta-gene number, suggesting two or at most three gamma-globin genes per haploid human genome. This indicates that the non-Mendelian ratios of gamma-chain mutants found in heterozygotes are due to transcriptional or post-transcriptional regulation rather than to gene dosage. The number of each major human globin gene has now been determined directly by molecular methods.
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