A large part of human genetic disease apparently arises from deamination of cytosines in methylated CpG dinucleotides. Their mutation rate is known to be high when C is present as 5-methylcytosine, but is believed to be normal when it is unmethylated. The beta-globin gene contains five, the gamma-globin gene two, and each of the alpha-globin genes contain 35 CpGs. The CpGs in the beta- and gamma-globin genes are methylated, while those in the alpha-globin genes are undermethylated. One would therefore have expected the CpGs to be a frequent source of mutations in the beta- and gamma-globin genes, but not in the alpha-globin genes. In fact, the evidence points to CpGs being a frequent source of mutations in both the alpha- and beta-globin genes. This suggests either that the mutation rates of both methylated and unmethylated CpGs are abnormally high, which conflicts with published evidence, or that there is a finite chance of some CpGs in the alpha-globin genes of certain individuals being methylated and therefore subject to mutation.