A 4-BASE-PAIR DELETION 5' TO THE (A)GAMMA(T) GENE IS ASSOCIATED NOT ONLY WITH DECREASED EXPRESSION OF THE (A)GAMMA(T)-GLOBIN GENE, BUT ALSO OF THE (G)GAMMA-GLOBIN GENE IN CIS

A four base pair deletion 5' to (A) gamma(T)-globin gene at positions -222 to -225 has been reported to reduce the expression of this gene. To evaluate the prevalence and effect of this deletion, PCR-based methods were employed. The deletion had a gene frequency of 0.06 in a sample of African-American individuals with sickle cell trait, 0.18 in adult African-Americans with normal Hb AA, and 0.36 in caucasians. Seventy cord blood samples from African-American newborns with Hb AA were evaluated by both HPLC and PCR. The frequency of the (A) gamma(T) allele was 0.13. The (A) gamma(T)-globin chain was always present in a lower proportion than the (A) gamma(I) allele (70% of (A) gamma(I)), but the percentage of (A) gamma-globin was the same whether or not (A) gamma(T) was present. The total percentage of Hb F, however, was significantly lower in the group with the (A) gamma(T) allele (77.1% vs. 87.4%, P < 0.01). These results indicate that the four base pair deletion is not only associated with reduced expression of the (A) gamma(T) allele, but also of the (G) gamma allele in cis, further suggesting a possible role of this region in the modulation of the expression of the linked gamma-globin genes. (C) 1994 Wiley-Liss, Inc.