title: A four 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.
abstract: 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.
authors.affiliation: Molecular Hematology Laboratory, VA Medical Center, Jackson, MS 39216.
authors.forename: M B
authors.initials: MB
authors.lastname: Coleman
authors.forename: J G
authors.initials: JG
authors.lastname: Adams
authors.forename: M H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: W P
authors.initials: WP
authors.lastname: Winter
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005319:Fetal Hemoglobin / Q000235:genetics*; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D017931:DNA Primers; D005914:Globins; D005319:Fetal Hemoglobin