G gamma and A gamma globin genes are identical from -471 of the promoter midway through gamma IVSII in a Benin beta s haplotype associated with elevated fetal hemoglobin.
In seven kindreds in which sickle cell (SS) patients had elevated (greater than 12%) fetal hemoglobin (Hb F), Milner and colleagues reported that a determinant for elevated Hb F and elevated F cells was linked to the beta s gene. Independently, the Senegal (SEN) beta s haplotype has been found in association with elevated Hb F in SS and beta-thalassemia patients. We have used the kindreds of Milner and colleagues to characterize further the association of haplotype and gamma gene DNA sequence variation with Hb F expression. For the largest kindred, Wi, all four SS had high (greater than 14%) Hb F and both SEN and Benin (BEN) haplotypes. Two AS cases carrying SEN had low Hb F and low F cells, while three AS and one CS carrying BEN had elevated Hb F and elevated F cells; only one AS carrying BEN had low Hb F and low F cells. In order to look for genetic alterations that could account for the elevated Hb F of kindred Wi, we sequenced both the G gamma and A gamma genes of the Wi BEN haplotype. The data showed largely identical G gamma and A gamma genes which may have been generated by two gene conversions: the A gamma promoter was like that of G gamma 3' to -471, while the G gamma IVSII was like that of A gamma in its 5' half. In addition, three new mutations were found in gamma IVSII.(ABSTRACT TRUNCATED AT 250 WORDS)
Mishima
N
N
Albert Einstein College of Medicine, Bronx, NY.
Brinson
E C
EC
Milner
P F
PF
Gilman
J G
JG
D000755:Anemia, Sickle Cell / Q000235:genetics; D001483:Base Sequence; D005319:Fetal Hemoglobin / Q000032:analysis*; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid
D005914:Globins; D005319:Fetal Hemoglobin