title: Hemoglobin Birmingham and hemoglobin Galicia: two unstable beta chain variants characterized by small deletions and insertions.
abstract: Two unstable hemoglobins (Hbs) causing rather severe hemolytic anemia have been characterized. The beta chain of Hb Birmingham, found in an adult black man, is characterized by the loss of -Leu-Ala-His-Lys- at positions 141, 142, 143, and 144 and their replacement by one Gln residue. These changes are the result of a deletion of nine nucleotides, namely two base pairs (bp) of codon 141, all of codons 142 and 143, and one bp of codon 144; the remaining CAG triplet (C from codon 141 and AG from codon 144) codes for the inserted glutamine. In the beta chain of Hb Galicia from a Spanish patient, His and Val at positions 97 and 98 are replaced by one Leu residue. This is due to an ACG deletion in codons 97 and 98, which causes the removal of one His and one Val residue, while the remaining CTG triplet (C from codon 97 and TG from codon 98) codes for the inserted leucine residue. Two mechanisms, namely slipped mispairing in the presence of short repeats, and misreading by DNA polymerase due to a local distortion of the DNA helix, are considered in explaining the origin of the small deletions.
authors.affiliation: Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: J B
authors.initials: JB
authors.lastname: Wilson
authors.forename: B B
authors.initials: BB
authors.lastname: Webber
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.forename: A
authors.initials: A
authors.lastname: Kutlar
authors.forename: F
authors.initials: F
authors.lastname: Kutlar
authors.forename: J F
authors.initials: JF
authors.lastname: Codrington
authors.forename: J T
authors.initials: JT
authors.lastname: Prchal
authors.forename: K M
authors.initials: KM
authors.lastname: Hall
authors.forename: J M
authors.initials: JM
authors.lastname: de Pablos
authors.forename: I
authors.initials: I
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002848:Chromatography, DEAE-Cellulose; D002872:Chromosome Deletion; D004251:DNA Transposable Elements; D005260:Female; D005784:Gene Amplification; D014644:Genetic Variation; D006455:Hemoglobins, Abnormal / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D010449:Peptide Mapping; D014357:Trypsin
chemical_list: D004251:DNA Transposable Elements; D006455:Hemoglobins, Abnormal; D046911:Macromolecular Substances; D010446:Peptide Fragments; C063971:hemoglobin Birmingham; C063972:hemoglobin Galicia; D014357:Trypsin