title: Hb Catonsville (glutamic acid inserted between Pro-37(C2)alpha and Thr-38(C3)alpha). Nonallelic gene conversion in the globin system?
abstract: Hb Catonsville is an unstable variant in which glutamic acid is inserted into the alpha-globin chain between Pro-37(C2) and Thr-38(C3). The peptide sequence data are consistent with the DNA sequence of the polymerase chain reaction-amplified fragment of the variant globin gene, which shows the insertion of the triplet codon--GAA--into the mutant alpha-globin gene. In the normal alpha-globin gene cluster the codon for glutamic acid is GAG rather than GAA. Thus, there are two features unique to Hb Catonsville, one the insertion of a single residue into the interior of the alpha-globin chain, and two the presence of the alternate codon for glutamic acid. The experimental evidence suggests that Hb Catonsville may be an example of nonhomologous nonallelic gene conversion, an observation not previously reported in this gene family. The mutation occurs in the critical alpha 1 beta 2 interface of the hemoglobin tetramer and leads to a variant with high oxygen affinity, a reduced cooperativity, and Bohr effect.
authors.affiliation: Division of Host Factors, Centers for Disease Control, Atlanta, Georgia 30333.
authors.forename: W F
authors.initials: WF
authors.lastname: Moo-Penn
authors.forename: D C
authors.initials: DC
authors.lastname: Swan
authors.forename: T K
authors.initials: TK
authors.lastname: Hine
authors.forename: R M
authors.initials: RM
authors.lastname: Baine
authors.forename: D L
authors.initials: DL
authors.lastname: Jue
authors.forename: J M
authors.initials: JM
authors.lastname: Benson
authors.forename: M H
authors.initials: MH
authors.lastname: Johnson
authors.forename: D M
authors.initials: DM
authors.lastname: Virshup
authors.forename: W H
authors.initials: WH
authors.lastname: Zinkham
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D005785:Gene Conversion; D005796:Genes; D014644:Genetic Variation; D005914:Globins / Q000378:metabolism*; D005971:Glutamates; D018698:Glutamic Acid; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011392:Proline; D013912:Threonine; D014357:Trypsin
chemical_list: D005971:Glutamates; D006455:Hemoglobins, Abnormal; D010446:Peptide Fragments; C062183:hemoglobin Catonsville; D013912:Threonine; D018698:Glutamic Acid; D005914:Globins; D011392:Proline; D014357:Trypsin