title: Hemoglobin Montreal: a new variant with an extended beta chain due to a deletion of Asp, Gly, Leu at positions 73, 74, and 75, and an insertion of Ala, Arg, Cys, Gln at the same location.
abstract: The unstable hemoglobin Montreal with a deletion of three amino acid residues (Asp, Gly, Leu) at positions 73, 74, and 75 of the beta chain and an insertion of four residues (Ala, Arg, Cys, Gln) at the same location was observed in a 7-year-old Canadian boy suffering from a moderate hemolytic anemia. The introduction of an extra amino acid residue and of other changes in the crevice where the heme group is located is the likely cause of the instability of this hemoglobin variant. The above listed changes were detected through analyses of tryptic peptides of the beta-Montreal chain, sequencing of amplified DNA, and hybridization of amplified DNA with appropriate, 32P-labeled, oligonucleotide probes. It is suggested that a mispairing involving the AGTG sequences at codons 66 and 67 and at codons 72 and 73 of the normal beta gene caused a repetition of a 16-bp segment, while a deletion of 10 nucleotides due to recombination or slippage followed by a second short deletion during DNA repair resulted in the modified sequence of the beta-Montreal gene.
authors.affiliation: Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: D
authors.initials: D
authors.lastname: Plaseska
authors.forename: A J
authors.initials: AJ
authors.lastname: Dimovski
authors.forename: J B
authors.initials: JB
authors.lastname: Wilson
authors.forename: B B
authors.initials: BB
authors.lastname: Webber
authors.forename: H A
authors.initials: HA
authors.lastname: Hume
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002851:Chromatography, High Pressure Liquid; D002872:Chromosome Deletion; D004251:DNA Transposable Elements; D005260:Female; D005784:Gene Amplification; D014644:Genetic Variation; D006441:Hemoglobin A / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010446:Peptide Fragments / Q000302:isolation & purification
chemical_list: D004251:DNA Transposable Elements; D006455:Hemoglobins, Abnormal; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; C066708:hemoglobin Montreal; D006441:Hemoglobin A