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Fifty-Eight Years of Hemoglobin Analysis

Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand, and, Christchurch School of Medicine, University of Otago, E-mail steve.brennan@otago.ac.nz

The first 20% of the full text of this article appears below.

Hemoglobinopathies are the archetypal molecular disease, and from 1949, when Linus Pauling et al. first demonstrated that hemoglobin (Hb) S could be separated from Hb A by paper electrophoresis (1), the detection and identification of Hb variants has provided a testing ground for new methods of protein analysis. The actual molecular basis of sickle cell anemia was not finally elucidated until 1959, when Vernon Ingram perfected the techniques of tryptic peptide fingerprinting (2). These modest beginnings led to the evolution of more sensitive analytical techniques, and the number of structurally characterized Hbs has now expanded to more than 1000 known variants.

During the 1960s and 1970s, 2-dimensional peptide mapping on paper and ion exchange mapping on Dowex resins led to the identification of many new variants until these techniques were eventually superseded by reversed-phase HPLC in the 1980s. Along with the introduction of reversed-phase chromatography, the need for more readily automated procedures for the quantification of HbA₂ and HbF for thalassemia assessment and HbA1c in relation to diabetic control led to the introduction of cation exchange HPLC systems as a means of separating Hb species. Because thalassemia is the most common genetic disease world wide, and because of the prevalence of diabetes in western cultures, many ion exchange separations are performed annually, leading to the incidental detection of large numbers of "interfering" Hb variants. In the 1990s, refinements of soft-ionization techniques, such as fast atom bombardment, electrospray, and matrix-assisted laser desorption, heralded the introduction of protein mass spectrometry, and those working on Hb analysis were among the first to exploit the power of this new technology in a diagnostic setting.

In this issue of Clinical Chemistry, Kleinret and colleagues (3) provide . . . [Full Text of this Article]