A Silent, Neutral Substitution Detected by Reverse-Phase High-Performance Liquid Chromatography: Hemoglobin Beirut

• Published in: Science (American Association for the Advancement of Science) Vol. 221; no. 4613; pp. 860 - 862
• Main Authors: Strahler, John R., Rosenbloom, Barnett B., Hanash, Samir M.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 26-08-1983; American Association for the Advancement of Science
• Subjects: Adult; Amino acids; Anemias. Hemoglobinopathies; Artificial satellites; Biochemistry; Biological and medical sciences; Chromatography, High Pressure Liquid; Diseases of red blood cells; Genetic variation; Hematologic and hematopoietic diseases; hemoglobin Beirut; Hemoglobins; Hemoglobins, Abnormal - genetics; Hemoglobins, Abnormal - isolation & purification; high-performance liquid chromatography; Human genetics; Humans; Isoelectric Point; Liquid chromatography; Macromolecular Substances; Male; man; Medical sciences; Neutral amino acids; Plasmids; Solvents; Hemoglobinopathy; Chromatography
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.6879181

A substitution of alanine for valine at position 126 in the β -chain of hemoglobin was discovered in a hematologically normal adult male of Lebanese extraction. The variant β-globin was initially observed and subsequently purified by reverse-phase high-performance liquid chromatography (HPLC). Reverse-phase HPLC was also used to isolate the variant tryptic peptide of β-T13 that has alanine replacing valine at residue 126. The discovery of hemoglobin Beirut illustrates the usefulness of reverse-phase HPLC for the detection of neutral amino acid substitutions in proteins. The ability to detect neutral substitutions in undigested proteins is pertinent to the monitoring of genetic variation in human populations.