The effect of alpha-thalassemia on the level of hybrid hemoglobin variants in heterozygotes.
The influence of a relative deficiency in alpha chain production on the amount of Hemoglobins Kenya, P-Nilotic, and Lepore was determined. The level of these hybrid hemoglobins in heterozygotes was correlated to various states of alpha chain deficiency by: 1) quantitation of the variants in blood samples and comparing these data with the number of alpha globin genes determined by gene mapping, 2) in vitro recombination experiments involving isolated non-alpha chains and normal alpha chains, and 3) in vitro heat stability analyses of the isolated hemoglobins. Hb Kenya, composed of normal alpha and gamma-beta hybrid chains, is heat labile, has a decreased ability to combine with alpha chains, and its level in heterozygotes is greatly decreased when a concomitant alpha-chain deficiency (alpha-thalassemia) is present. Such a posttranslational control mechanism was not observed for Hb Lepore, with normal alpha chains and delta-beta hybrid chains, and Hb P-Nilotic, with normal alpha chains and beta-delta hybrid chains. The latter two variants are heat stable, and their hybrid chains combine equally well as normal beta chains with normal alpha chains. Hb P-Nilotic is more heat stable than Hb A and its in vitro formation is increased over that of Hb S, and perhaps even Hb A, in conditions of severe alpha chain deficiency.
D005319:Fetal Hemoglobin / Q000235:genetics / Q000378:metabolism; D005914:Globins / Q000172:deficiency / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D006824:Hybridization, Genetic; D011487:Protein Conformation; D013789:Thalassemia / Q000097:blood* / Q000235:genetics
D006455:Hemoglobins, Abnormal; C049659:hemoglobin P-Nilotic; C040843:hemoglobin Kenya; D005914:Globins; D005319:Fetal Hemoglobin; C037659:hemoglobin Lepore