Structural analysis of a new variant hemoglobin revealed tryptic peptides with the amino acid composition of normal delta-globin, except for two internal peptides, which had the compositions of normal beta-globin. The most likely explanation for these findings is that a double, nonhomologous crossover between the delta-and beta-globin genes had occurred.

Communicated byJames V. Neel, October 8, 1980 ABSTRACT Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination ofhis hemolysate revealed 87.5% Hb F, 3.4% HbA2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion ofleucine at f75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The a/non-a biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and (3-thalassemia, Hb Vicksburg should have comprised the major portion ofthe hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of iv mRNA; in individuals with Hb St. Antoine ((374 and (75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of

Hb Mississippi was discovered in a 6-year-old Chinese girl with chronic anemia and thalassemia intermedia. Family studies revealed that she had inherited the Hb Mississippi from her father as well as inheriting a gene for beta+-thalassemia from her mother. Electrophoretic analyses of the hemolysate of the father of the father and the proband on polyacrylamide gels at pH 8.6 showed that the abnormal hemoglobin had three distinct mobilities. A similar pattern was also observed by isoelectricfocusing. In addition, multiple abnormal peaks were observed by high performance liquid chromatographic hemoglobin separations as well as high performance liquid chromatographic globin chain separation. Structural analysis of the abnormal hemoglobin demonstrated a single abnormality; the substitution of serine to cysteine at position 44 (CD3) of the beta-globin chain. Since CD3 is on the surface of the beta-globin chain, it was thought that polymerization of the abnormal hemoglobin by disulfide linkages might have been responsible for the anomalous behavior on electrophoresis and high performance liquid chromatography. Gel filtration chromatography on G-200 Sephadex confirmed this supposition and demonstrated that the abnormal globin chain polymerized with itself as well as with other globin chains.

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