A fetal hemoglobin variant of unusual genetic interest.

T HE HUMAN HEMOGLOBINS consist of two pairs of peptide chains.1’2 Adult hemoglobin ( Hb-A ) has two chains designated a and two chains designated iB; it is thus represented as 2A $2A#{149}Fetal hemoglobin (Hb-F ) has two a chains, which are similar if not identical in structure to those of Hb-A, but a pair of chemically distinct chains, the y chains replacing the $ chains.3’4 Hb-F is thus represented as a2Ay2F’. Abnormal hemoglobins have been described with structural alterations in either the a or the chains.5 For example, hemoglobins S and C have been shown to have an amino acid substitution in the $ chain,5 while hemoglobins Hopkins 2, I and Gr’l,lladeJpI,ja have a substitution in the a chain.#{176}8 The last stage of assembly of the hemoglobin molecule is thought to be the combination of symmetric dimers, i.e., dimers made up of two identical peptide chains.8 Random combination of these dimers has been shown in individuals doubly heterozygous for a and $ abnormal genes.8 The change from fetal to adult hemoglobin synthesis in early infancy may be considered to he due to a switch from y to $ chain production. !f the synthesis of the a peptide chains of Hh-A and of Hb-F is under the control of the same gene, an infant who had inherited an abnormal aX gene from one parent would be expected to show beside Hh-F an abnormal fetal ( a2Xy2F ) hemoglobin resulting from the combination of abnormal a dimers with Y2 ’ dimers. An abnormal fetal hemoglobin, characterized by an altered electrophoretic mobility, has been described recently in newborns by Minnich and her associates,9 and by Weatherall and Bover.1#{176}One of the parents of each of these infants showed Hb-D trait. The Hh-D5, of Minnich is identical to F!h-G ,115. by fingerprinting analysis (Baglioni, unpublished) and thus altered in the a chain. Recombination experiments showed that an abnormal a chain was present in the Hb-D described by Weatherall and Boyer1#{176}and in the abnormal fetal hemoglobin found in the infants reported by them. In a survey of the hemoglohins in the umbilical cord blood of Negroes in Baltimore, a further case has been found of an abnormal fetal hemoglobin occurring in an infant who had inherited an abnormal a chain gene. A sufficiently large sample of cord blood was obtained to carry out a detailed chemical study, which forms the subject matter of the present paper.