Rose G. Schneider

Measuring Relative Electrophoretic Mobilities of Mutant Hemoglos and Globin Chains

A system of calculating relative mobilities of mutant hemoglobins and globin chains in four methods of zone electrophoresis is described. In electrophoresis on cellulose acetate, TEB buffer, pH 8.5, mobilities are calculated as ratios of the mobility of simultaneously analyzed Hb C. In electrophoresis on citrate agar, pH 6.0, anodic mobilities are also related to Hb C, cathodic ones to Hb F. In globin electrophoresis in urea 2-mercaptoethanol buffers, pH 6.0 and 8.9, mobilities of the mutant globin chains are calculated in relation to the mobilities of normal alpha and beta chains. These calculations provide objective comparisons of mobilities of hemoglobins, including those analyzed at different times. The combined data permit recognition of many mutant hemoglobins.

Hemoglobin sabine beta 91 (f 7) leu to pro. An unstable variant causing severe anemia with inclusion bodies.

Abstract Hemoglobin Sabine (α2β2 91 leu → pro) comprises 8 per cent of the hemoglobin of a 16-year-old Scotch-English-German girl who has suffered from hemolytic anemia since infancy. The spleen wa...

Haemoglobin titusville: α94 Asp → Asn: A new haemoglobin with a lowered affinity for oxygen

Abstract A new haemoglobin variant with a decreased oxygen affinity is described, in which the substitution, α94 (G1) Asp → Asn, affects the α1β2 contact α1G1-β2G4. The relevance of this variant to our understanding of the importance of the hydrogen bond between α1G1 and β2G4 in Perutzs model of oxyhaemoglobin A is discussed.

Genetic Haemoglobin Abnormalities in about 9000 Black and 7000 White Newborns; Haemoglobin F Dickinson (Aγ97 HisÅg), a New Variant

Summary. Electrophoretically detectable haemoglobin abnormalities are readily identified in umbilical cord blood haemolysates by cellulose acetate electrophoresis, followed by citrate agar electrophoresis of those samples exhibiting an abnormality, and, if necessary, by globin electrophoresis. In samples from 9224 Black newborns, the prevalence of all such abnormalities was about 13%, with 12 cases of sickle‐cell anaemia, seven of Hb‐SC disease and five of Hb‐S β thalassaemia. Clinical and haematologic manifestations of these conditions usually appeared in the first few years of life. The prevalence of sickle‐cell trait was about 7%, Hb‐C trait 2%, and Hb Barts 5%. Several new or rare haemoglobins, both adult and foetal, were found in individual families.

Two new hemoglobins: Hemoglobin Alabama [β39(C5)Gln → Lys] and hemoglobin Montgomery [α48(CD6)Leu → Arg]

Abstract The amino acid substitutions in two new hemoglobins found by electrophoretic screening during a survey in Alabama have been determined by column chromatography and amino acid analyses of their tryptic peptides. They are hemoglobin Alabama [β 39(C 5)Gln → Lys] and hemoglobin Montgomery [α 48(CD 6)Leu → Arg]. No harmful symptoms have been attributed to the presence of either hemoglobin.

A variant present in unusually low concentration

Hb Ft. Worth, α27Glu → Gly(B8), constitutes about 5% of the hemoglobin of two members of a Negro family, both of whom exhibit slight hypochromia and microcytosis.

Sickle cell anemia in the first 2 years of life

Summary Studies are presented on 54 Negro children with sickle cell anemia, of whom 26 were examined and the diagnosis found before the age of 2 years. In 2 siblings, one studied from birth and the other from the age of 6 weeks, there was no strict correlation between the rise in S hemoglobin, the reciprocal fall in F hemoglobin, and the development of symptoms. Clinical manifestations did not appear in any of the 54 children before 3 months of age. Symptoms were noted, however, either by personal observation or by history in about one half of the patients before the age of 1 year and in three fourths of the patients before 2 years of age. Particularly noteworthy findings were the osteopathy involving, primarily, the metacarpals and proximal phalanges, and the splenomegaly, which in 4 instances was associated with thrombocytopenia.

Structure in Relation to Behavior of Mutant Hemoglobins in Citrate Agar Electropiioresjs

The comparative mobilities, in citrate agar electrophoresis, of 91 mutant hemoglobins are presented in relation to their molecular structure and in some cases, to their mobilities in other types of electrophoresis. More than a third of the alpha chain mutants (11 of the 27 examined) and half of the beta chain mutants (29 of 55) differ to some extent from Hb A. The helical location of the substituted residue is an important determinant of hemoglobin mobility, which is also affected by a complex interplay of other factors. When the data are combined with those of several other types of electrophoresis, they often provide presumptive (or in some cases highly specific) identifications of mutant hemoglobins and hemoglobinopathies.

Sickling, a quantitatively delayed genetic character.

Summary Positive sickling was found in 7 or 8.3% of blood samples from 84 newborn Negro babies, with 3 to 15% of erythrocytes capable of sickling. In free electrophoresis of the hemoglobin of 4 of these 7, the S hemoglobin content ranged from “not demonstrable” to 21%. Blood samples from one baby with sicklemia were studied at birth, 2 weeks, 6 weeks and 7 months respectively, with a progressive increase of sickling erythrocytes of from 13% at birth to 97% at 7 months, and a corresponding increase in S hemoglobin of from about 14 to 50%. Three of the other babies with sicklemia were reexamined at 41/2 to 7 months, at which time almost 100% of the erythrocytes sickled and S hemoglobin values were of the adult order of 40 to 50%. The presence of hemoglobin C trait was detected in the blood of one new-born baby of the 84, with a hemoglobin C content of only 8%. The rarity of sickle cell anemia and the paucity of sickling erythrocytes in young infants are explained by a quantitative delay in the production of S hemoglobin which, like normal adult hemoglobin (and probably hemoglobin C), does not reach adult levels until the age of about 41/2 months.

Hemoglobin Fannin-Lubbock [alpha 2 beta 2 119(GH2) Gly replaced by Asp]. A slightly unstable mutant.

Abstract Hb Fannin-Lubbock [α2β2119(Gh2)Gly Asp] was found in four members of a Mexican-American family. It has the substitution Gly a Asp at Residue 119 of the beta chain, which is an α1β1 contact. The hemoglobin is unstable to heat and isopropanol, but has normal oxygen affinity. It is not associated with marked clinical and hematologic abnormalities, but one of the carriers exhibits a slight anemia.