H. F. Harris

A Search for Anomalies in the ζ,α,β, and γ Globin Gene Arrangements in Normal Black, Italian, Turkish, and Spanish Newborns

Globin gene mapping analyses of DNA from numerous Black babies, and from newborns from Sardinia, Sicily, Turkey, and Spain have identified the followingA high incidence of α-thalassemia-2 heterozygotes among Black babies with less than 1% Hb Barts at birth and a high incidence of α-thalassemia-2 among Sardinians, but not among Sicilian, Turkish, and Spanish babies. A relatively high incidence of ζ-thalassemia was present among Black babies only, while triplicated ζ was seen in four of the five populations. Two Black babies were each found to have a different θl deletion; two Sardinian babies had a newly discovered β 2.5 kb deletion between ζ and ψζ; four babies had the rare Bgl II polymorphism between ψζ and ψα; and one Black baby lacked the Eco RI site 3’ to ζ Quantitation of the ζ chain by reversed phase high performance liquid chromatography showed that two-thirds of the babies with four α genes (αα/αα) had levels between 0.1 and 1.0%, while nearly 90% of the babies with -α/αα had similar levels (aver...

The Synthesis of Fetal Hemoglobin Types in red Blood Cells and in BFU-E Derived Colonies from Peripheral Blood of Patients with Sickle Cell Anemia, β+- and δβ-Thalassemia, Various forms of Hereditary Persistence of Fetal Hemoglobin, Normal Adults and Newborn

The biosynthesis of two types of human fetal hemoglobin (Hb F), namely Hb F with Gγ chains having glycine in position 136 and Hb F with Ay chains having alanine in position 136, was studied in blood samples and in cultures of erythroid precursors from blood of patients with different hemoglobinopathies. High pressure liquid chromatography (HPLC) was adapted to allow the separation of the methionyl-containing tryptic peptides GγT-15 and AγT-15 (which include the Gly → Ala polymorphism at position 136) from a digest of microquantities of 35S-methionyl labelled Hb F. This method was sensitive enough to quantitate the relative production of the Gγ and Aγ chains by erythroid colonies derived from cloned Burst Forming Units (BFU-E) which were cultured for 16 days on methylcellulose. The production of Hb F in these colonies was generally higher than the level of Hb F in blood except for subjects with the GγAγ-HPFH heterozygosity. The Gγ to Aγ ratio in the Hb F produced in cultures of cells from Gγδβ-thalassemia ...

Hemoglobinopathies observed in the population of the Southeastern United States (SE-USA).

A survey of nearly 250,000 citizens of Georgia and South Carolina conducted during the past twenty years has led to the detection of over 40 abnormal hemoglobins and several additional hemoglobinopathies. The presence of some of these hemoglobin abnormalities cause (severe) clinical symptoms but others remain undetected unless a specific search is initiated. The incidence of Hb S varies slightly among the populations of different areas, and appears to be the highest in the coastal counties of Georgia and South Carolina. A survey of over 17,000 persons of mainly high school and college age has shown that a significant number of cases with clinically significant hemoglobinopathies will remain undetected unless such surveys are actively promoted.

The Mγ chain of human fetal hemoglobin; its identification and occurrence

Abstract High-performance liquid chromatographic procedures have been used in the detection and identification of a new γ chain of human fetal hemoglobin (Hb). This Mγ chain is characterized by a Leu → Met replacement at position γ141; no other structural variations have been observed. The Mγ chain has been detected in red cell lysates of subjects with a heterozygosity for one of many types of so-called hereditary persistence of fetal hemoglobin conditions, which are characterized by an increased level of HB F in adult life, in sickle cell anemia, and in a few cord blood samples. At present it is not possible to definitely identify the genetic cause of this newly discovered heterogeneity; an infidelity in translation or the existence of an unrecognized γ globin gene should be considered.