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The proportion of some a chain variants in the peripheral blood of heterozygotes has been a most useful marker for the number and activity of the a chain genes of human hemoglobin. Among these, Hb G-Philadelphia(or α2 68Lys β2) has been found in association with a heterozygous or a homozygous α-thal-2, a β-thal trait (AGAβTH) or a Hb S heterozygosity (ASAG) and a Hb S homozygosity (SSG). Hb G-Philadelphia heterozygotes differ in the proporticn of Hb G, MCV and MCH values and Σα/non-α biosynthetic ratios. Two categories have been noted in our laboratories among adult heterozygotes., peer-reviewed more...

Patients with Sickle Cell Anemia (SS) associated with homozygous α-thalassemia-2 (-α/-α; βs/βs) are difficult to detect because the in vitro synthesis of hemoglobin chains may be balanced after prolonged incubation (>120 min). However, a distinct imbalance can be present at early incubation times. We studied chain synthesis on whole cell globin at 10, 30, and 120 min incubation in 38 SS and 4 S/β°-thal patients and compared the data with hematological observations., peer-reviewed more...

Approximately 40% of more than 100 young Hb S homozygotes attending the Pediatric Clinic of the Comprehensive Sickle Cell Center of the Medical College of Georgia in Augusta have an associated α-thalassemia-2 (α-thal-2) heteroztgosity, i.e. the -α/-α; βs/βs condition, or homozygosity, i.e. the -α/-α; βs/βs condition. These conditions are documented by pulse incubations of peripheral blood reticulocytes and by gene mapping using recombinant DNA probes. All α-thal-2 deletions are associated with a 16 Kb Bgl II α chain DNA fragment which arises from a deletion of the 3' end of the α2 gene, the 5' end of the α1 gene and includes the intergenic DNA. Fusion of the residual 3' and 5' ends of the α2 and α1 genes results in a single active a chain gene, i.e. the -3.7 Kb or Rightward type of deletion. Its 3' sequences belong to the α1 gene. The homozygosity for the condition and Hb S is characterized by higher Hb levels without an accompanying increase of Hb F percentages; a distinct microcytosis and hypochromia; splenomegaly and decreased α/non-α values., peer-reviewed more...

A number of deletions have been documented among the non-α globin genes of man that are associated with repression of residual 3' genes. Opportunities to pursue similar structure function correlations among the α and ζ globin genes have been less frequent. The most common deletion observed has been that of one of the two a globin genes in cis on chromosome 16 due to the -3.7 type of α-Thal-2. It is found in 33% of 345 Black children in the Pediatric Sickle Cell Clinics of our center. The same α-Thal as semi a-2 condition has been documented by gene mapping or family studies or both among 48 newborn and adult Hb G Philadelphia (Hb G) heterozygotes from the Black population of the Southeastern USA and Caucasians from Northern Italy. Hb G is rather unique among hemoglobin variants because it has been observed in association with a diversity of a globin genotypes having 3, 2, 1 or O additional αA globin genes in cis or in trans to the αG gene. Quantification of the αG globin produced from each α6 globin qene in probands with the ααG/αα, -αG/αα, -αG/-α, -αG/-αG and -αG/-- genotypes show that there is considerable derepression of the αG globin gene in cis to the -3.7 α-Thal-2 deletion and of the αA genes in trans., peer-reviewed more...

DNA samples from 345 Black children, aged 0-18 years with SS, SC and Sβ+Thal were tested with restriction endonucleases and α or ζ globin DNA probes. A -3.7 kb type of α-Thal-2 (or -α/) was found in 34% with -α/αα and 4% with -α/-α (gene frequency= 0.20). None had the -4.2 kb type of α-Thal-2. The incidence of a-Thal-2 was the same among SS, SC and Sβ+Thal patients., peer-reviewed more...