![]() The efforts of the last 30 to 40 years to understand the mechanisms that control hemoglobin switching have been influenced by the appreciation that this phenomenon is not only biologically interesting but also relevant to development of treatments and eventually a cure for thalassemia and sickle cell disease. It became obvious then that abundant synthesis of fetal hemoglobin can cure β thalassemia and sickle cell disease. From various genetic and biochemical studies it was then realized that the production of fetal hemoglobin is the reason patients with severe β chain deficiency remain alive. Many biochemical analyses of the hemoglobin of these patients followed and for about 15 years the presence of fetal hemoglobin in this condition remained a puzzle there were even articles claiming that Cooley's anemia is due to abnormal fetal hemoglobin! The pathophysiological role of fetal hemoglobin in thalassemia was finally delineated in the early 1960s. That the patients with Cooley's anemia (severe β thalassemia) have alkaline-resistant, i.e., fetal hemoglobin, was first discovered by Italian hematologists in 1943. Shown below is an example of a Serial Cloner file viewed with the original program and with SnapGene. The role of fetal hemoglobin in thalassemia was more difficult to understand. SnapGene and SnapGene Viewer can read files created by Serial Cloner. The fact that fetal hemoglobin ameliorates the severity of sickle cell disease was appreciated in the late 1940s and the 1950s. The medical relevance of hemoglobin switching became apparent before any systematic experimentation started. Systematic mechanistic research was initiated in the 1970s with the introduction of hemopoietic cell cultures and recombinant DNA methods in the investigation of the phenomenon. Beta-globin is a component (subunit) of a larger protein called hemoglobin, which is located inside red blood cells. Its underlying mutation creates an abnormal splice acceptor site in the HBB gene, and while partially retaining normal splicing of HBB, it severely. In the 1950s and 1960s, research on hemoglobin switching was essentially based on description of hemoglobin phenotypes. In the 1950s and 1960s, various mutations that result in continuation of fetal hemoglobin in the adult (hereditary persistence of fetal hemoglobin) were characterized. Switches in hemoglobin during development of humans and several animals were characterized in detail in the 1950s, when simple electrophoretic methods were introduced for hemoglobin analysis. Orkin and I decided he should clone these beta globin genes and sequence. Differences in oxygen affinity between embryonic and adult blood were discovered in the beginning of the 20th century, while the first physical evidence that embryonic hemoglobin differs from adult hemoglobin was obtained in the 1930s. Hemoglobin A makes up 98 of the hemoglobin in adult red cells and is composed. ![]() The first evidence for developmental changes in hemoglobin was obtained late in the 19th century when it was found that the hemoglobin of the newborn is alkali-resistant, while hemoglobin of the adult is alkali-sensitive.
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