The principles of human biochemical genetics / Harry Harris.

  • Harry Harris
Date:
1970
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: The principles of human biochemical genetics / Harry Harris. Source: Wellcome Collection.

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    The haemoglobin variants 5 tory functions are still however very obscure, and so far no satisfactory general theory, at least for multicellular organisms, has as yet been devel¬ oped (see ch. 4, p, 90). Nevertheless, one can say that the enzyme and protein makeup of each individual must in a very direct sense be a reflexion of his genetical constitution. Furthermore, one may anticipate that inherited differences between individual members of the species, whether they are expressed as differences in normal physical, physiological or mental charac¬ teristics, or as différences in the development of particular abnormalities, are likely to be a consequence of differences in enzyme or protein synthesis. 1.2. The haemoglobin variants The first direct evidence that a gene mutation can result in the synthesis of an altered protein came from work on haemoglobin in the condition called sickle-cell disease or sickle-cell anaemia. It has been known for many years that the red blood cells of certain individuals have the peculiar property of undergoing reversible alterations in shape when subjected to changes in the partial pressure of oxygen (Herrick 1910, Hahn and Gillespie 1927). When oxygenated, the cells are biconcave discs like the red cells of normal individuals. However, when they are deoxygenated, they become elongated, filamentous and sickle-shaped. Most people whose red cells show the so-called 'sickling phenomenon' are quite healthy. They are said to have the sickle-cell trait. In some individuals, however, 'sickling' is associated with a severe and characteristic form of anaemia, which is commonly fatal in childhood or adolescence. This con¬ dition is usually called sickle-cell disease. The sickling phenomenon is common in Central Africa where in many areas 20 % or more of the popu¬ lation may have the sickle-cell trait, and a significant fraction of individuals (1-2%) may be expected to die of sickle-cell anaemia in early life. It is also found not infrequently among Negro populations hving in other parts of the world, such as the U.S.A. But it is rare or absent in most other human populations. The pecuHarity is an inherited characteristic, and in 1949 Neel and Beet working independently showed that the pedigrees could be most simply explained by the hypothesis that individuals with the sickle-cell trait and those with sickle-cell anaemia are respectively heterozygous and homozygous for a particular abnormal gene located on one of the autosomal chromosomes. Thus individuals who receive the abnormal gene from one parent but its normal allele from the other would be expected to have the sickle-cell trait.