Human biochemical genetics / by H. Harris.

  • Harris, Harry, 1919-1994.
Date:
1966
Catalogue details

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

Credit: Human biochemical genetics / by H. Harris. Source: Wellcome Collection.

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    HETEROZYGOTES AND HOMOZYGOTES 25 to cope with normal metabolic requirements and no ill-effects ensue. Thus the mental defect and the phenylpyruvic acid excretion could be regarded as 'recessive' characters, and the fasting plasma phenyl¬ alanine levels and the response to the phenylalanine tolerance test as 'incompletely recessive' characters. The differences, however, are essentially reflections of the amount of the specific enzyme activity present in the livers of the two kinds of individuals. This in turn depends on whether the abnormal gene is present in single or double dose, or perhaps more correctly in this case on whether the normal allele is present in single dose or not at aU. At this level of analysis the terms dominance and recessivity are not very useful. Another interesting example of the same sort of thing is provided by one of the types of classical cystinuria. The homozygotes excrete grossly abnormal quantities of cystine, lysine, arginine and ornithine in their urine. The heterozygotes excrete moderately increased quanti¬ ties of cystine and lysine, but the excretion of arginine and probably also of ornithine are not usually elevated. Thus, if one only had available a method for determining arginine in urine, the peculiarity would appear to be completely recessive. If, however, one can esti¬ mate cystine or lysine, a different picture emerges. In fact, the abnormal excretion of these four aminoacids appears to depend on a specific defect in renal tubular reabsorption, and the relative quantities excreted in the heterozygotes and the homozygotes on the degree of this abnormahty. The same principle is illustrated by the findings in the sickle-cell trait and in sickle-cell anaemia, which occur respectively in individuals heterozygous and homozygous for a single abnormal gene. The sickling phenomenon, that is the characteristic alteration of shape of the erythrocytes on deoxygenation, is found in both heterozygotes and homozygotes. Anaemia occurs only in the homozygotes. Thus the former might be regarded as a dominant character and the latter as a recessive one. The reason for these differences is that while most of the haemoglobin formed in the homozygote is of the abnormal or sickle-cell type, less than half of the haemoglobin formed in the heterozygotes is of this kind. There is enough sickle-cell haemoglobin synthesised in both heterozygotes and homozygotes to cause the sickling phenomenon, but only in the homozygotes is the disturbance sufficiently great to result in chronic haemolytic anaemia. In general it appears that, while the terms dominance and re¬ cessivity may be useful descriptively, the important problem with 3 HB