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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    30 ASPECTS OF MENDELIAN HEREDITY first type involves a balance between mutation and selection, and the second type involves a fitness differential such that heterozygotes are at some advantage compared with homozygotes. The latter situation can be referred to as 'balanced polymorphism'. Both types of situations represent stable equilibria. Provided the conditions remain the same, the system tends to revert to its original state following any disturbances of gene frequency of a chance or fortuitous character. Both of these forms of equilibria are probably important in deter¬ mining the incidence of different inherited diseases and other inborn pecuHarities in human populations. The occurrence of a mutation of a 'normal' gene to its abnormal allele will tend to offset the loss of the abnormal gene due to natural selection. At a certain point one could expect an equiHbrium to be set up in which the loss of the gene, due to the reduced fitness of those genotypes in which it produces deleterious consequences, is balanced by the occurrence of fresh mutations. Once such an equilibrium point has been reached the frequency of the gene, and the incidence of the abnormality which it causes will tend to remain the same in successive generations. The prevalence of the abnormality will be determined by the fitness of the affected individuals, and the mutation rate of the gene in question. For example, in the case of a rare sex-linked recessive condition such as haemophilia an equilibrium would be expected when /^ = 4(1 -/) where ¡i = the rate of mutation of the normal gene H to the haemo- philic gene h, per chromosome per generation. q = the gene frequency of h. In this case the frequency of haemophilia in all male children at birth, and / = the fitness of haemophilics. That is the mean number of progeny of all haemophihcs born compared with the number of progeny of other members of the population. The factor ^ is introduced because for every haemophilic gene in males there are two in heterozygous females, and selection only acts against the affected individuals. Haldane (6), using the data obtained in an extensive survey of haemo¬ philia in Denmark by Andreasen, estimated that the frequency of haemophilia in all males at birth was about 13 in every 100,000, and that their biological fitness was about 0-28 of that of normal people. He concluded that if the haemophiUc gene was being held in equi-