Blood, 1955, Vol. 10, No. 4, pp. 341-350.
© 1955 American Society of Hematology, Inc.
Evidence Concerning the Inadequacy of Mutation as an
Explanation of the Frequency of the Sickle Cell
Gene in the Belgian Congo
J. M. VANDEPITTE 1,
WOLF W. ZUELZER 1,
JAMES V. NEEL 1, and
J. COLAERT 1
1 Medical Laboratory, Institute of Tropical Medicine, Léopoldville, Belgian
Congo; the Children’s Hospital of Michigan, Detroit, Michigan; the Institute of Human
Biology, University of Michigan, Ann Arbor, Michigan; and the Government Hospital,
Léopoldville, Belgian Congo.
It is pointed out that there are two outstanding (and not mutually exclusive)
possible explanations for the persistence of the sickle cell gene in the face of
strong negative natural selection. These are (1) "balanced polymorphism," and
(2) a high spontaneous mutation rate.
In Léopoldville, Belgian Congo, approximately 25 per cent of the natives
exhibit the sickling phenomenon. Over a two and one-half year period 261 patients with sickle cell disease, distributed among 243 families, were seen at the
Institute of Tropical Medicine in Léopoldville. A total of 233 of the 243 mothers
of the patients in this series was tested for the sickling phenomenon. Only two
failed to sickle. Hemoglobin from these two women was normal on paper electrophoresis.
The occurrence of these two exceptional mothers can be explained on the basis
of mutation at some stage of oogenesis resulting in a sickle cell gene. Alternate
possible explanations include (1) transmission by the mother of some other abnormal gene affecting hemoglobin synthesis, (2) occurrence in the mother of a
genetic modifier of the effects of the sickle cell gene, (or its normal allele), and (3)
unreported adoption.
These data make possible a preliminary calculation of the extent to which
mutation may be responsible for maintaining the sickle cell gene. Calculations
based on the assumption that both these exceptional mothers indicate the occurrence of a mutation will lead to maximal estimates of the rate of mutation
of the sickle cell gene. This maximal estimate is 1.7 x 10-3 per gene per generation. This rate, although very high by the usual standards of human mutation
rates, is only approximately one-tenth that necessary to offset natural selection
in a population with 25 per cent sickling.
Submitted on June 11, 1954
Accepted on August 15, 1954
