The founder effect and deleterious genes.

During the rapid growth of a population from a few founders, a single deleterious gene in a founder can attain an appreciable frequency in later generations. A computer simulation, which has the population double itself in early generations, indicates a lethal could attain a frequency of 0.1. Since deleterious recessive genes are eliminated from large populations at a very slow rate, variations in their frequencies in present major human populations may be due to the founder effect during earlier rapid expansion. Many distinctive human populations are characterized by the presence of one or more lethal or severely deleterious genes in frequencies which would be defined as polymorphic according to Ford's ('40) famous definition. The particular genetic disorder, however, varies. The Old Order Amish of Lancaster County, Pennsylvania have a gene frequency of 0.07 for the recessive Ellis-van Creveld syndrome, while the Amish as a whole have a frequency of about 0.05 of the recessive cartilage-hair hypoplasia syndrome ( McKusick et al., '64). Many of the tri-racial isolates of Eastern United States also have a high frequency of a deleterious gene (Witkop et al., '66). Although such populations are frequently defined by religious or ethnic criteria, there are others not so defined. Several island populations in the Nand archipelago have a gene frequency of greater than 0.1 for von Willebrand's disease (Eriksson, '61), and the Boer population of South Africa and some populations of Northern Sweden have frequencies of porphyria much greater than those of other populations (Dean, '63; Waldenstrom and Haeger-Aronsen, '67). However, these conditions are dominant and do not have the very severe effects of other hereditary disorders found in high frequencies. On the other hand the population of the Chicoutimi District of Quebec has recently been found to have a gene frequency of about 0.02 for tyrosinemia, which is a lethal recessive (Laberge and Dallaire, '67). In most of these cases the population in question has undergone a rapid increase in recent years, and the question arises as to whether this rapid expansion and the AM. J. PHYS. ANTXROP., 30: 55-60. original small size of the isolate could account for the high frequency of the deleterious gene. Such an explanation by the founder effect seems obviously to apply to most of the cases cited above, but the founder effect may well be a more general explanation of human gene frequency differences. It is now becoming apparent that the major populations of mankind vary significantly in their frequencies of deleterious genes and that many large populations such as Eastern European Jews have high frequencies of deleterious genes which are found in low frequencies in other populations (McKusick, '66). There have been many attempts to determine how such genes could be polymorphic, for example, Anderson et al. ('67) and Knudson et al. ('67) have discussed cystic fibrosis and Myrianthopoulos and Aronson ( '66), TaySachs disease. The purpose of this paper js to attempt to determine the extent to which the founder effect can cause high frequencies of deleterious genes with various models of population expansion. The occurrence which initiated this research is the gene for sickle cell hemoglobin in the Brandywine isolate of Southeast Maryland. At present the sickle cell gene frequency in this isolate is about 0.1 (Rucknagel, '64). The high frequencies of this gene in many parts of Africa, India, and the Middle East are now well-accepted as being due to a relative resistance of the sickle cell heterozygote to falciparum malaria. The high frequency in the Brandywine isolate may have a similar explanation, but the surrounding Negro population does not have such a high frequency. And although the endemicity of falciparum