Once upon a time, prominent geneticists put forth the notion that a given common disease was probably caused by a very limited number of alleles. If so, that would have made life easier: testing and drug development would have been simpler. The argument was that the number of alleles at every locus should have been low way back in prehistory, since the effective population back then seems to have been small. This model assumed that most of the common diseases under consideration had little selective impact.
A paper by David Reich and Eric Lander (On the Allelic Spectrum of Human Disease) discussed this about ten years ago. They gave a number of examples of genetic diseases that are caused by one or a few alleles ( at least in some populations). They mentioned cystic fibrosis, Gaucher and Tay-Sachs disease (both common in Ashkenazi Jews, both affecting the same enzyme path, both stimulate neuron growth…), Wilson’s disease (in Sardinia), hemochromatosis, and beta-thalassemia.
The problem is that at least three of their examples (CF, hemochromatosis, and beta-thalassemia) and probably five (Gaucher and Tay-Sachs too) are common because they confer selective advantage in heterozygotes. Of course that makes sense: why would an allele whose main effect is deleterious ever be common?
The case in which such a simple allelic spectrum seems most likely (not counting strong heterozygote advantage) would be a disease that strikes in old age. The reduction in fitness caused by an allele that messes you up at 85 is naturally small: it could easily be balanced by a teeny selective advantage earlier in life, and drift might be stronger than selection, allowing a weakly deleterious allele to reach high frequency.
The successes of this approach have been few: most have been in diseases of old age, such as Alzheimer’s, macular degeneration, and exfoliation glaucoma.
In general the common disease-common variant strategy has been a bust, enough so that it’s hard to find anyone who admits to ever having believed in it. I think many people who argued in favor of it did believe, though. I don’t think they lied for funding, although admittedly the prospect of serious funding does tend to cloud men’s minds. I remember Kari Stefansson reacting with surprise to his group’s finding that schizophrenia seems to be caused by many rare risk alleles, different ones in every family: “I would have thought the brain was a luxury organ when it comes to reproductive success. ” I think that the general feeling in the human genetics community at that time was that natural selection doesn’t really happen in humans. Which is screwy as hell, but there it is.
Why would they have thought this? My best guess is a combination of factors, not the same mix in every individual: dislike of some implications of continuing natural selection in humans, misunderstood neutral theory, confused ideas received from anthropologists about how culture trumped selection, very limited educational exposure to evolutionary genetics, and mutational pressure.
Addendum: If David Reich ever had wrong ideas about human evolution, he got over it. He’s quality.