Mutated genes (of any kind) continually enter the human gene pool (i.e. human reproductive cells) and affect future offspring. Some mutations have no noticeable effect, some have a benign effect (e.g. attached ear-lobes), while others are so severe that the child dies shortly after conception.
If a mutation weakens the individual, in particular if it makes them unable or less likely to reproduce, the mutated gene drops from the gene pool, and the mutation is called harmful. Similarly any mutation that makes an individual more likely to reproduce accumulates in the gene pool and is called beneficial.
We will restrict ourselves to harmful mutations and consider only the so-called recessive genes, which have a noticeable effect only when both copies of this gene (one from each parent) have the mutation.
Suppose a harmful recessive gene enters the human gene pool, by mutation. The gene will pass through future generations until eventually some individual inherits two copies of that gene, and dies before reproducing.
If the gene spreads randomly though the population, with say one individual in N carrying a copy, then on average, once in N×N times will both members of a couple carry this gene, and once in 4 times will their offspring inherit both copies. i.e. one of 4×N×N births will inherit both genes and remove them from the pool.
If a population has an abnormally high incidence of the gene, the genes will leave at a faster rate than they appear, while in a population with abnormally low incidence the genes will leave at a slower rate than they appear. Either way, eventually the gene pool will reach an equilibrium with the harmful genes leaving at the same rate as they enter.
A mutation in a gene that affects the valves that allow certain substances to pass through human cell walls causes the congenital disease CF. If this process fails, some cells cannot absorb or excrete as much water as they should, resulting in overly viscous bodily fluids (e.g. in the intestines and lungs) that eventually kill the individual.
Should only one of an individual's two CF genes not function properly, half of the the person's cell valves will do twice the usual work, the cells will function normally, and the individual will not even know they have this damaged gene.
Among people of European descent, about one in 2500 births results in an individual with CF. Using the inheritance formula given above, that means that 2500 = 4×N×N, which means that N = 25. i.e. one person in 25 carries the CF gene.
Now that is a very high occurrence rate. Huntington's Disease for instance is far more rare even though its often not being diagnosed until after an individual has had children means that it leaves the gene pool at a much slower rate than CF.
This poses one very large question: why is the incidence of CF so high among Europeans? What event happened that the CF gene carriers still haven't recovered from it?
Perhaps in times past, CF victims were somehow able to live longer lives, long enough in fact to have children of their own. Could some special diet or medicine, knowledge of which we have now lost, have kept these people alive? This seems very unlikely.
Perhaps an isolated group of people experienced a very high rate of mutation (say they lived in a valley that was near large deposits of radioactive ore such as uranium). Eventually they realized that their mutual mating was unhealthy and so left their original home and mixed with the general population, avoiding each other as much as possible in the selection of mates.
One obvious problem with this comes from the complete lack of any historical record of such an event. Yes, groups without a homeland do exist in Europe (e.g. Jews and Gypsies), but they have remained genetically isolated and didn't mix with the general population.
And while other groups have vanished from history (e.g. the Ten Tribes of Israel) and presumably mingled with the general population, this explanation presents even more of a problem. Had the mixing occurred relatively recently, the group would have to comprise 4% of the population. And the effect of the loss of the gene from the gene pool means that the further back in time one considers, the larger the group required.
Perhaps the situation dates back to the origins of the entire European race, with whatever caused the race to exist giving them a very high rate of the CF gene to start with.
But again the current declining incidence means an increasing incidence as one goes back in time, and one can't go back thousands of years without increasing the rate to over 100%, making the whole thing impossible.
But perhaps the rate doesn't decline as rapidly as we think it does. How much confidence do we have in this?
One old-wives tale says that if you kiss a baby and find it salty you know that the baby will have a miserable life. Well CF children happen to have very salty sweat, so that could explain the origin of this idea.
But how many babies would the old wifes have had to kiss to realize the connection? At the current rate of 1 birth in 2500, it seems very unlikely that any old European town or village would have many cases, and even less likely that anyone would have kissed enough such babies to have made the connection.
So, if that is the origin of this tale, the incidence rate really must have been far higher then than it is now.
It appears that at some time, hundreds of years ago, the incidence of CF increased to a very high level in Europe and has been declining ever since. We have just considered, without much success, what might have increased the number of affected people. But perhaps the number of affected people didn't increase.
The incidence rate is not only affected by the number of people that carry the gene, but also by the number of people that don't. Suppose instead of increasing the CF gene carriers in the population, something happened to decrease the part of the population that wasn't carrying the gene. Such a situation would require that the CF gene behave beneficially, allowing the carriers to reproduce while the non-carriers failed.
One obvious event, and perhaps the only possible one, occurred a thousand years ago when plague swept through Europe, killing a third of the population. If we suppose that for some reason CF carriers were immune to the disease (perhaps the malformed valves are perfect for trapping plague bacteria), could that account for the current situation?
Unfortunately not. Even with a loss of a third of the non-carrying population, the percentage of CF carriers wouldn't have gone up by nearly enough to explain the current rate (e.g. rather than one in a million it would increase to one and a half in a million).
If the plague kills people in the general population, it can almost certainly kill unborn children. Many mothers must have sickened and recovered from the plague but miscarried as a result. Such deaths would not have been counted in the death toll.
And perhaps, and here comes the big perhaps, women infected with but not killed by the plague, would carry it for years, unable to bear any further children.
The story of the Pied Piper comes from the loss of life during the Plague. But maybe the story contains more realism than people thought. Perhaps rather than an exaggeration of the massive loss (young children having more susceptibility to disease than adults) the almost total loss of children was real and lasted for a long time.
In such a situation, almost no new children would appear, but in each village there would be a small number of unaffected families. In such families, either the mother or father carries the CF gene and so half of their conceptions would not fall victim to the plague. In addition, a small number of couples would both carry the gene and a quarter of their children would inherit the disease (the Pied Piper left one crippled child behind).
To go further, in such a world, wouldn't a wife with a healthy family want to help her barren sisters? Might she not loan her husband to them for that purpose? In half of such cases, he would carry the gene, and the loan would be successful.
Might this not extend to cousins too, and perhaps close friends, or even those not so close?
The Roman Church, which dominated European life during these times, certainly wouldn't approve of such adulterous practices, so none of this would happen openly or appear as part of the history of the times (very few people outside of the Church hierarchy could write).
If for a generation or two, most babies in Europe had a father that carried the CF gene, that would certainly explain its currently high incidence.
The above was written several years ago. Research in 2007 suggests that the real cause of the high incidence of CF is that the gene lessens the effects of cholera, a disease that kills by causing massive fluid loss (diarrhea). Victims with two CF genes are effectively immune. Victims with one CF gene have the disease with half the severity and so are more likely to survive. Large outbreaks of cholera are likely to kill a higher proportion of non-CF carriers, thus ensuring a higher concentration of CF genes in the surviving population.