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April 04, 2004

"An intriguing mystery"

On the road I've been re-reading a copy of Principles of Population Genetics by Daniel Hartl & Andrew Clark (2nd edition, 1989). A box on page 324-325 (chapter on "Population Subdivision & Migration") has the following:


Four Israeli communities characterized by large families & high levels of consanguinity were found to display four different lysosomal storage disorders. The coincidence of four distinct diseases with similar biochemical consequences is quite extraordinary...The four disorders - including Tay Sachs, Gaucher, Niemann-Pick, and mucolipidosis IV - are genetically distinct, but all four are characterized by an excess of a type of lipid known as sphingolipid, and all involve sphingolipids with a ceramid-lipid backgound...Although it is not useful to perform a formal statistical test on this observation, it does suggest that the clustering of such similar diseases would not be likely to occur by chance alone. There has been a suggestion that the prevalence of lysosomal storage diseases in these populations may be the result of natural selection, perhaps favoring carriers of the diseases in some as yet undisclosed manner. One speculation is that resistance to tuberculosis and pneumonia is involved. However, the cause of the clustering of these otherwise rare diseases remains an intriguing mystery.

Here are selections from a recent paper (full text at the link) from the authors cited by Hartl & Clark.

Regarding Ashkenazi Jews, although we have no clear evidence for the selection force, we can safely assume that the environmental factor lasted for centuries and that there is no reason to doubt that this selection force was effective in Central Europe as well as in the eastern part. Medical care for the Jewish people was not basically different in these regions. Thus, we would expect to find diverse distributions of allelic mutations for a selection process. Although the four LSDs are recessive, it can be postulated that, under extreme conditions, such as lung disorders, heterozygotes might undergo even a slight lysosomal storage of these substances, which might confer beneficial resistance to these conditions.
...
One may wonder why the selection phenomenon was restricted primarily to the Ashkenazim and not to the non-Jewish people around them. Two, equally plausible, assumptions might explain this phenomenon. (a) The Jews in Europe, particularly in earlier periods (i.e., the 10th-17th centuries) lived for the most part in an extremely poor socioeconomic status with poor medical management. Thus, a selection force by heterozygous advantage might have been more effective for that population. (b) The genetic background of Jews was shown to be unique and different from that of other European people. It can be postulated that this particular genetic structure might have conferred a higher sensitivity or susceptibility to certain lung disorders, when compared with other people in the same region.
Welll, as regular readers of GNXP are aware, I know some folks who agree with the selection pressure part, but disagree on the specifics, with the above authors. When Greg & Henry have their paper published, we can compare the plausibility of their thesis with the one above (I am unconvinced by Risch's argument for genetic drift). One thing for sure though, their assertions are in much bolder face and more baldly stated.
Posted by razib at 09:03 AM