Tuesday 31 March 2015


Tay-Sachs is a terrible degenerative disease that starts to affect children just as they start to crawl and finishes them off before they are ready for primary school.  I mention it in passing early on in my course about Human Physiology because it is to do with a dysfunction in lyzosomes which are little blobs (membrane-bound vesicles, indeed) inside most of the cells of your body which act as waste-processing factories.  One of these clean-up processes requires an enzyme called hexosaminidase A which breaks down fatty molecules called gangliosides.  In the developing brain there is an enormous amount of metabolic activity: neurons are made, novel connections are set up and there is a huge amount of turn over of the bit-and-bobs that make up the cells.  If you can't break down the gangliosides they accumulate and eventually destroy the function of the neurons in which they build up.. You can't break down the gangliosides if you have inherited two defective copies of the gene for Hexosaminidase A: one from each of your parents. If you have one blitzed copy and one functional copy of the gene then you're fine and there are a lot of these "carriers" out there.

Of course it depends what you mean by "a lot"; there are about 1 million carriers in the USA out of a total population of 300 million, so if you pick you partner at random and you are yourself a carrier there is a 1:300 chance that any of your children will be affected.  The odds are still stacked in your favour because 3 out of 4 of your offspring will not develop the dread disease.  You could, of course, be unlucky and have four affected children in a row.  If you don't know what your Tay-Sachs status is, the odds are better still = 1/300 * 1/300 * 1/4 = 1:360,000 lives births in the USA develop this infantile Tay-Sachs.

But some groups in the great melting pot are much more likely to have children with Tay-Sachs because the frequency of carriers is much higher: by accident; by cultural endogamy [a tendency to fall for the girl next door]; or good old inbreeding.  Incest, they say, is the game the whole family can play. Notably, the Ashkenazim have higher frequencies of Tay-Sachs carriers [1/30], as do some groups of Québécois and their cousins the Cajuns of Louisiana and even Irish-Americans.  Here the odds of having a T-S child = 1/30 * 1/30 * 1/4 = 1:3,600 or a hundred times more likely than in the general population.  Despite the manifest increase in social capital from such schemes as The Jack and Jill Foundation, it is a hard road to care for a deeply handicapped child and most people would prefer to avoid that cross.

The Ashkenazim have developed a clever system for minimising the chances of their community bringing Tay-Sachs children into this world.  Dor Yeshorim (דור ישרים‎) - "upright generation" aka Committee for Prevention of Jewish Genetic Diseases was set up a generation ago in the 1980s by a rabbi in NYC.  One of the neat things about the scheme is that it is anonymous and so can't be used to hike up your health insurance premiums or deny employment.  On a regular basis, Dor Yeshorim goes to Jewish schools and takes DNA samples in exchange for a docket containing a PIN code.  The DNA is processed to identify carriers, not only of Tay-Sachs, but also Cystic Fibrosis and maybe a dozen other potentialy damaging genetic traits but these data stay on the computer until a Jewish boy and a Jewish girl think they might take the plunge together.  In some of those communities, they practice a system of arranged marriages called Shidduch (שִׁדּוּךְ‎) in which the families get together and decide that Moshe and Rebecca might be a good match.  Over a few meetings the eager elders gradually fade discretely into the back-ground and the boy and girl get to talk to each other and start to imagine what living together might entail.  At some stage (earlier the better), they submit their PIN numbers to Dor Yeshorim and the computer says Yes or less likely No.  This cunning plan has been remarkably effective in reducing the incidence of the disease in that community but has had no effect whatsoever on the prevalence of carriers in the population.

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