Ashkenazi Jews are extremely inbred

Neurologists are inherently interested in  psychosis, not least because too much dopamine in the form of L-DOPA can trigger it.  I’ve always found it remarkable that dopamine blocking agents (phenothiazines, and most antipsychotics) can attack psychotic thought itself.  This is much more impressive to me than the ability of other drugs (alcohol, coffee, marijuana, cocaine) to affect mood.

So it’s always worthwhile to read another paper about the genetics of schizophrenia, a very hereditary disease.  All the risk factors we’ve found by GWAS (Genome Wide Association Studies) account for at most of 1/3 of genetic risk in schizophrenia.  For details please see https://luysii.wordpress.com/2014/08/24/tolstoy-rides-again-schizophrenia/.

So I was interested in another crack at finding more genetic causes of schizophrenia  [ Neuron 109, 1465–1478, May 5, 2021 ].  As often happens, the most interesting thing in the paper was something totally tangential  to my original interest in it. 

Here it is —   ”  For example, the Ashkenazi Jewish (AJ) population, currently numbering >10 million individuals world- wide, effectively derives from a mere 300 founders 750 years ago ” (Carmi et al., 2014;Nat. Commun. volume 5, 4835.).  

I find this assertion incredible.  But, as explained below, there is pretty good evidence (although subtle and quite technical) that it’s correct.

Ashkenazi Jews are those previously found only in Europe and the Americas, as opposed to Sephardic Jews, previously found only in the mideast and Africa.  Both are now found in Israel.  Ashkenazi Jews were chosen for the study because any deleterious genes producing schizophrenia  present in the original 300 wouldn’t have been washed out by natural selection in just 30 generations in 750 years. 

The Ashkenazim make the inbreeding among French Canadians look like pikers — a population of 2 million derived from a founder population of 9000 people over the next 170 years — for details please see https://luysii.wordpress.com/2019/07/17/the-wages-of-inbreeding/.  Note that neither population tried to inbreed, it’s just that there was no one else geographically available to breed with for the French Canadians, and no one else culturally available for the Ashkenazi’s.  

At least with the French Canadians we have immigration records to tell us how large the founder population was.  How sure are we about the 300 strong founder population of present day Ashkenazi Jews?  We’re not and I’m not even though it was published in a peer reviewed reputable journal.  There is a lot of guesswork in figuring out just how large a genetic bottleneck is.  It all depends on the model used, and I don’t trust models in general.  I’ve seen too many crash and burn. (For details — https://luysii.wordpress.com/2019/03/03/i-mistrust-models-2/)

However, the Neuron paper contains a reference to another paper which provides excellent empiric evidence for a small founder population, (PLoS Genet. 14, e1007329. 2018).  Here’s a direct quote.  It’s quite a mouthful; I’ll try to explain below the quote what the terms mean, because I think many nonscientific types are likely to be interested in the idea that Ashkenazi Jews are that inbred. 

Just skip the paragraph if it’s incomprehensible, go to *** and read the explanatory material, and then read the paragraph again. 

“We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations.”

****

Explanatory material.

Our genetic material (DNA) is made of 4 different compounds A, T, G, C (called nucleotides) which are linked together in chromosomes.  The order is crucial, just as the order of letters in a word is crucial for meaning (consider united and untied).  So how many slots for the nucleotides are there in our genome ? Just 3,200,000,000.  Just as combinations of dots and dashes code for letters in Morse code, combinations of  3 nucleotides code for the 20 amino acids that make up proteins. 

Proteins are big.  For instance, the protein  (beta-globin)mutated in sickle cell anemia contains 146 amino acids, and all it takes to produce the disease is a switch from one amino acid to another at position six.  The other 145 amino acids in the chain are unchanged. So sickle cell beta globin with a change in its nucleotide sequence is an allele (alternate form) of normal beta globin.  

Every population of people contains alleles of every protein.  Some are common (over 5% of the population showing them), but most are rare.The PLoS paper looked at  73,228 alleles of all 20,000 or so proteins that we have in our genome (yes technology now can do these sorts of things) in the general population.  The authors looked at the alleles in the Ashkenazi population which were present at greater than 1/500 (.2%).  Then they looked at the frequency of the same allele in several other non-Ashkenazi population (about 5000 each of non-Finnish Europeans, African Blacks and Latinos), and found that these alleles occurred15 times less frequently (on average).   So Ashkenazi’s have alleles that are lots more common than in other populations.  Actually it’s more than some, because about 1/3 of the alleles they studied are an average of 15 times as common.

What does this mean?  It means that when a small founder population with a rare allele becomes ‘fruitful and multiplies’, the rare allele will multiply right along with it and not be lost by outbreeding (which was certainly true of the Ashkenazis for 600 of the last 750 years).

Now read the paragraph in bold above again. 

This is the evidence that current day Ashkenazi’s come from a very small founder population.  It’s pretty good.  I hope that I’ve made this somewhat comprehensible;  if not, please write a comment.

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Comments

  • Friedel-Crafty  On May 13, 2021 at 10:51 am

    French-Canadians can also carry Tay-Sachs. As amusing as it is to consider the hypothesis of an Ashkenazi voyageur / fur-trader deep in the Quebec hinterlands, the best explanation is that this is, like the Ashkenazim, a case of inbreeding within a small population.
    https://science.sciencemag.org/content/232/4758/1646

    • Mel  On June 4, 2021 at 8:37 am

      This must be deeply culturally embedded as the individuals *agree to forgo testing by any other means.* There’s a big world out there beyond Tay-Sachs… I’m disappointed if my Ashkenazi brethren aren’t participating in the large-scale ancestry and genome-wide association studies underway by the large commercial genetic testing companies.

      Seems strange that a huge group of people, at least many of whom are well-educated and perhaps doctors themselves, would voluntarily blind themselves! But then, looking at responses to covid and vaccination at the community level, maybe not so surprising.

  • Ogamol  On May 17, 2021 at 5:16 pm

    Enlightening. I was unaware of the French Canadian situation. And my Ashkenazi ancestry (50%) is … somewhat enhanced. (In a way akin to the discovery of Ethiopians who are genetic Levites.)

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