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Ashkenazi Jews Are Not Inbred - 2
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I know I excoriate readers of this weblog for being stupid, ignorant, or lazy. But this constant badgering does result in genuinely insightful and important comments precisely and carefully stated on occasion. I put up my previous post in haste, and when I published it I wasn’t totally happy with the evidence from which the authors adduced that Ashkenazi Jews were not inbred. Here’s why, from the comments: Doesn’t identity-by-state permutations test reflect a counterbalance of admixture vs. inbredness + drift? Rather than just the degree of inbreeding? Since the population has strong admixture effects, a low IBS doesn’t exclude strong inbreeding, does it?

From my little personal experience IBS is not the best statistic from which to generalize widely, and can be highly misleading in admixed individuals, as implied by the commenter. First, since I’ve stated above that the Ashkenazi Jews are admixed, let me go into a tangent as to why Ashkenazi are admixed between a Middle Eastern and Western European population, as opposed to being a relatively unadmixed ancient Eastern Mediterranean group with affinities to both regions. The previous previous paper found evidence of linkage disequilibrium decay. This means that LD was high in admixed individuals in the past, and declined over time. Why?

Imagine someone who is half black and half white. There are particular alleles which are highly diagnostic for black or white ancestry (e.g., SLC24A5 or Duffy). In admixed individuals these alleles will be correlated on the same chromosomal segment from one parent. They will have linear blocks of ancestry; colloquially, one chromosomal pair will be from one population and the other from the other population. Now imagine that you have a population of individuals who are mixed in white and black ancestry, and they pair off with each other over the generations exclusively. The ancestral fractions will remain roughly the same (let’s assume a large effective population), but the genomic segments of ancestry from a specific population will be broken apart by recombination. The more generations from the initial admixture event, the more the blocks of ancestral segments will be scrambled. LD is a statistic which can measure this, since we’re talking about patterns of correlated alleles across loci. Given a long enough time LD will converge upon what you would expected in a random mating population. But if the admixture event was recent enough, then LD will be elevated over intervals which can give you a sense of the time in the past that the admixture event occurred. Ashkenazi Jews exhibit an LD pattern of a population which went through admixture between Europeans and Middle Easterners, not just a population whose allele frequencies lay between these two groups.

With that about the way, how about inbreeding? I will put up a follow up posting on what I mean by inbreeding, but here is a paper which gives a better sense of what’s going on with Ashkenazi Jews, Abraham’s Children in the Genome Era – Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry:

IBD between Jewish individuals exhibited high frequencies of shared segments…The median pair of individuals within a community shared a total of 50 cM IBD (quartiles: 23.0 cM and 92.6 cM)—such levels are expected to be shared by 4th or 5th cousins in a completely outbred population. However, the typical shared segments in these communities were shorter than expected between 5th cousins (8.33 cM length), suggesting multiple lineages of more remote relatedness between most pairs of Jewish individuals….

Within the different Jewish communities, three distinct patterns were observed…The Greek and Turkish Jews had relatively modest levels of IBD, similar to that observed in the French HGDP samples. The Italian, Syrian, Iranian, and Iraqi Jews demonstrated the high levels of IBD that would be expected for extremely inbred populations. Unlike the other populations, the Ashkenazi Jews exhibited increased sharing of segments at the shorter end of the range (i.e., 5 cM length), but decreased sharing at the longer end (i.e., 10 cM)….

Another paper, Fine-scale population structure and the era of next-generation sequencing:

The amount of genomic sharing can be easily quantified and the degree of relationships between a random pair of individuals in a population can be estimated. For example, a random pair of individuals in the Ashkenazi Jewish population are as genetically similar, on average, as fourth cousins…indicating that recent genealogy may be of importance. The impact of inbreeding on the frequency of rare diseases has been demonstrated in historically endogamous populations, such as the Ashkenazim, Hutterites and some island groups…However, if many geographic regions throughout the world are finely structured as suggested by identical-by-descent (IBD) analysis, then populations in those regions may also have elevated rates of rare alleles and correspondingly of unique rare diseases. Indeed, in terms of the average amount of genomic segments’ IBD, the Ashkenazim are not outliers in the global sample mentioned above.

As indicated by the paper by Ralph et. al. many European populations share IBD tracts indicating a fair amount of relatedness on the time scale of ~2,000 years. The Ashkenazi Jewish pattern of lots of short tracts is why services like 23andMe yield so many “relative” matches for individuals of that background. These people share a lot of the same ancestors, but these are often rather far back in time. So, when considering “inbred” as in the products of frequency cousin marriages, Ashkenazi Jews are not inbred in that manner. They don’t exhibit an abnormal level of very long IBD tracts, which is what you get floating around in the population with there are lots of extremely recent common ancestors between one’s two parents. The coefficient of relationship between parents and children is 50%. Between first cousins (in an outbred population) is 12.5%. Between fourth cousins it is 0.2%.

Just because Ashkenazi Jews are not inbred by this measure does not mean that they are not relatively genetically homogeneous person to person, and exhibit a great deal of distinctiveness. They do. But as I stated earlier, that distinctiveness is likely due to an ancient phase cosmopolitan admixture, followed a shift toward relatively strict endogamy imposed by their position as a marginalized minority within Islamic and Christian civilization.

(Republished from Discover/GNXP by permission of author or representative)
 
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  1. So are Ashkenazi Jews more Middle Eastern than European or more European than Middle Eastern?

  2. Luke, they fall somewhat in-between the two. My own opinion is that they are closer to European populations than to the Middle East populations.

    http://www.biomedcentral.com/content/pdf/1471-2156-10-80.pdf

    http://www.ncbi.nlm.nih.gov/pubmed/17245410?dopt=Abstract

    http://genomebiology.com/content/pdf/gb-2009-10-1-r7.pdf

  3. #1, is your question a joke? it’s kind of a dumb thing to ask after this post, where i’m addressing a totally different issue. but, i think the question is close to being “not-even-wrong.” the terms “european” and “middle eastern” define two almost arbitrarily defined sets, where there is a lot of variation within them. e.g., if you use “european” as italian, and “middle eastern” as qatari, then i think AJ are more “european.” if you use “european” as lithuanian and “middle eastern” as syrian, then AJ are more “middle eastern.”

    #2, your citations are OK, but a little out of date, even if they are pretty good (yeah, 2008 is now out of date in this field!). probably better

    http://blogs.discovermagazine.com/gnxp/2010/06/genetics-the-jewish-question/
    http://blogs.discovermagazine.com/gnxp/2010/06/genetics-the-jewish-question/

  4. Lauren Bacall (pictured) is first cousin to the current President of Israel, Shimon Peres. (Bacall’s family name at birth was Persky, from which ‘Peres’ is derived.)

  5. Maju says: • Website

    “Ashkenazi Jews exhibit an LD pattern of a population which went through admixture between Europeans and Middle Easterners, not just a population whose allele frequencies lay between these two groups”.

    I do not see why. Have you (or whoever) compared with Cypriots and Turks.? I say because these populations are of the kind “whose allele frequencies lay between these two groups” and incidentally have a genetic signature almost identical to Western Jews (and when Ashkeanzim and Moroccan Jews refuse to behave properly in Admixture, at least with the “less capricious” Sephardites).

    Of course it is possible that Turks and Cypriots also have the signature of peoples “which went through admixture between Europeans and Middle Easterners” (I’d buy that provided the appropriate, old enough, time frame). True that Ashkenazim show some extra European admixture than other Western Jews but that should not be enough to claim what you say.

  6. I do not see why.

    i thought i explained the LD decay method well enough above, but if not:

    http://www.pnas.org/content/107/suppl.2/8954.full
    http://www.genetics.org/content/185/2/611.full

    the cypriots may well be admixed. the turks certainly are, though the pattern will be different from the AJ i bet (the blocks will be clearer since the admixture is with east asians, but less numerous since the quantum is small.

  7. Maju says: • Website

    But in my exercise of comparing Sephardi Jews (I had to discard Ashkenazim because they behaved as inbred: forming a distinct cluster very early on) with other West Asians. It becomes obvious that Jews, Turks and Cypriots share the main component of all them (cyan in this K=6 graph).

    In that exercise, Europeans were intently removed (because neither Atzmon’10 nor Behar’10 suggested they are too important in Jewish genetics, same for Iranians, other Arabs or North Africans) and Jews certainly cluster with Anatolians/Cypriots very tightly no matter the K-depth. They just have slightly more of two “Palestinian” components (yellow and blue) and slightly less of the “Lebanese” green component – but tiny details all in all.

    “the cypriots may well be admixed. the turks certainly are”

    Are they? I mean: where do you get that from? They are clinally transitional but that’s not the same as “admixed”, as recently admixed. If they are admixed we must think of very ancient admixture, IMO.

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