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Ashkenazi Jews

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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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Jews, and Ashkenazi Jews in particular, are very genetically distinctive. A short and sweet way to think about this population is that they’re a moderately recent admixture between a Middle Eastern population, and Western Europeans, which has been relatively isolated due to sociocultural forces. As far as their inbreeding, well, here’s one recent paper, Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population: To explore the amount of genetic variation within the AJ and European populations, we first measured the mean heterozygosity. Surprisingly, we found a higher level of heterozygosity among AJ individuals compared with Europeans…confirming speculation made in one recent report and a trend seen in another…Although this difference may appear small, it is highly statistically significant because of the large number of individuals and markers analyzed, even after pruning SNPs that are in high LD. The higher diversity in the AJ population was paralleled by a lower inbreeding coefficient, F, indicating the AJ population is more outbred than Europeans, not inbred, as has long been assumed…The greater genetic variation among the AJ population was further confirmed using a pairwise identity-by-state (IBS) permutation test, which showed that average pairs of AJ individuals have significantly less genome-wide IBS sharing than pairs of EA or Euro individuals…Thus, our results show that the AJ population is more genetically diverse than Europeans. How could Ashkenazi Jews be more diverse? Look at what I wrote above, and what most people intuitively assume: Ashkenazi Jews are an admixed population, so they likely carry the alleles unique to both Western Europeans and Middle Eastern peoples! On the other hand, Ashkenazi Jews do have a lot of the genome identical by descent, as befits a population which has long been endogamous, and entered into a recent population expansion from a more modest base.

Image credit: Georges Beard.

(Republished from Discover/GNXP by permission of author or representative)
 
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Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at http://www.razib.com"