Thanks to the efforts of geneticists the story of the extinction of the Spanish Habsburgs is now well known. They are in short a case study in the disastrous consequences of an inbred pedigree. The downsides of inbreeding are to some extent intuitively understood by all, especially consanguineous relations between first order relatives. Though I’m willing to bet that all things equal inbred individuals are not as attractive or intelligent as outbred individuals, the literature in this area for humans is surprisingly thin. A major problem is controlling for confounds; all things are often not equal (e.g., imagine if inbreeding is more common in marginal isolated communities, which is often true in the West. See Consanguinity, Inbreeding, and Genetic Drift in Italy, where it is obvious that the less developed areas of Italy had elevated rates of marriage between relatives despite Catholic discouragement of the practice). But the case that inbreeding results in the expression of deleterious recessive diseases is more straightforward. The rarer the disease, the higher the proportion of individuals who are affected who are the consequence of inbreeding. This is due to the logical fact that very rare alleles tend not to come back together in homozygote form due to the character of the Hardy-Weinberg equilibrium. If the recessive trait is caused by a minor allele with a frequency of p, p2 can converge upon zero very rapidly as p decreases in frequency. At p = 0.1 the recessive trait will express in 1% of the population (so p/p2 = 10). At p = 0.01 the recessive trait will express in 0.01% of the population (so p/p2= 100). And so forth.
It is generally understood that inbreeding has some negative biological consequences for complex animals. Recessive diseases are the most straightforward. The rarer a recessive disease is the higher and higher fraction of sufferers of that disease will be products of pairings between relatives (the reason for this is straightforward, as extremely rare alleles which express in a deleterious fashion in homozygotes will be unlikely to come together in unrelated individuals). But when it comes to traits associated with inbred individuals recessive diseases are not what comes to mind for most, the boy from the film Deliverance is usually the more gripping image (contrary to what some of the actors claimed the young boy did not have any condition).
Some are curious about the consequences of inbreeding for a trait such as intelligence. The scientific literature here is somewhat muddled. But it seems likely that all things equal if two people of average intelligence pair up and are first cousins the I.Q. of their offspring will be expected to be 0-5 points lower than would otherwise be the case. By this, I mean that the studies you can find in the literature suggest when correcting for other variables that the inbreeding depression on the phenotypic level is greater than 0 (there is an effect) but less than 5 (it is not that large, less than 1/3 of a standard deviation of the trait value). Presumably for higher levels of inbreeding the consequences are going to be more dire.
I’ve put up a bunch of posts relating to inbreeding recently (1, 2, 3, 4). But I haven’t really defined it. First, let’s stipulate what inbreeding is not: it is not the same as incest. Acts of incest can include individuals who have no blood relationship to each other (e.g., Hamlet). Additionally, there are instances of inbreeding which are not necessarily incestuous. If a population is highly inbred, then individuals who are not relations by social custom may still be so genetically similar to a point where the pairing can not credibly be stated as an outcross. But still, what do I mean? To refresh myself I re-read the section on inbreeding in Hartl & Clark. And I think that helped clarify one implicit assumption which I have which may not be clear to everyone, and I’ll get to that.
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.
The Pith: When it comes to the final outcome of a largely biologically specified trait like human height it looks as if it isn’t just the genes your parents give you that matters. Rather, the relationship of their genes also counts. The more dissimilar they are genetically, the taller you are likely to be (all things equal).
Dienekes points me to an interesting new paper in the American Journal of Physical Anthropology, Isolation by distance between spouses and its effect on children’s growth in height. The results are rather straightforward: the greater the distance between the origin of one’s parents, the taller one is likely to be, especially in the case of males. These findings were robust even after controlling for confounds such as socioeconomic status. Their explanation? Heterosis, whether through heterozygote advantage or the masking of recessive deleterious alleles.
The paper is short and sweet, but first one has to keep in mind the long history of this sort of research in the murky domain of human quantitative genetics. This is not a straight-forward molecular genetic paper where there’s a laser-like focus on one locus, and the mechanistic issues are clear and distinct. We are talking about a quantitative continuous trait, height, and how it varies within the population. We are also using geographical distance as a proxy for genetic distance. Finally, when it comes to the parameters affecting these quantitative traits there are a host of confounds, some of which are addressed in this paper. In other words, there’s no simple solution to the fact that nature can be quite the tangle, more so in some cases than others.
Because of the necessity for subtlety in this sort of statistical genetic work one must always be careful about taking results at face value. From what I can gather the history of topics such as heterosis in human genetics is always fraught with normative import. The founder of Cold Spring Harbor Laboratory, Charles Davenport, studied the outcomes of individuals who were a product of varied matings in relation to genetic distance in the early 1920s. This was summed up in his book Race Crossing in Jamaica:
A quantitative study of 3 groups of agricultural Jamaican adults: Blacks, Whites, and hybrids between them; also of several hundred children at all developmental stages. The studies are morphological, physiological, psychological, developmental and eugenical. The variability of each race and sex in respect to each bodily dimension and many basis vary just as morphological traits do. In some sensory tests the Blacks are superior to Whites; in some intellectual tests the reverse is found. A portion of the hybrids are mentally inferior to the Blacks. The negro child has, apparently, from birth on, different physical proportions than the white child.
In the wake of the post from earlier this week on the inbreeding within the House of Windsor (and current lack thereof), Luke Jostins, a subject of the British monarch, has a nice informative post up, Inbreeding, Genetic Disease and the Royal Wedding. This tidbit is of particular interest:
In fact, eleventh cousins is a pretty low degree of relatedness, by the standard of these things. A study of inbreeding in European populations found that couples from the UK are, on average, as genetically related as 6th cousins (the study looked at inbreeding in Scots, and in children of one Orkadian and one non-Orkadian. No English people, but I would be very suprised if we differed significantly). 6th cousins share about 0.006% of their DNA, and thus have about a 0.06% chance of developing a genetic disease via a common ancestor. Giving that the Royal Family are better than most at genealogy, we can probably conclude that the royal couple are less closely related than the average UK couple, and thus their children are less likely than most to suffer from a genetic disease. Good news for them, bad news for geneticists, perhaps?
On the heels of my post on cousin marriage, I thought readers might find this article on genetic screening in the United Arab Emirates of interest. One way to tackle the problem of genetic diseases which emerge out of consanguineous unions apparently isn’t to discourage the unions themselves, but dodge the outcomes. So pre-implantation screening of eggs as well as selective abortion of fetuses both seem to be options being evaluated. Aside from the costs, especially in the former case (though abortions are not without risk, and the initial stages of pregnancy are an investment of time as well), I still think there are long term problems with this. But first, Alan Bittles (who produced the map in the previous post) points to a major shortfall of a simple do-not-marry-cousins heuristic in this case:
The map above shows the distribution of consanguineous marriages. As you can see there’s a fair amount of cross-cultural variation. In the United States there’s a stereotype of cousin marriage being the practice of backward hillbillies or royalty. For typical middle class folk it’s relatively taboo, with different legal regimes by state. The history of cousin marriage in the West has been one of ups & downs. Marriage between close relatives was not unknown in antiquity. The pagan emperor Claudius married his niece Agrippina the Younger, while the Christian emperor Heraclius married his niece Martina. Marriage between cousins were presumably more common. With the rise in the West of the Roman Catholic Church marriages between cousins were officially more constrained. Adam Bellow argues in In Praise of Nepotism: A Natural History that there’s a material explanation for this: the Roman church used its power over the sacrament of marriage to control the aristocracy. Though the church required dispensations for marriages between cousins of even distant degrees of separation, they were routinely given, as was obviously the case among Roman Catholic royal families like the Hapsburgs. But once given the dispensation could be revoked, rendering the marriage null and void. A highly convenient power politically.
A few years ago you started seeing the crest of studies which basically took several hundred individuals (or thousands) from a range of locations, and then extracted out the two largest components of genetic variation from the hundreds of thousands of variants. The clusters which fell out of the genetic data, with each point being an individual’s position, were transposed onto a geographical map. The figure to the left (from this paper) has been widely circulated. You don’t have to be a deep thinker to understand why things shake out this way; people are more closely related to those near than those far because gene flow ties populations together, and its power decreases as a function of distance.
Of course the world isn’t flat, and history perturbs regularities. Jews for example often don’t shake out where they “should” geographically, because of their historical mobility contingent upon random and often capricious geopolitical or social pressures. The Hazara of Afghanistan have their ethnogenesis in the melange of peoples who were thrown together after the Mongol conquest of Central Asia and Iran in the 13th century, and the subsequent collapse of the Ilkhan dynasty. Though the Hazara have mixed with their Persian, Tajik and Pashtun neighbors, they still retain a strong stamp of Mongolian ancestry which means that they are at some remove on the “genetic map” from their geographical neighbors.