Archives for posts with tag: roh

…in the united states! (just as you all suspected.) amongst white folks anyway (that’s who was included in the study below).

from a study published in 2009, Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics:

This research has definitively shown the existence of a trend for decreasing autozygosity with younger chronological age in the North American population of European ancestry. The ROHs we identified, larger than 1 Mb, are clearly representative of autozygosity due to distant consanguinity in our outbred populations, and not chromosomal abnormalities or common copy number variants. Using our predictive models of decreasing Fld, we show a quantifiable decrease in consanguinity over the twentieth century. Based on data provided in Carothers et al, this decrease in Fld found in our discovery population is on the order of individuals transitioning from a single inbreeding loop 4–5 generations prior, to no inbreeding loops within <6 generations. We postulate that the increased mobility, urbanization and outbreeding in North America in the last century has led to less consanguinity (and thus less homozygosity and homogeneity) in younger individuals.”

the researchers looked at two different sets of genomes — one from the ninds repository @the coriell institute, the other from the baltimore longitudinal study of aging (blsa). the blsa is, obviously, biased towards people on the east coast of the u.s. (in and around baltimore). glancing through the list of submitters to ninds, there’s also something of an east coast bias there, although many samples do come from other areas of the country (see the list of locations at the end of this post).

amongst the findings in this study are that 1) the number of runs of homozygosity (roh) has decreased in white americans over the last one hundred years or so, and 2) the lengths of the roh have shrunk as well. both of these are good indicators of outbreeding.

here are a couple of tables/charts from the paper (click on images for LARGER views):

measures of autozygosity in decline - table 02

measures of autozygosity in decline - percent of genome in roh

what’s interesting to contemplate, i think, is what this might mean wrt selection pressures on americans going forward? especially, what might it mean in light of european-americans encountering other, newer groups within american society that are not outbreeding so much (at least not at the moment) — newly arrived immigrants from many muslim countries, for example — or even, perhaps, latin americans (although i’m not 100% sure about how much they’ve been inbreeding over the past few hundred years or so — stay tuned!). how is that all going to play out? interesting times.

possibly related footnote — here is an abstract from the 2013 ashg conference:

“Reconstructing the Genetic Demography of the United States”

“The United States (U.S) is a complex, multiethnic society shaped by immigration and admixture, but the extent to which these forces influence the overall population genetic structure of the U.S is unknown. We utilized self-reported ancestry data collected from the decennial U.S Census 2010 and allele frequency data from over 2000 SNPs for over 40 of the most common ancestries in the U.S. that were available from the Pan Asian Single Nucleotide Polymorphism (PASNP), Population Reference Sample (POPRES), 1000 Genomes, and Human Genome Diversity Panel (HGDP) databases. We utilized the relative proportions of individuals of each ancestry within each county, state, region and nation and calculate the weighted average allele frequency in these areas. We reconstructed the genetic demography of the U.S by examining the geographic distribution of Wright’s Fst. Shannon’s diversity index, H was calculated to assess the apportionment of genetic diversity at the county, state, regional and national level. This analysis was repeated stratifying by race/ethnicity. We analyzed households with spouses, using the phi-coefficient as a measure of assortative mating for ancestry. This analysis was repeated stratifying by age of the spouses (older or younger than 50). Most of the genetic diversity is between ancestries within county, but this varies by race/ethnicity, and ranges from 95% for Whites to 43% for Hispanics illustrating that the White ancestries are relatively homogeneously scattered throughout the U.S whereas the Hispanic ancestries show significant clustering by geography. Analysis of the mating patterns show strong within ethnicity assortative mating for American Indian/Alaska Natives, Asians, Blacks, Hispanic, Native Hawaiians/Pacific Islanders, and Whites, with φ = 0.30, 0.864, 0.92, 0.863, 0.478 and 0.832 respectively (P<1×10-324 for each) and significantly less correlation in the younger cohort. These results show demographic patterns of social homogamy which are slowly decreasing over time. One major implication is that data collected from different locations around the U.S are susceptible to both within- and between-location population genetic substructure, leading to potential biases in population-based association studies.”
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origin cities of the ninds samples (from a quick-ish glance):

Burlington, VT
Lebanon, NH
Boston x 10
New York x 7
Albany
Rochester, NY x 4
New Haven x 3

Bethesda x 7
Baltimore x 5
Philadelphia
Washington, D.C.

Winston-Salem, NC
Charleston, SC

Atlanta
Birmingham x 3
Augusta

Jacksonville x 4
Tampa
Gainesville

Cincinnati x 5
Cleveland
Lexington
Louisville
Memphis
Indianapolis, IN
Ann Arbor

Chicago x 3
Springfield, IL
Rochester, MN
Minneapolis
Englewood, CO
Kansas City

Houston x 4

Phoenix
Salt Lake City

Los Angeles
Irvine, CA
Fountain Valley, CA
San Diego x 2
San Francisco x 3
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previously: runs of homozygosity and inbreeding (and outbreeding) and runs of homozygosity in the irish population and western europeans, runs of homozygosity (roh), and outbreeding and russians, eastern europeans, runs of homozygosity (roh), and inbreeding

(note: comments do not require an email. funky penguin!)

via dienekes via jayman:

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

“INTRODUCTION

“Research on consanguineous marriages, and other forms of inbreeding, has long shown a reduction in cognitive abilities in the offspring of such unions. The presumed mechanism is that detrimental recessive mutations are more likely to be identical by descent in the offspring of such unions and so have a greater chance of being expressed. To date, research on the relationship between inbreeding and cognitive ability has largely been restricted to recent inbreeding events as determined by pedigree…. It has been suggested that intellectual disability is under negative selection, and that recent deleterious mutations have an important role in the underlying aetiology. The wealth of molecular genetic data currently available allows estimates of inbreeding on a genome-wide level and to examine the effects of long-term ancestral levels of inbreeding. Such an association with inbreeding, as measured by runs of homozygous polymorphisms (ROH), has previously been identified with several behavioural traits, such as schizophreniz, Parkinson’s disease and personality measures, as well as non-behavioural traits such as height.

“The relationship between inbreeding on a population level and cognitive ability is particularly interesting due to assortative mating, non-random mating, which is greater for cognitive ability than for other behavioural traits, as well as physical traits such as height and weight. Positive assortative mating has been reported for cognitive ability, particularly for verbal traits, with spousal correlations generally around 0.5. Assortative mating should lead to greater genetic similarity between mates at causal loci for cognitive ability and to a lesser extent across the genome, which in turn reduces heterozygosity at these local. In other words, in contrast to the genome-wide reduction of heterozygosity caused by inbreeding, the reduction of heterozygosity due to assortative mating for a trait is limited to loci associated with the trait…. Another difference between inbreeding and assortative mating is that the effects of inbreeding are expected to be negative, lowering cognitive ability, whereas the effects of assortative mating affect the high, as well as the low end of the ability distribution, thus increasing genetic bariance, that is, when high-ability parents mate assortatively, their children are more likely to be homozygous for variants for high ability, just as offspring of low-ability parents are more likely to be homozygous for variants for low ability….

“MATERIALS AND METHODS

“Participants

“The Twins Early Development Study (TEDS) recruited over 11 000 families of twins born within England and Wales between 1994 and 1996…. In this analysis, individuals were excluded if they reported severe current medical problems, as well as children who had suffered severe problems at birth or whose mothers had suffered severe problems during pregnancy. Twins whose zygosity was unknown or uncertain or whose first language was not English were also excluded. Finally, analysis was restricted to twins whose parents reported their ethnicity as ‘white’….

“Cognitive measures

“Verbal and non-verbal tests were administered using web-based testing. The verbal tests consisted the Similarities subtest and the Vocabulary subtests from the Wechsler Intelligence Scale for children (WISC-III-UK). The non-verbal tests were the Picture Completion subtest from the WISC-III-UK and Conceptual Grouping from the McCarthy Scales of Children’s Abilities. A general score was derived from the test battery as the standardized sum of the standardized subtest scores, which correlates 0.99 with a score derived as the first principle component of the test battery score.

“Runs of homozygosity

“FROH was defined as the percentage of an individual’s genome consisted of runs of homozygosity (ROH)…. [O]nly ROH with a minimum of 65 consecutive SNPs covering 2.3Mb were used when calculating the total proportion of the genome covered by ROH. In addition, the required minimum density in a ROH was set at 200kb per SNP, and the maximum gap between two consecutive homozygous SNPs was set at 500kb….

“RESULTS

“Table 1 includes descriptive statistics for FROH and the three measures of cognitive ability (general, verbal, and non-verbal). FROH is slightly positively skewed, as it represents the total percentage of the genome that includes runs of homozygosity (ROH). The average percentage of genome covered by ROH was 0.7% (95% CI 0.65-0.72%). Verbal and non-verbal abilities correlate 0.49; because general cognitive ability is the sum of the standardized verbal and non-verbal subtests, they correlate much more highly with general ability (0.87 and 0.86, respectively).

inbreeding and iq - table 01

“Table 2 presents the results of the linear regression analyses. No significant regression was found between FROH and the cognitive measures after correction for multiple testing, although the association with non-verbal cognitive ability was nominally significant (P=0.03). Although this association was not statistically significant, it is noteworthy that every regression in Table 2 is *positive*, indicating that increased homozygosity tends to be associated with *higher* cognitive scores across different measures of cognitive ability (general, verbal and non-verbal).

inbreeding and iq - table 02

“Our analysis identified 87 loci where ROH overlapped in 10 or more individuals. For these overlapping regions we tested for association with each of the cognitive measures and again showed no significant associations after correction for multiple testing (P-values of less than 5.7 x 10-4). A sign test of the direction of effect across all ROH showed a disproportionately large number of *positive* associations, indicating that ROH are associated with higher cognitive ability (P=0.002). The sign test was non-significant for verbal ability but highly significant for non-verbal ability (P<10-6). The sign test for non-verbal ability alone remained significant after correcting for an individual’s genome-wide FROH score (P<10-6).

“As explained earlier, positive assortative mating can also lead to genome-wide homozygosity for trait-specific loci, and, unlike inbreeding, assortative mating can affect the high as well as the low end of the ability distribution. One possible explanation for the trend suggesting a positive correlation between homozygosity and cognitive scores in our data is that positive assortative mating on intelligence might be greater for high cognitive ability individuals….

“DISCUSSION

“Our results show that within a representative UK population sample there was a weak nominally significant association between burden of autosomal runs of homozygosity and higher non-verbal cognitive ability. This nominal association with *increased* cognitive ability is counterintuitive when compared with the results from more extreme inbreeding based on pedigree information. A potential explanation for this direction of effect is that individuals with higher cognitive ability might show greater positive assortative mating, which would lead to increased homozygosity at loci for higher cognitive ability in their offspring. However, in a separate sample we showed that greater positive assortative mating was not associated with higher cognitive ability. While these findings seem to provide clear evidence against this hypothesis, it is possible that the genome-wide genetic finding reflect historical mating habits that no longer exist today. It should also be noted that there was a reduction in the standard deviations for spousal correlations in the increased cognitive ability groups by an average of 6% compared with the decreased cognitive ability group (see Table 3), which could reflect less genetic variability in the high ability couples or a ceiling effect on the cognitive tests. This lesser phenotypic variability at the high ability end would have a small effect in reducing the spouse correlations and potentially confound our analysis….

“Overall, these results highlight the importance of understanding mating habits, such as inbreeding and assortative mating, when investigating the genetic architecture of complex traits such as cognitive ability. The results certainly suggest that there is no large effect of FROH on reduced cognitive ability, the expected direction of effect. The nominally significant associations found in this study may even suggest that in the case of non-verbal cognitive ability, beneficial associations with homozygosity at specific loci might outweigh the negative effects of genome-wide inbreeding and that the relationship between inbreeding and cognitive ability may be more complicated than previously thought.
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so, although obviously Further Research is RequiredTM, these researchers have concluded that both the absence of reduced cognitive ability and the slight increase in cognitive ability which they found in individuals who had runs of homozygosity (roh) in their genomes (evidence of matings between genetically similar individuals) were probably NOT due to assortative mating (i.e. smart people mating with smart people).

furthermore, they suggest that the inbreeding-causes-reduced-cognitive-ability meme is incorrect — or at least that the situation is more complicated than the idea that it’s the accumulation of recent deleterious mutations which haven’t been selected away that is the (whole) problem. in fact, a little inbreeding seems to have a positive effect on some cognitive abilities!

i’ve suggested a couple of times one way in which inbreeding might result in a low average iq in a population, and that is if the inbreeding leads to clannish, altruistic behaviors between extended family members which then result in the deleterious mutations NOT being weeded out.

one real world example i’ve offered is how life works in egyptian villages and how the more successful and affluent (and, presumably, more intelligent) members of a clan are obliged to help out their less successful and poorer (and, presumably, less intelligent) clan members. so, apart from mentally retarded individuals not reproducing, where is the negative selection for deleterious mutations here? there is none. or it’s a lot weaker than in more individualistic societies (like gregory clarks’ medieval england) where it’s more every man for himself — in clannish societies, deleterious mutations might be able to hang around for a long time, riding on the coattails of those with fewer deleterious mutations.

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so, after all my rambling about the historic mating patterns amongst the native irish, how inbred are the irish really?

from Population structure and genome-wide patterns of variation in Ireland and Britain:

[O]ur results suggest that the Irish population has the largest proportion of the genome in ROH (as measured by FROH1), relative to the British and HapMap CEU populations examined here (Figure 3).”

the members of the ceu population are mormons in utah. here is figure 3 — click on images for LARGER view:

ireland - roh01 - o'dushlaine et al

Figure 3 – FROH1 patterning in Irish, British and Swedish populations. Box plots represent (a) the number and (b) the summed size of segments of the autosomal genome that exists in ROH of 1 Mb or greater in length (ie, FROH1). The bars represent mean and confidence intervals, as per a standard box plot (box indicating the 25th–75th percentile of the FROH1 distribution, line within box representing the median and ends of the whiskers representing the 5th–95th percentiles). Outliers are represented by diamonds.”

so the irish: more AND longer roh or runs of homozygosity (1 Mb in length or greater) than the english, the utah mormons, scots in aberdeen, or the swedes — in that order (if i’m not mistaken). so the english here are the most outbred (what have i been saying?), while the irish are the most inbred.

more from the paper:

“Overall, the Irish and Swedish populations seem slightly different from the others in the context of ROH. Both the Irish and Swedish populations showed, on an average, a greater number of ROH, an increased maximum ROH length, as well as an increased proportion of the genome in homozygous runs, compared with that of the Scottish, southern English and Utah populations. Similarly, the mean level of individual autozygosity per population as measured by FROH22 was highest for the Irish group (Figure 4). Together, these results suggest slightly increased autozygosity in the Irish cohort compared with the British and Swedish cohorts.”

here’s figure 4:

ireland - roh02 - o'dushlaine et al

Figure 4 – Mean FROH1 and FROH5 patterning in Irish, British and Swedish populations. See Figure 1 legend for population identifiers. Y-axis indicates the average proportion of the autosomal genome covered by FROH1 or FROH5 (see Materials and Methods for definition of FROH).

“Autozygosity is generated by increased levels of kinship, which in turn reflects the population history of Ireland. Although relatively undisturbed by secondary migrations, the population of Ireland has undergone expansions and contractions at numerous points in recent history (eg, two major famines since 1600, disease epidemics, expansion in the first half of the 19th century). Aside from these features, the increased autozygosity may also reflect legacies of Gaelic family structures and comparatively low levels of migration that are in part due to a lack of industrial revolution in Ireland.

“To test a hypothesis of increased autozygosity due to features of relatively recent population history, we examined the patterning of homozygosity looking for signals of parental relatedness over the last four or five generations. Previous work has illustrated that parental relatedness arising within four to six generations predominantly affects ROH over 5 Mb in length.22 We therefore compared this statistic across populations. Results show that the Irish and Swedish populations have around 10 times as much of their genomes in ROH over 5 Mb in length than the southern English, and 1.5–3 times as much as Scotland and Utah (Figure 4)….

“Analysis of ROH is a powerful method to gauge the extent of ancient kinship and recent parental relationship within a population. This is because ROH arise from shared parental ancestry in an individual’s pedigree. The offspring of cousins have very long ROH, commonly over 10 Mb, whereas at the other end of the spectrum, almost all Europeans have ROH of ∼2 Mb in length, reflecting shared ancestry from hundreds to thousands of years ago. By focussing on ROH of different lengths, it is therefore possible to infer aspects of demographic history at different time depths in the past.22 We used FROH measures to compare and contrast patterning across populations. These measures are genomic equivalents of the pedigree inbreeding coefficient, but do not suffer from problems of pedigree reconstruction. By varying the lengths of ROH that are counted, they may be tuned to assess parental kinship at different points in the past. We used two different measures, FROH1, which includes all ROH over 1 Mb and hence includes information on recent and background parental relatedness, and FROH5, which sums ROH over 5 Mb in length, more typical of a parental relationship in the last four to six generations.22 Our FROH1 results indicate slightly elevated levels in the Irish and Swedish populations (compared with southern England, Scotland and HapMap CEU) of both the overall number of ROH and the proportion of genome in ROH (see Figure 3). This pattern was exaggerated when we restricted analysis to ROH greater than 5 Mb in length (ie, FROH5, see Figure 4), indicating increased levels of parental relatedness in the last six generations in the Irish and Swedish populations compared with other populations tested in this study. When we remove individuals with ROH over 5 Mb from the FROH1 analysis (Supplementary Figure S5), Ireland remains as the population with the most homozygous runs and the longest sum length of homozygosity. This provides further evidence that the elevated proportion of shorter ROH, and hence the number of ancient pedigree loops in Ireland, is indeed real and not driven by a limited number of offspring of cousins.

recent cousin matings, they mean.

so, if you look at figure 4, both the irish and the swedes have way more roh of over 5 Mb in lenth than the english (who have a really miniscule amount), the scots in aberdeen, or the mormons in utah (ceu) — in that order. in this instance, the swedes appear to have the most roh over 5 Mb, but as the authors say, when they removed the over 5 Mb individuals from the samples (i.e. the individuals most likely to be the offspring of recent cousin marriages), the irish wind up having the most and the longest roh over 1 Mb in length, so they win the overall inbreeding prize for these groups.

what the authors overlook, i think, is the longer term mating patterns of these populations. i think that the english in this study (and, it should be noted, that these are described as individuals from the south and southeast of england) have miniscule amounts of roh in their genomes because, out of all these groups, they have been outbreeding the longest (see “mating patterns in europe series” ↓ below in left-hand column) — since the early part of the middle ages, in fact. the irish and the swedes, on the other hand, have more roh because they started outbreeding much later (and, probably, too, because, like other northern populations, they’re somewhat remote and small in size) — the swedes sometime after they converted to christianity in — when was it? — ca. 1000 a.d.? and the irish, as i’ve shown in the last few posts on irish mating patterns, not until sometime towards the late medieval period — as late as the 1500s possibly.

the implication of all this is, because the irish and the swedes (and other groups in europe) inbred for longer than the english (and some of the french and dutch and germans), their societies would’ve remained clan- or extended-family based for longer than those of the english et al., and so would’ve been under different sorts of selection pressures from their social environment.
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update: Supplementary Figure S5 – when the researchers removed the individuals with roh over 5Mb, i.e. those individuals who were most likely to be the offspring of cousins (see comments):

ireland - roh03 - o'dushlaine et al

previously: runs of homozygosity and inbreeding (and outbreeding) and western europeans, runs of homozygosity (roh), and outbreeding and russians, eastern europeans, runs of homozygosity (roh), and inbreeding and early and late medieval irish mating practices and clannish medieval ireland and inbreeding in europe’s periphery and early modern and modern clannish ireland and meanwhile, in ireland… and drinkin’ and fightin’ songs and mating patterns, family types, and clannishness in twentieth century ireland and inbreeding in ireland in modern times

(note: comments do not require an email. clan map of ireland.)

t (thanks, t!) points me to this article (this story seems to be making the rounds this a.m.):

“All Europeans are related if you go back just 1,000 years, scientists say”

“A genetic survey concludes that all Europeans living today are related to the same set of ancestors who lived 1,000 years ago….

“The researchers were surprised to find that even individuals living as far apart as Britain and Turkey shared a chunk of genetic material 20 percent of the time. To explain that degree of genetic commonality, the researchers say those pairs of individuals would have to have a huge number of common genealogical ancestors 1,000 years ago — a number that takes in everyone who was alive in Europe back then….”

the results of the survey being discussed here have just been published on plos biology: The Geography of Recent Genetic Ancestry across Europe.

before i go on to discuss the bits i’m interested in (the identity by descent, or ibd, rates that they found), i just want to quote something from the plos article related to this business that all europeans share the same set of ancestors that lived 1,000 years ago. yes, we do, but keep in mind that:

“[S]omeone in Spain may be related to an ancestor in the Iberian peninsula through perhaps 1,000 different routes back through the pedigree, but to an ancestor in the Baltic region by only 10 different routes, so that the probability that this Spanish individual inherited genetic material from the Iberian ancestor is roughly 100 times higher. This allows the amount of genetic material shared by pairs of extant individuals to vary even if the set of ancestors is constant.”

in other words, some europeans are more related to one another than to others. but we all knew that already.

anyway…

this is the same (really awesome!) study done by ralph and coop that i posted about last year here and here. (oh, and here, too.) some of the data were available online back then after the researchers had given a presentation somewhere or other [pdf].

i’m interested in ibd data since they, like runs of homozygosity (roh), can give us some clues about how inbred or outbred populations are. it’s not a clear-cut interpretation, though, because both ibd and roh can be affected by other population genetic processes like bottlenecks and migration and simply population size (and probably other things, too, about which i am blissfully ignorant), so one has to make some educated inferences and guesses.

unfortunately, the authors don’t seem to have included in the plos publication the following illustration from their earlier presentation (unless it’s buried in the supplemental data — i didn’t see it there, but there’s a LOT of supplemental data files). that’s a shame, because it’s one of the most interesting:

coop et al - mean within-country ibd rates

the map shows the mean ibd rates for each of the european populations studied (the mean length of the blocks was >1 cM). individuals in the populations with higher mean ibd rates (bigger circles) share more identical stretches of their dna with their fellow countrymen than those in populations with low mean ibd rates. lots of outbreeding can lower the amount and lengths of ibd blocks in a population. as i posted previously, i think you can see the historic (since the early medieval period) outbreeding patterns of western europeans in the low mean ibd rates in western europe. this pattern is even clearer when you add the hajnal line to the map (the hajnal line being a good indicator of the geographical limits of the roman catholic church’s/secular authorities’ push to, amongst other things, ban cousin marriage in the medieval period).

now, here from the plos paper is a table indicating “mean number of IBD blocks shared by a pair of individuals from that population (‘self’), and mean IBD rate averaged across all other populations (‘other’)”:

ralph and coop - mean number of ibd blocks

i put the mean ibd “self” (i.e. within a population) numbers on a map and added the hajnal line. (note that the “mean length of these blocks was 2.5 cM, the median was 2.1 cM, and the 25th and 75th quantiles are 1.5 cM and 2.9 cM, respectively”.) [click on map for LARGER view.]:

europe map - ralph & coop ibd rates + hajnal line

ralph and coop suggest that the rates are so high in eastern europe, and particularly the balkans, because of the fairly recent slavic migration into the area and the fact that the slavs settled in relatively uninhabited areas. they further suggest that the germanic migrations into western europe are not so apparent in the ibd rates since these were already heavily populated areas and maybe even that the germanics were an heterogeneous group to start off with. those are really good theories (especially the one about the slavs), and i think that — yeah — we are probably seeing signals of those migrations in these data. however, once again, i think you can also see the long-term historic inbreeding/outbreeding (greater cousin marriage vs. little cousin marriage) mating patterns of european populations reflected in the ibd rates. (see “mating patterns in europe series” below ↓ in left-hand column for more details on all the mating patterns which i mention in the next few paragraphs.)

my “core europeans” — the english, the french, the belgians, the dutch, the germans, the north italians (not so much the ones in the alps, though), and to some extent the swiss and scandinavians — have the longest history of outbreeding (i.e. avoiding cousin marriage) in europe beginning in the early medieval period — and they have the lowest ibd rates. the rates are a bit higher for scandinavia since they converted to christianity later and, thus, didn’t adopt the cousin marriage bans until later. same with the irish and the scots (in fact, i think that highland scotland should be indicated as being outside the hajnal line, but that’s a discussion for another day). that the netherlands has a higher ibd rate than neighboring belgium and germany also makes sense if you know about the (probable) late adoption of the cousin marriage bans by those living in the marshes like the ditmarsians.

the ibd rates are higher east of the hajnal line and that, too, makes sense if you know that the eastern orthodox church was both later at instituting and less consistent in enforcing cousin marriage bans. the very high rates in albania and kosovo are probably related to the fact that these populations include a majority of muslims and that muslims typically have no bans on marrying cousins (while the albanians, and likely the kosovans [or whatever you want to call them!], have probably avoided paternal cousin marriage, maternal cousin marriage seems to have been an option, possibly even preferred).

the very low rate in italy is puzzling and, as i have said elsewhere, may have to do with the fact that, as the authors suggest, italy has experienced so many influxes of different populations. alternatively, it may have to do with a sampling bias (i.e. where did the italian samples come from? the more outbred north, or the more inbred south?).

the authors also broke down the ibd rates by several european regions of their own devising: “These five groupings are defined as: Europe ‘E,’ lying to the east of Germany and Austria; Europe ‘N,’ lying to the north of Germany and Poland; Europe ‘W,’ to the west of Germany and Austria (inclusive); the Iberian and Italian peninsulas ‘I'; and Turkey/Cyprus ‘TC.'” here is their table:

ralph and coop - mean number of ibd blocks by region

i made a map — and added the hajnal line (of course!):

europe map - ralph & coop regional ibd rates + hajnal line

again, there’s the east-west divide that i’ve pointed out before and which, i think, corresponds to the edge of the hajnal line. there also seems to be a north-south divide, which is apparent on both sides of the east-west (fuzzy) border, and which may have to do with long-standing lower population densities in northern europe. (that does make sense if you think about it — smaller populations inevitably experience closer matings or greater “inbreeding.”)

mating patterns matter! particularly long-term mating patterns. i think so anyway.

previously: ibd and historic mating patterns in europe and ibd rates for europe and the hajnal line and ibd rates and kindreds in germanic populations and russians, eastern europeans, runs of homozygosity (roh), and inbreeding and western europeans, runs of homozygosity (roh), and outbreeding and runs of homozygosity and inbreeding (and outbreeding) and runs of homozygosity again

(note: comments do not require an email. whatcha doin’ there?)

i thought i’d start running through pinker’s “war deaths chart” to see if i can work out any/some of these populations’ mating patterns. already posted about the semai (low violence rates, outbreeders) and the yąnomamö (greater violence rates than the semai, inbreeders).

now i’m just going to begin at the top of the list and work my way down — so today it’s the cato kato indians of california (or the cahto depending on your spelling preferences):

pinker - war deaths per 100,000 people per year - the kato

as you can see, the kato are at the top of pinker’s list. (in the 1840s, the kato were fighting the yuki, so remind me to post about them, too.)

from The North American Indian. Volume 14 [pg. 11]:

Marriage was arranged between the two persons concerned without consulting anybody else. Having secured a girl’s consent her lover went clandestinely that night to sleep with her, and at dawn he stole away. The secret was preserved as long as possible, perhaps for several days, and the news of the match transpired without formal announcement, even the girl’s parents learning of their daughter’s marriage in this indirect fashion. His marriage no longer a secret, the young man might then erect a house of his own. The bond was no more easily tied than loosed, for either could leave the other for any reason whatever, the man retaining the male children and the woman the female. Children were not regarded as belonging any more to the paternal than to the maternal side. When adultery was discovered, the only result was a little bickering and perhaps an invitation to the offender to take up permanent relations with the new love.”

sounds like cousin marriage was not insisted upon in kato society. otoh, sounds like there were no proscriptions against it, either. so matings in kato society could’ve been close — at least some of the time.

from Native Americans: An Encyclopedia of History, Culture, and Peoples [pgs. 156-57]:

Marriage was generally a matter between the couple involved, although girls were generally prepubescent when married. The Cahto practiced polygyny as well as the taboo that prevented a man from addressing his mother-in-law directly. Divorce was easily obtained for nearly any reason.”

again, no apparent insistence upon, or prohibitions against, cousin/other close marriage. however, from here [pg. 247] we learn that the pre-contact kato population was ca. 1,100 individuals. that’s not very many! with such a small population, it would be very difficult, indeed, to avoid inbreeding. (don’t forget, too, because native americans went through a bottleneck coming to the americas, they’re all relatively related to one another — genetically speaking. so any inbreeding would be even more inbred than in other populations — if that’s the right way to put it [i know it's not!].)

interestingly, from Handbook of North American Indians, Volume 8: California [pg. 244]:

“The Cahto lacked a true tribal organization. During precontact time there are estimated to have been 50 villages, with the permanent settlement situated in the three valleys where the town of Cahto once stood, and the towns of Branscomb and Laytonville now stand.”

another question is whether or not the kato married non-kato people. they were, apparently, on quite friendly terms with the pomo indians and many of them spoke pomo. did they marry out? dunno.

so, the kato? i’m gonna call it: probable inbreeding.

kato lady (she looks nice!):

Cahto_woman_curtis

previously: the semai and the fierce people

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i’ve written before (here, here and here) about the hgdp samples and the fact that there is very little to no provenance info connected to them. the problem with this, afaics, is that it’s difficult to know whether or not the hgdp samples are truly representative, in all ways, of the populations from which they came.

i was particularly concerned initially about the french (and the japanese) hgdp samples — and then i got over that — but now i’m concerned about them again. here’s why:

the hgdp samples from france are described thusly:

“France – French/various regions (relatives) – This sample from various regions of France is part of the Human Genome Diversity Cell Line Panel collected by the Human Genome Diversity Project (HGDP) and the Foundation Jean Dausset (CEPH). This sample consists of unrelated individuals and was collected with proper informed consent.”

great!

hang on — which regions?

auvergne? where, in some villages in the eighteenth century, groups of families regularly inbred with one another? lorraine? which, in some areas, had consanguinity rates of up to 50% between 1810 and 1910? burgundy or brittany, both of which had reportedly higher cousin marriage rates in the nineteenth and twentieth centuries than other regions of france? or were the hgdp samples collected in places like central france which, historically, had much lower rates (in the range of 1-3.5%) of close marriages?

the thing is: we don’t know.

what we do know is that the hgdp sampling seems kinda biased towards unique little groups like basques and orcadians, sardinians and the adygei. which is understandable ’cause these are all interesting, unusual groups and there’s legitimate concern that their unique genomes might sorta disappear in our modern, outbreeding world, and it would be a shame to miss out on the chance to at least keep a record of all that human biodiversity.

but then i have to wonder how representative of the majority of french people are the french hgdp samples? do they truly represent “the french,” or did the samples come from some of those crazy little villages way up in the mountains? i dunno. and neither does anybody else (afaik).

and the reason i wonder is: if teh scientists are gonna do really awesome genetic studies to check for the relatedness between the members of different human populations — like runs of homozygosity (roh) studies or identity by descent (ibd) studies — i think they need to know if the samples they’re looking at are representative or not. do the results for “the french” in studies like this or this or this truly represent the average french, or do they represent some special sub-groups of mountain dwelling french?

in the most recent roh study i posted about, the “french” don’t appear to be much more in- or out-bred than orcadians or the basques, something which strikes me as odd. perhaps — perhaps — that’s because the french hgdp samples are not truly representative of the broader french population. perhaps. i don’t know. nor do the researchers.

rinse and repeat above discussion for the other samples, too.

previously: hgdp samples and relatedness and more on the hgdp samples and why i care about the hgdp samples and meanwhile, in france… and runs of homozygosity and inbreeding (and outbreeding) and ibd and historic mating patterns in europe and runs of homozygosity again

(note: comments do not require an email. not out on a limb, am i?)

**update below**

here’s an exciting new paper!: Genomic Patterns of Homozygosity in Worldwide Human Populations. i don’t have access to the paper itself, but there are lots o’ neat figures and tables in the supplemental data [opens pdf] that relate to runs of homozygosity (roh). roh are identical stretches of dna within an individual’s genome (i.e. identical on each of the dna strands, paternally and maternally inherited). (roh shouldn’t be confused with blocks of identity by descent [ibd], which i did once! ibd blocks are identical stretches of dna as compared between different individuals, iiuc.)

recall that possessing lots of long roh indicates that one’s parents are/were quite similiar genetically speaking. that can be as a result of a couple of different genetic scenarios like (as greying wanderer has brought up a lot recently) simply being from a small sized population (i.e. having a small effective population size) and/or from regular inbreeding (consanguineous/endogamous mating). so, a population having a lot of long roh is either small and/or inbreeds a lot. populations having LOTS of short roh have probably been through some sort of bottleneck (see previous post).

in the paper i looked at in that previous post, the researchers had looked at the different roh lengths for large, regional populations like “europeans” or “east asians.” amongst other things, they had found that some of my regular inbreeders — the fbd marriage folks — had some of the highest numbers of medium and long roh, a state of genetic affairs which likely reflects their long-term close mating patterns. interestingly, the researchers had found that east asians had roh lengths similar to those of europeans across the board, something which surprised me since, at least according to what i’ve been reading, east asians (i.e. the chinese) have been inbreeding for a much longer time than europeans. one drawback of that previous study, though, was that, apart from the french, most of the european populations they looked at were peripheral groups who have had a tendency to inbreed more than my “core” europeans (see mating patterns in europe series below ↓ in left-hand column).

the new paper suffers from some of the same problems since the data come from the same sources (hgdp-ceph and hapmap phase 3 populations), so northern europeans — apart from the french — aren’t included in this paper either. (what can you do? it’s early days yet. i look forward to when there’s lots more genetic data available out there for teh scientists to work with! (^_^) )

what the researchers in this paper have done, though, is to look at both the different mean lengths of roh in each of the different populations sampled AND they looked at total numbers of roh within individuals for each population. this has, i think, drawn out some interesting differences between the populations.

first, here are two graphics from the supplmental data (linked to above). click on each for LARGER views (they should open in new tabs/windows — you might have to click on them again there to super-size them).

i’ve highlighted a handful of populations i want to focus on ’cause i know a little something about their historic mating patterns: the bedouin (as a proxy for the arabs — note that the bedouin have probably inbred more than more settled arabs); italians (not sure if they’re northern or southern italians or a mix of both — however, there are tuscans in the samples with which these “italians” can be compared); pathan or pastuns (more fbd marriage folks, like the bedouins/arabs); and han chinese (there are some northern han chinese with whom this groups can be compared). ok. here are the charts:

as you can see, the researchers have split up the roh into three classes (note that the short and medium classes here are a lot shorter than those in the paper looked at previously):

- A: 0.25-0.40 Mb (short)
– B: 0.6-1.2 Mb (medium)
– C: 0-35 Mb (long)

the interesting thing in the first chart above (Fig. S3 – Mean ROH Length for Each of the Three Size Classes in Each Population), is that the han chinese have lower means of roh length in all of the size classes compared to the other populations i’ve highlighted. in the previous study, the researchers found that east asians had similar means to europeans for all roh lengths. i found this surprising since, from what i’ve read, the han chinese have been inbreeding for a longer period of time than europeans. what might be confounding the results though, once again, is the fact that nw europeans (the outbreeders extraordinaire) are not really included in either of these studies apart from a handful of french samples.

in this latest study, both the bedouin and the pashtun, for instance, have higher means — and wider spreads — of long (class C) roh than the italians, which is what i would’ve expected since those two groups (the bedouins and the pashtuns) are, being fbd marriage folks, serious inbreeders. perhaps the reason the han chinese long roh mean is comparatively low is partly due to the fact that they historically practiced mother’s brother’s daughter (mbd) marriage which doesn’t push towards such close inbreeding as fbd marriage. still, i would’ve expected to see greater means of roh for the chinese than the italians — or, at least, around the same. not so much lower. (unless the italians practiced fbd marriage, too — or fzd marriage — but i don’t think so.)

if you look at the second chart (Fig. S4 – Total Number of ROH in Individual Genomes), however, you’ll see that, overall, the han chinese have more short, medium and long roh totally in individual genomes than any of the other three populations i’ve highlighted. both the bedouins and the pashtuns have greater numbers/wider total spread of long roh than the italians, but the han chinese have a much greater total number of long roh than any of the other three groups — three or four times as many.

but they’re, on average, shorter long roh don’t forget. (confusing, eh?!)

perhaps this is what you get when you have — as the chinese have had — a pretty good-sized effective population size for such a long time. there have been a LOT of han chinese for — wow — millennia.

so, it looks like this (in this order of inbrededness — i think):

- bedouins: highest mean, and very wide spread, of long roh; high total numbers, and widest spread, of long roh.
- pashtun: low mean, but widest spread, of long roh; low total number, but very wide spread, of long roh.
- han chinese: very low mean, and very narrow spread, of long roh; highest total numbers, and wide spread, of long roh.
- italians: low mean, and rather wide spread, of long roh; very low total number, and very small spread, of long roh.

other interesting points are that:

- the tuscans/tsi (toscani) appear to have lower short, medium and long mean roh than the generic “italian” category. however, the tuscans have lower total numbers of long roh than the “italians” while the toscani (tsi), on the other hand, appear to have a greater total number of long roh than the “italians.” while the tuscan samples and the toscani/tsi samples are from different studies (hgdp vs. hapmap), they are all supposed to be from tuscany, so it’s surprising that they’re so different. perhaps the individuals in the toscani/tsi sample were more closely related somehow?

- the northern han samples have lower short, medium and long mean roh than the generic “han” category. this would fit my general impression that historically inbreeding has been greater in southern china than in the north. however, the total number of long roh are greater in the northern han sample than in the “han” sample. not sure what that means.

don’t forget that there can be all sorts of reasons for differences in roh: inbreeding vs. outbreeding, yes, but also effective population size, population movement (migration in or out), bottlenecks, etc. i just happen to be interested in trying to pick out the effects of inbreeding/outbreeding — if possible.
_____

**update - here are a couple of excerpts from the article (thnx, b.b.!) [pgs. 277, 279-281]:

“Size Classification of ROH

“Separately in each population, we modeled the distribution of ROH lengths as a mixture of three Gaussian distributions that we interpreted as representing three ROH classes: (A) short ROH measuring tens of kb that probably reflect homozygosity for ancient haplotypes that contribute to local LD [linkage disequilibrium] patterns, (B) intermediate ROH measuring hundreds of kb to several Mb that probably result from background relatedness owing to limited population size, and (c) long ROH measuring multiple Mb that probably result from recent parental relatedness….

“In each population, the size distribution of ROH appears to contain multiple components (Figure 2A). Using a three-component Gaussian mixture model, we classified ROH in each population into three size classes (Figure 2B): short (class A), intermediate (class B), and long (class C). Size boundaries between different classes vary across populations (Table S1); however, considering all populations, all A-B boundaries are strictly smaller than all B-C boundaries (Figure 2C). The mean sizes of class A and B ROH are similar among populations from the same geographic region (Figure S3), with the exception that Africa and East Asia have greater variability. The class C mean is generally largest in the Middle East, Central/South Asia, and the Americas and smallest in East Asia (Figure S3), with the exception that the Tujia population has the largest values. In the admixed Mexican population (MXL), mean ROH sizes are similar to those in European populations. In the admixted African American population (ASW), however, mean ROH sizes are among the smallest in our data set, notably smaller than in most Africans and Europeans.

“Geographic Pattern of ROH

Several patterns emerge from a comparison of the per-individual total lengths of ROH across populations (Figure 3). First, the total lengths of class A (Figure 3A) and class B (Figure 3B) ROH generally increase with distance from Africa, rising in a stepwise fashion in successive continental groups. This trend is similar to the observed reduction in haplotype diversity with increasing distance from Africa. Second, total lengths of class C ROH (Figure 3C) do not show the stepwise increase. Instead, they are higher and more variable in most populations from the Middle East, Central/South Asia, Oceania, and the Americas than in most populations from Africa, Europe, and East Asia. This pattern suggests that a larger fraction of individuals from the Middle East, Central/South Asia, Oceanis, and the Americas tend to have higher levels of parental relatedness, in accordance with demographic estimates of high levels of consanguineous marriage particularly in populations from the Middle East and central/South Asia, and it is similar to that observed for inbreeding-coefficient and identity-by-descent estimates. Third, in the admixed ASW and MXL individuals, total lengths of ROH in each size class are similar to those observed in populations from Africa and Europe, respectively (Figure 3).

“The total numbers of ROH per individual (Figure S4) show similar patterns to those observed for total lengths (Figure 3). However, in East Asian populations, total numbers of class B and class C ROH per individual are notably more variable across populations than are ROH total lengths.”

previously: runs of homozygosity and inbreeding (and outbreeding) and ibd and historic mating patterns in europe

(note: comments do not require an email. ribbit!)

**update 08/03: post fixed to remove references to roh which i got wrong (roh≠blocks of ibd!) — see comments below (thanks, citrus!)**

princenuadha points me to this awesome pdf which i guess was a presentation given at a society for molecular biology and evolution (smbe) conference last weekend (thanks, prince!).

here is an interesting graphic from the presentation (pg. 21):

what this map shows are the means of runs of homozygosity (remember those?) blocks of identity by descent (ibd) that are greater than 1cM for each of these european populations. the longer the ibd blocks, the greater the identity by descent, and vice versa. small circles=fewer long blocks of ibd; large circles=more long blocks of ibd.

if a population has lots of short blocks of ibd, then its genetics are all mixed up, possibly due to outbreeding or because of a fairly recent mixing with another population. if a population has lots of long blocks of ibd, then its genetics are not so mixed up and the individuals within it share a lot of identity by descent. this can be an indicator of having been squeezed through a bottleneck or close inbreeding over time.

here are the mean numbers of long blocks of ibd for some of the countries on the map:

as you can see, my “core europeans” (english, french, germans, dutch, prolly some others) all have low means of blocks of ibd. the smallest circles are found right in the center of nw europe: england, france, belgium, germany. also italy (more about that below). in the immediate periphery around core europe, the circles are a bit larger, i.e. there are more long blocks of ibd: scotland, ireland, spain, portugal, switzerland, greece, scandinavians. eastern europeans have even larger circles/even more long blocks of ibd: poles, russians. and populations in the balkans, like the albanians, have enormous circles, i.e. LOTS of long blocks of ibd.

all of that fits the pattern i’ve been talking about here on the ol’ blog (see the mating patterns series below in the left-hand column): that the core europeans have been outbreeding the most and for the longest, with peripheral europeans lagging behind that trend, and eastern europeans really lagging behind the trend. i haven’t actually discussed the balkan populations (yet), but i do know that cousin/endogamous marriage rates are pretty high in the balkans.

i wonder if the numbers for italy may be unrepresentatively low, but it’s difficult to know. the data used are from popres and, like so much genetic data out there, have no provenance info attached to them. so, are the italian data from northern italy (which has a long history of outbreeding) or southern italy (which has a lot of inbreeding) or a combination of both? dunno.

this is a very cool study! i like it a lot. (^_^)

polish gen also has an interesting post about the presentation, btw.

(note: comments do not require an email. ruh roh!)

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