PMC:2427286 / 13238-22696 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2427286","sourcedb":"PMC","sourceid":"2427286","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2427286","text":"Results\n\nGenetic Structure within Lebanon\nThe Lebanese sample was subdivided geographically into five subpopulations: one from the capital city, Beirut, and four from other geographically distinct regions that included the Bekaa in the east, the north, the south, and the central Mount Lebanon. After excluding the Beirut individuals because of their diverse recent origins, we estimated the proportions of variation within and between the geographical subpopulations on the basis of the haplogroup frequencies (Table 3). Even within this small geographical area, a highly significant proportion of the variation (0.39%, p \u003c 0.01) was found between the regions, a conclusion reinforced by the finding that genetic distances were significantly greater than zero between several of the pairs of subpopulations when either Y-SNPs or Y-STRs were used (Table 4). The total Lebanese sample could also be subdivided according to religion (Muslim, Christian, or Druze) or religious sect (Shiite, Sunnite, Maronite, or Druze). Using these categories, we found that the proportion of variation between the subpopulations was more than three times higher (1.42%, 1.32%, both p \u003c 0.01; Table 3) than between the geographic regions. Again, many of the genetic distances between religious groups or sects were significant (Table 4). The divisions are not independent because the religious communities show geographical clustering, and when allowance was made for religious affiliation (Muslim, Christian, Druze), a Mantel test25 showed that no additional variation was explained by geographical factors (the four regions).\n\nIdentification of Potential Sources for Lebanese Genetic Structure\nBecause religious affiliation has the greatest impact on the patterns of genetic variation in Lebanese populations, and because these religions have originated within historical times, we first sought explanations for the genetic differences from the documented historical migrations: Muslim, Crusader, and Ottoman (Figure 1). Using historical evidence, we identified source regions for these migrations in the Arabian Peninsula, western Europe, and Turkey, respectively. We then collected suitable Y-chromosomal SNP datasets from these areas. For the Arabian Peninsula and Turkey this was simple, and data from France, Germany, England, and Italy15 were used to construct a suitable western European sample as described in the Material and Methods section. Because we needed to compare the Lebanese data with the same haplogroups in these additional datasets, we combined some related haplogroups to form eight haplogroups [E3b, G, I, J∗(xJ2), J2, K2, L, and R1b] that were each present in Lebanon at \u003e 4%, together accounted for 90% of the Lebanese sample, and could be compared with the categories used by other authors (Table 5).\nA standard approach to determining whether migration from these countries might have contributed to the Lebanese population would be to perform an admixture analysis with the putative source as one parental population. Taking such an approach, we could identify possible contributions from the Arabian Peninsula to Lebanese Muslims and from western Europe to Lebanese Christians, but the uncertainties in the estimates were large, and no meaningful result was obtained when Turkey was used as a potential source (Table 6). In order to investigate further, we then compared individual haplogroup frequencies in Lebanon and the putative source regions, and we identified haplogroups that differed significantly in frequency by using a Chi-square test with a Bonferroni correction for multiple testing. A number of haplogroups were found at significantly higher frequency in the potential source region than in Lebanon: J∗(xJ2) in the Arabian Peninsula, I and R1b in the western European sample, and R1b in Turkey (Table 5). Because the extent to which the western European sample used here might represent the Crusaders is uncertain, we investigated the sensitivity of our conclusion to the composition of this sample. Haplogroups I and R1b were both present at higher frequency in each of the individual populations, and the difference was significant for R1b in all four populations and for I in two of them (Germans and English). No other haplogroup was at a significantly higher frequency in any of the individual populations than in Lebanon. We therefore conclude that this is a robust finding.\nThese observations, together with the historical information, led us to formulate three specific hypotheses: that many J∗(xJ2) chromosomes were introduced into Lebanese Muslims by the Muslim expansion from the Arabian Peninsula; that some I and R1b chromosomes were introduced into Lebanese Christians by immigrating European Christians, perhaps during the time of the Crusades; and that additional R1b chromosomes were introduced into Lebanese Muslims during the Ottoman expansion. We do not, of course, imply that these migrations carried only these haplogroups; obviously, they would have involved populations containing multiple haplogroups. The signal of migration, however, should be most readily detected in the highly differentiated haplogroups. J∗(xJ2) was found to be much more frequent in Lebanese Muslims than in Lebanese non-Muslims (25% vs. 15%, p \u003c 0.0001). The combined I + R1b frequency was higher in Lebanese Christians than in Lebanese non-Christians (16% vs. 10%, p = 0.01), as were both of the individual haplogroups (I: 5.8% vs. 4.0%, p = 0.21; R1b 10% vs. 6.3%, p = 0.03), although the difference for haplogroup I alone did not reach statistical significance. The R1b frequency was, however, significantly lower in Lebanese Muslims than in Lebanese non-Muslims (4.7% vs. 11%, p = 0.0005). The hypotheses of male-mediated gene flow accompanying the earlier Muslim and Crusader migrations are therefore supported, but our data provide no evidence for a differential genetic impact of the Ottoman expansion.\n\nEvidence for Migration from Haplotype Structure\nFinally, we investigated the possible origins of the J∗(xJ2), I, and R1b chromosomes in more detail by using information from the STR haplotypes. We visualized STR haplotypes within each haplogroup by using networks28 constructed with the nine Y-STRs common to all datasets. Geographical structure was seen in the I and R1b networks (Figure 3), but not in the J∗(xJ2) network. The geographical distributions of Lebanese haplotypes were then investigated in the Y chromosome Haplotype Reference Database43 (YHRD, release 21) with seven Y-STRs so that 51,253 entries from 447 populations could be interrogated. Of the 30 Lebanese R1b haplotypes, six (representing seven individuals) were absent from the database, and 22 of the remaining 24 showed distributions that included Europe and western Asia, as would generally be expected. Most of these haplotypes thus did not provide more precise subregional information about their likely place of origin.\nOne haplotype (WES1, Western European Specific 1), however, stood out for two reasons. First, it showed a common but strictly western European distribution among the indigenous populations in the YHRD; it was present in 26/81 European populations west of Hungary and in zero populations east of this longitude (Figure 4). Second, and in contrast to its distribution in the database, it was the most common R1b haplotype in the Lebanese Christians tested (5/27, 19% of R1b, or about 2% of the total Lebanese Christian haplotypes).\nBecause this Lebanese occurrence lies far outside the normal range of this haplotype, we investigated how likely a haplotype was to rise to this frequency by chance. The first test considered the chances of observing modern levels of the WES1 haplotype among Lebanese Christians without any migration. No WES1 members were found in \u003e1,000 Middle Eastern individuals in the YHRD. Making the highly conservative assumption that its frequency p0 in the Middle East outside the Lebanese Christians was ∼0.1% (the maximum observed size consistent with zero in the sample) and a male effective population size of NL ≈1000 for the Lebanese Christians estimated from our data with BATWING, we calculated the probability of observing the modern fraction f of 2% or more as \u003c0.02 (Material and Methods). In contrast, given an input of western Europeans, selected from an evolving effective population NE ≈5000, who were carrying WES1 at 0.21% (the weighted average of the YHRD frequencies from England, France, Germany, and Italy), the probability of reaching 2% or more among Lebanese Christians exceeded 0.05 for an admixing population fraction m of ∼10.6% or greater (Table 7). It has been assumed that a total of 32 generations have passed since the start of the admixture event44, with mixing only during the first seven generations. Thus, WES1 is likely to have originated in western Europe and shows exactly the pattern expected for a European lineage introduced by the Crusaders.\nLikewise, one can test the question of whether the difference in J∗(xJ2) frequencies between Muslims (25%) and non-Muslims (15%) would have emerged by drift without enhancement during the Islamic expansion from the Arabian Peninsula by considering the probability that the 15% frequency could have drifted up to 25% or more by chance in the ∼42 generations since the Islamic expansion. For an assumed effective population size of ∼5,000, this is 0.0023, and thus, again, admixture seems likely to have contributed.","divisions":[{"label":"title","span":{"begin":0,"end":7}},{"label":"sec","span":{"begin":9,"end":1608}},{"label":"title","span":{"begin":9,"end":41}},{"label":"p","span":{"begin":42,"end":1608}},{"label":"sec","span":{"begin":1610,"end":5936}},{"label":"title","span":{"begin":1610,"end":1676}},{"label":"p","span":{"begin":1677,"end":2810}},{"label":"p","span":{"begin":2811,"end":4408}},{"label":"p","span":{"begin":4409,"end":5936}},{"label":"title","span":{"begin":5938,"end":5985}},{"label":"p","span":{"begin":5986,"end":6935}},{"label":"p","span":{"begin":6936,"end":7465}},{"label":"p","span":{"begin":7466,"end":8943}}],"tracks":[{"project":"2_test","denotations":[{"id":"18374297-6018555-2052370","span":{"begin":1512,"end":1514},"obj":"6018555"},{"id":"18374297-17275346-2052371","span":{"begin":2324,"end":2326},"obj":"17275346"},{"id":"18374297-10331250-2052372","span":{"begin":6201,"end":6203},"obj":"10331250"},{"id":"18374297-15795887-2052373","span":{"begin":8738,"end":8740},"obj":"15795887"}],"attributes":[{"subj":"18374297-6018555-2052370","pred":"source","obj":"2_test"},{"subj":"18374297-17275346-2052371","pred":"source","obj":"2_test"},{"subj":"18374297-10331250-2052372","pred":"source","obj":"2_test"},{"subj":"18374297-15795887-2052373","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93c3ec","default":true}]}]}}