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Genetic data can provide insights into population history, but first, we must understand the patterns that complex histories leave in genomes. Here, we consider the admixed human population of Cabo Verde to understand the patterns of genetic variation left by social and demographic processes. First settled in the late 1400s, Cabo Verdeans are admixed descendants of Portuguese colonizers and enslaved West African people. We consider Cabo Verde's well-studied historical record alongside genome-wide SNP data from 563 individuals from 4 regions within the archipelago. We use genetic ancestry to test for patterns of nonrandom mating and sex-specific gene flow, and we examine the consequences of these processes for common demographic inference methods and genetic patterns. Notably, multiple population genetic tools that assume random mating underestimate the timing of admixture, but incorporating nonrandom mating produces estimates more consistent with historical records. We consider how admixture interrupts common summaries of genomic variation such as runs of homozygosity. While summaries of runs of homozygosity may be difficult to interpret in admixed populations, differentiating runs of homozygosity by length class shows that runs of homozygosity reflect historical differences between the islands in their contributions from the source populations and postadmixture population dynamics. Finally, we find higher African ancestry on the X chromosome than on the autosomes, consistent with an excess of European males and African females contributing to the gene pool. Considering these genomic insights into population history in the context of Cabo Verde's historical record, we can identify how assumptions in genetic models impact inference of population history more broadly., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Background: Association studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four Genome-Wide Association Studies (GWAS) have been carried out in these populations., Results: We present a GWAS of skin pigmentation in an admixed sample from Cuba (N = 762). Additionally, we conducted a meta-analysis including the Cuban sample, and admixed samples from Cape Verde, Puerto Rico and African-Americans from San Francisco. This meta-analysis is one of the largest efforts so far to characterize the genetic basis of skin pigmentation in admixed populations (N = 2,104). We identified five genome-wide significant regions in the meta-analysis, and explored if the markers observed in these regions are associated with the expression of relevant pigmentary genes in human melanocyte cultures. In three of the regions identified in the meta-analysis (SLC24A5, SLC45A2, and GRM5/TYR), the association seems to be driven by non-synonymous variants (rs1426654, rs16891982, and rs1042602, respectively). The rs16891982 polymorphism is strongly associated with the expression of the SLC45A2 gene. In the GRM5/TYR region, in addition to the rs1042602 non-synonymous SNP located on the TYR gene, variants located in the nearby GRM5 gene have an independent effect on pigmentation, possibly through regulation of gene expression of the TYR gene. We also replicated an association recently described near the MFSD12 gene on chromosome 19 (lead variant rs112332856). Additionally, our analyses support the presence of multiple signals in the OCA2/HERC2/APBA2 region on chromosome 15. A clear causal candidate is the HERC2 intronic variant rs12913832, which has a profound influence on OCA2 expression. This variant has pleiotropic effects on eye, hair, and skin pigmentation. However, conditional and haplotype-based analyses indicate the presence of other variants with independent effects on melanin levels in OCA2 and APBA2. Finally, a follow-up of genome-wide signals identified in a recent GWAS for tanning response indicates that there is a substantial overlap in the genetic factors influencing skin pigmentation and tanning response., Conclusions: Our meta-analysis of skin pigmentation GWAS in recently admixed populations provides new insights about the genetic architecture of this complex trait.

Genetic association studies in admixed populations are underrepresented in the genomics literature, with a key concern for researchers being the adequate control of spurious associations due to population structure. Linear mixed models (LMMs) are well suited for genome-wide association studies (GWAS) because they account for both population stratification and cryptic relatedness and achieve increased statistical power by jointly modeling all genotyped markers. Additionally, Bayesian LMMs allow for more flexible assumptions about the underlying distribution of genetic effects, and can concurrently estimate the proportion of phenotypic variance explained by genetic markers. Using three recently published Bayesian LMMs, Bayes R, BSLMM, and BOLT-LMM, we investigate an existing data set on eye ( n = 625) and skin ( n = 684) color from Cape Verde, an island nation off West Africa that is home to individuals with a broad range of phenotypic values for eye and skin color due to the mix of West African and European ancestry. We use simulations to demonstrate the utility of Bayesian LMMs for mapping loci and studying the genetic architecture of quantitative traits in admixed populations. The Bayesian LMMs provide evidence for two new pigmentation loci: one for eye color ( AHRR ) and one for skin color ( DDB1 )., (Copyright © 2017 by the Genetics Society of America.)

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

C-reactive protein (CRP) is a systemic inflammation marker that predicts future cardiovascular risk. CRP levels are higher in African Americans and Hispanic Americans than in European Americans, but the genetic determinants of CRP in these admixed United States minority populations are largely unknown. We performed genome-wide association studies (GWASs) of 8,280 African American (AA) and 3,548 Hispanic American (HA) postmenopausal women from the Women's Health Initiative SNP Health Association Resource. We discovered and validated a CRP-associated variant of triggering receptors expressed by myeloid cells 2 (TREM2) in chromosomal region 6p21 (p = 10(-10)). The TREM2 variant associated with higher CRP is common in Africa but rare in other ancestral populations. In AA women, the CRP region in 1q23 contained a strong admixture association signal (p = 10(-17)), which appears to be related to several independent CRP-associated alleles; the strongest of these is present only in African ancestral populations and is associated with higher CRP. Of the other genomic loci previously associated with CRP through GWASs of European populations, most loci (LEPR, IL1RN, IL6R, GCKR, NLRP3, HNF1A, HNF4A, and APOC1) showed consistent patterns of association with CRP in AA and HA women. In summary, we have identified a common TREM2 variant associated with CRP in United States minority populations. The genetic architecture underlying the CRP phenotype in AA women is complex and involves genetic variants shared across populations, as well as variants specific to populations of African descent., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Current information about the expansion of Bantu-speaking peoples is hampered by the scarcity of genetic data from well identified populations from southern Africa. Here, we fill an important gap in the analysis of the western edge of the Bantu migrations by studying for the first time the patterns of Y-chromosome, mtDNA and lactase persistence genetic variation in four representative groups living around the Namib Desert in southwestern Angola (Ovimbundu, Ganguela, Nyaneka-Nkumbi and Kuvale). We assessed the differentiation between these populations and their levels of admixture with Khoe-San groups, and examined their relationship with other sub-Saharan populations. We further combined our dataset with previously published data on Y-chromosome and mtDNA variation to explore a general isolation with migration model and infer the demographic parameters underlying current genetic diversity in Bantu populations., Results: Correspondence analysis, lineage sharing patterns and admixture estimates indicate that the gene pool from southwestern Angola is predominantly derived from West-Central Africa. The pastoralist Herero-speaking Kuvale people were additionally characterized by relatively high frequencies of Y-chromosome (12%) and mtDNA (22%) Khoe-San lineages, as well as by the presence of the -14010C lactase persistence mutation (6%), which likely originated in non-Bantu pastoralists from East Africa. Inferred demographic parameters show that both male and female populations underwent significant size growth after the split between the western and eastern branches of Bantu expansions occurring 4000 years ago. However, males had lower population sizes and migration rates than females throughout the Bantu dispersals., Conclusion: Genetic variation in southwestern Angola essentially results from the encounter of an offshoot of West-Central Africa with autochthonous Khoisan-speaking peoples from the south. Interactions between the Bantus and the Khoe-San likely involved cattle herders from the two groups sharing common aspects of their social organization. The presence of the -14010C mutation in southwestern Angola provides a link between the East and Southwest African pastoral scenes that might have been established indirectly, through migrations of Khoe herders across southern Africa. Differences in patterns of mtDNA and Y-chromosome intrapopulation diversity and interpopulation differentiation may be explained by contrasting demographic histories underlying the current female and male genetic variation.

There is little knowledge on the demographic impact of the western wave of the Bantu expansion. Only some predictions could be made based mainly on indirect archaeological, linguistic, and genetic evidences. Apart from the very limited available data on the mitochondrial DNA (mtDNA) side, there are not, however, Y-chromosome studies revealing-if any-the male contribution of western Bantu-farmers. To elucidate the still poorly characterized western Bantu expansion, we analyzed Y-chromosome (25 biallelic polymorphisms and 15 microsatellite markers) and mtDNA (hypervariable control regions I and II and selected coding region RFLPs) variation in a population of 110 individuals from southwest Africa, and compared it with a database of 2,708 Y-chromosome profiles and of 2,565 mtDNAs from all other regions of Africa. This study reveals (1) a dramatic displacement of male and female Khoisan-speaking groups in the southwest, since both the maternal and the paternal genetic pools were composed exclusively by types carried by Bantu-speakers; (2) a clear bias in the admixture process towards the mating of male Europeans with female Sub-Saharan Africans; (3) the assimilation of east African lineages by the southwest (mainly mtDNA-L3f and Y-chromosome-B2a lineages); and (4) signatures of recent male and female gene flow from the southeast into the southwest. The data also indicate that the western stream of the Bantu expansion was a more gradual process than the eastern counterpart, which likely involved multiple short dispersals.

Allele frequencies for seventeen STRs included in the AmpF/STR Identifiler (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPOX, and VWA) and Powerplex 16 System (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, Penta D, Penta E, TH01, TPOX, and VWA) were estimated from a sample of 110 unrelated individuals from Cabinda, Angola. Comparative analyses between our population data and other African databases, namely Promega's African-Americans, AB Applied Biosystems African-Americans and five other population samples gathered from the literature are also presented.

A collaborative exercise was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) in order to evaluate the performance of two Y-chromosome STR PCR tetraplexes, which include the loci DYS461, GATA C4, DYS437 and DYS438 (GEPY I), and DYS460, GATA A10, GATA H4 and DYS439 (GEPY II). The participating laboratories were asked to type three samples for the eight markers, using a specific amplification protocol. In addition, two control samples, with known haplotypes, were provided. The results obtained by the 13 different participating laboratories were identical, except for two laboratories that failed to type correctly the same two samples for GATA C4. By sequence analyses, two different GATA C4 allele structures were found. One control sample (allele 21) and two questioned samples (allele 22, correctly typed by all the laboratories, and allele 25) presented the following repeat structure: (TCTA)4(TGTA)2(TCTA)2(TGTA)2(TCTA)n, but different from the one found for allele 26 in one sample included in this exercise, as well as in the second control sample (allele 23), namely (TCTA)4(TGTA)2(TCTA)2(TGTA)2(TCTA)2(TGTA)2(TCTA)n. The collaborative exercise results proved that both Y-tetraplexes produce good amplification results, with the advantage of being efficiently typed using different separation and detection methodologies. However, since GATA C4 repeat presents a complex structure, with alleles differing in sequence structure, efficient denaturing conditions should be followed in order to avoid typing errors due to sizing problems.

Y-STR haplotypes are widely studied in Europe and an extensive databasing effort has been conducted (http://www.ystr.org). The distribution of these haplotypes has been considered to present no evidence for substructure at central and southern European level. This picture contrasts with the one that results from Y haplogroups defined by binary markers. This paradox has been solved by admitting that the high STR mutation rate and corresponding recurrence has erased geographic structuration. This explanation prompted us to reanalyse Y-STR haplotypes distribution bearing in mind the commonly admitted model for the generation of diversity in these markers, namely the stepwise mutation model (SMM) and, thus, taking the molecular distance between haplotypes into consideration. Accordingly, we have studied the European distribution of the two most frequent haplotypes in the Iberian Peninsula and their one step neighbours using the European samples deposited in the Y STR database (http://www.ystr.org). For the first group we found a clear-cut decreasing W-E gradient, while for the second the highest frequencies were found in the Iberian Peninsula (3.98% in Portugal and 3.85% in Spain), dropping to 2.88% in France and showing a less well defined SW-NW gradient. Furthermore, we have tested the agreement between haplotype groups and binary markers haplogroups in a random sample of 292 individuals from Northern Portugal. Our results demonstrate that (a) Y-STR haplotype data can be used for wide-scale anthropological approaches disclosing information that has been considered only available through binary markers and (b) forensic use of continental databases needs careful refinement, due to the macro-geographic pattern now evidenced.

Haplotype, allele frequencies and population data of eight Y-chromosome STR loci, DYS437, DYS438, DYS439, GATA A10, GATA A7.1, GATA A7.2, GATA C4 and GATA H4, were determined from a sample of 212 unrelated male individuals from Galicia (NW of Spain).

The Y-specific STR loci DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS434, DYS437, DYS438, DYS439 and GATA A10 were studied in a northern Portuguese population. Haplotype and allele frequencies of these 14 Y-chromosome STRs were estimated. In a sample of 212 individuals it was possible to define 196 different haplotypes of which 182 were found only once, 12 were found in 2 samples and the 2 most frequent haplotypes were shared by only 3 individuals. The observed haplotype diversity value was 0.9992. The usefulness of the inclusion of each of these new markers for forensic purposes is discussed by comparing expected and observed increases in haplotype diversity. When combining the new markers (DYS434, DYS437, DYS438, DYS439 and GATA A10) with the classical set (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393) a 0.68% increase in haplotype diversity was obtained and the number of different haplotypes rose from 157 to 196. When DYS434 was not considered the haplotype diversity was not affected.