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Polygenic scores (PGSs) summarize the combined effect of common risk variants and are associated with breast cancer risk in patients without identifiable monogenic risk factors. One of the most well-validated PGSs in breast cancer to date is PGS313, which was developed from a Northern European biobank but has shown attenuated performance in non-European ancestries. We further investigate the generalizability of the PGS313 for American women of European (EA), African (AFR), Asian (EAA), and Latinx (HL) ancestry within one institution with a singular electronic health record (EHR) system, genotyping platform, and quality control process. We found that the PGS313 achieved overlapping areas under the receiver operator characteristic (ROC) curve (AUCs) in females of HL (AUC = 0.68, 95% confidence interval [CI] = 0.65-0.71) and EA ancestry (AUC = 0.70, 95% CI = 0.69-0.71) but lower AUCs for the AFR and EAA populations (AFR: AUC = 0.61, 95% CI = 0.56-0.65; EAA: AUC = 0.64, 95% CI = 0.60-0.680). While PGS313 is associated with hormone-receptor-positive (HR+) disease in EA Americans (odds ratio [OR] = 1.42, 95% CI = 1.16-1.64), this association is lost in African, Latinx, and Asian Americans. In summary, we found that PGS313 was significantly associated with breast cancer but with attenuated accuracy in women of AFR and EAA descent within a singular health system in Los Angeles. Our work further highlights the need for additional validation in diverse cohorts prior to the clinical implementation of PGSs.

Background: High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. Objectives: This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. Results: Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f3/f4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. Conclusions: The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape. [ABSTRACT FROM AUTHOR]

It remains debatable how many genes and how various the mechanisms are behind human adaptation to extreme environments, such as high altitudes. Despite extensive studies on Tibetans, Andeans and Ethiopians, new insights are expected to be provided with careful analysis of underrepresented highlanders living in a different geographical region, such as the Tajiks, who reside on the Pamir Plateau at an average altitude exceeding 4000 meters. Moreover, genetic admixture, as we observed in the current whole-genome deep-sequencing study of Xinjiang Tajiks (XJT), offers a unique opportunity to explore how admixture may facilitate adaptation to high-altitude environments. Compared with other extensively studied highlanders, XJT showed pronounced admixture patterns: most of their ancestry are derived from West Eurasians (34.5%–48.3%) and South Asians (21.4%–40.0%), and some minor ancestry from East Asians and Siberians (3.62%–17.5%). The greater genetic diversity in XJT than in their ancestral source populations provides a genetic basis for their adaptation to high-altitude environments. The admixture gain of functional adaptive components from ancestral populations could facilitate adaptation to high-altitude environments. Specifically, admixture-facilitated adaptation was strongly associated with skin-related candidate genes that respond to UV radiation (e.g. HERC2 and BNC2) and cardiovascular-system-related genes (e.g. MPI and BEST1). Notably, no adaptive variants of genes showing outstanding natural selection signatures in the Tibetan or Andean highlanders were identified in XJT, including EPAS1 and EGLN1 , indicating that a different set of genes contributed to XJT's survival on the Pamir Plateau, although some genes underlying natural selection in XJT have been previously reported in other highlanders. Our results highlight the unique genetic adaptations in XJT and propose that admixture may play a vital role in facilitating high-altitude adaptation. By introducing and elevating diversity, admixture likely induces novel genetic factors that contribute to the survival of populations in extreme environments like the highlands. [ABSTRACT FROM AUTHOR]

Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis -expression quantitative loci (sb- cis -eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb- cis -eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes. [ABSTRACT FROM AUTHOR]

Abstract Background High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. Objectives This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. Results Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f 3 /f 4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. Conclusions The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin, genomic makeup, and genetic interaction with surrounding populations are not well understood. To decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from 4 ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from the Uyghurs in terms of their overall genomic makeup, although the 2 populations were closely related in genetics, and both showed a substantial admixture of western and eastern peoples. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5 , OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR , SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those living or along the old Silk Road. [ABSTRACT FROM AUTHOR]

Identifying hybridization between common pathogen vectors is essential due to the major public health implications through risks associated with hybrid's enhanced pathogen transmission potential. The hard‐ticks Ixodes ricinus and Ixodes persulcatus are the two most common vectors of tick‐borne pathogens that affect human and animal health in Europe. Ixodes ricinus is a known native species in Finland with a well‐known distribution, whereas I. persulcatus has expanded in range and abundance over the past 60 years, and currently it appears the most common tick species in certain areas in Finland. Here we used double‐digest restriction site‐associated DNA (ddRAD) sequencing on 186 ticks (morphologically identified as 92 I. ricinus, and 94 I. persulcatus) collected across Finland to investigate whether RAD generated single nucleotide polymorphisms (SNPs) can discriminate tick species and identify potential hybridization events. Two different clustering methods were used to assign specific species based on how they clustered and identified hybrids among them. We were able to discriminate between the two tick species and identified 11 putative hybrids with admixed genomic proportions ranging from approximately 24 to 76 percent. Four of these hybrids were morphologically identified as I. ricinus while the remaining seven were identified as I. persulcatus. Our results thus indicate that RAD SNPs are robust in identifying both species of the ticks as well as putative hybrids. These results further suggest ongoing hybridization between I. ricinus and I. persulcatus in their natural populations in Finland. The unique ability of RAD markers to discriminate between tick species and hybrids adds a useful aspect to tick evolutionary studies. Our findings align with previous studies and suggest a shared evolutionary history between the species, with instances of individuals possessing a considerable proportion of the other species' genome. This study is a significant step in understanding the formation of hybridization zones due to range expansion potentially associated with climate change. [ABSTRACT FROM AUTHOR]

Summary: Polygenic scores (PGSs) summarize the combined effect of common risk variants and are associated with breast cancer risk in patients without identifiable monogenic risk factors. One of the most well-validated PGSs in breast cancer to date is PGS313, which was developed from a Northern European biobank but has shown attenuated performance in non-European ancestries. We further investigate the generalizability of the PGS313 for American women of European (EA), African (AFR), Asian (EAA), and Latinx (HL) ancestry within one institution with a singular electronic health record (EHR) system, genotyping platform, and quality control process. We found that the PGS313 achieved overlapping areas under the receiver operator characteristic (ROC) curve (AUCs) in females of HL (AUC = 0.68, 95% confidence interval [CI] = 0.65–0.71) and EA ancestry (AUC = 0.70, 95% CI = 0.69–0.71) but lower AUCs for the AFR and EAA populations (AFR: AUC = 0.61, 95% CI = 0.56–0.65; EAA: AUC = 0.64, 95% CI = 0.60–0.680). While PGS313 is associated with hormone-receptor-positive (HR+) disease in EA Americans (odds ratio [OR] = 1.42, 95% CI = 1.16–1.64), this association is lost in African, Latinx, and Asian Americans. In summary, we found that PGS313 was significantly associated with breast cancer but with attenuated accuracy in women of AFR and EAA descent within a singular health system in Los Angeles. Our work further highlights the need for additional validation in diverse cohorts prior to the clinical implementation of PGSs.

This research explores how biracial facial cues affect racial perception and social judgment. We tested a coalition-signaling hypothesis of biracial cues in two studies conducted in the United States (n=227) and China (n=116). From the perspective of intergroup and interpersonal relations theories in social psychology, biracial features would likely be perceived as cues of threat or resource competition. In contrast, we propose an evolutionary hypothesis that biracial facial cues reveal the ancestral history of intergroup alliances between members of two races or ethnic groups. When racial cues are mixed, we predict that biracial individuals may be viewed more positively than other-race or even own-race members who often compete for limited ingroup resources. The participants observed facial images that ranged from 100% Asian to 100% Caucasian, including morphed biracial composites of 30%, 40%, 50%, 60%, and 70% Caucasian or Asian. The participants evaluated each image regarding perceived Caucasianness (Asianness), attractiveness, trustworthiness, health, intelligence, and career prospects. The US and Chinese samples yielded a similar pattern of own-race bias in racial perception and biracial favoritism in social judgment. The social judgment ratings were not correlated with the racial perception scores and were independent of the sex of the participants or biracial images, indicating a coalitional motive, instead of a mating motive, underlying social perception of biracial individuals. Overall, the results suggest that biracial facial features signal a successful genetic admixture and coalition in parental generations and thus increase the trustworthiness and cooperative potential of a biracial person. [ABSTRACT FROM AUTHOR]

Mandarins are one of the members of the genus Citrus L. which contain very important plant species that extensively contribute to humans. The classification of commercial mandarins is very complicated, which largely includes tangerine, satsuma, and clementine. Citrus hybrids are more diversified, and their taxonomy is somewhat inconsistent. A proper breeding and conservation plan for important plant species requires accurate genetic analysis and an evaluation of the available germplasm. The present study was conducted to produce data on genetic structure, gene flow, and admixture of the mandarin populations in Iran and also to identify the genetic regions associated with geographical and climatic variables. The start codon targeted molecular markers were used for this study. The results revealed some extent of gene flow and genetic admixture among mandarin populations and that some locally named cultivars are genetically alike and probably are homonyms. Mandarins comprise a complex genetic group of closely related individuals, but yet somewhat genetically differentiated probably due to local propagation practice and artificial selection by orchard management, as revealed by significant analysis of molecular variance. The accessions studied were grouped into three broad genetic groups which differ in their genetic content and may be used for the breeding program of mandarins. We also identified some genetic regions which are significantly associated with an environmental and climatic variable which can be used in the conservation program of mandarins in the country. Landscape genetic analyses revealed that both global and local spatial variables affect the genetic structuring of mandarins. [ABSTRACT FROM AUTHOR]

Abstract Identifying hybridization between common pathogen vectors is essential due to the major public health implications through risks associated with hybrid's enhanced pathogen transmission potential. The hard‐ticks Ixodes ricinus and Ixodes persulcatus are the two most common vectors of tick‐borne pathogens that affect human and animal health in Europe. Ixodes ricinus is a known native species in Finland with a well‐known distribution, whereas I. persulcatus has expanded in range and abundance over the past 60 years, and currently it appears the most common tick species in certain areas in Finland. Here we used double‐digest restriction site‐associated DNA (ddRAD) sequencing on 186 ticks (morphologically identified as 92 I. ricinus, and 94 I. persulcatus) collected across Finland to investigate whether RAD generated single nucleotide polymorphisms (SNPs) can discriminate tick species and identify potential hybridization events. Two different clustering methods were used to assign specific species based on how they clustered and identified hybrids among them. We were able to discriminate between the two tick species and identified 11 putative hybrids with admixed genomic proportions ranging from approximately 24 to 76 percent. Four of these hybrids were morphologically identified as I. ricinus while the remaining seven were identified as I. persulcatus. Our results thus indicate that RAD SNPs are robust in identifying both species of the ticks as well as putative hybrids. These results further suggest ongoing hybridization between I. ricinus and I. persulcatus in their natural populations in Finland. The unique ability of RAD markers to discriminate between tick species and hybrids adds a useful aspect to tick evolutionary studies. Our findings align with previous studies and suggest a shared evolutionary history between the species, with instances of individuals possessing a considerable proportion of the other species' genome. This study is a significant step in understanding the formation of hybridization zones due to range expansion potentially associated with climate change.

Pathogen‒host adaptative interactions and complex population demographical processes, including admixture, drift, and Darwen selection, have considerably shaped the Neolithic-to-Modern Western Eurasian population structure and genetic susceptibility to modern human diseases. However, the genetic footprints of evolutionary events in East Asia remain unknown due to the underrepresentation of genomic diversity and the design of large-scale population studies. We reported one aggregated database of genome-wide SNP variations from 796 Tai-Kadai (TK) genomes, including that of Bouyei first reported here, to explore the genetic history, population structure, and biological adaptative features of TK people from southern China and Southeast Asia. We found geography-related population substructure among TK people using the state-of-the-art population genetic structure reconstruction techniques based on the allele frequency spectrum and haplotype-resolved phased fragments. We found that the northern TK people from Guizhou harbored one TK-dominant ancestry maximized in the Bouyei people, and the southern TK people from Thailand were more influenced by Southeast Asians and indigenous people. We reconstructed fitted admixture models and demographic graphs, which showed that TK people received gene flow from ancient southern rice farmer-related lineages related to the Hmong-Mien and Austroasiatic people and from northern millet farmers associated with the Sino-Tibetan people. Biological adaptation focused on our identified unique TK lineages related to Bouyei, which showed many adaptive signatures conferring Malaria resistance and low-rate lipid metabolism. Further gene enrichment, the allele frequency distribution of derived alleles, and their correlation with the incidence of Malaria further confirmed that CR1 played an essential role in the resistance of Malaria in the ancient ''Baiyue'' tribes.

Abstract Background Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. Methods and study population We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. Results The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970–0.978, p = 3.1 × 10–40). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987–0.990, p = 1.4 × 10–44). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952–0.964; Mexican women: OR = 0.973, 95% CI 0.969–0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. Conclusions The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies.

The heritability explained by local ancestry markers in an admixed population (h γ 2) provides crucial insight into the genetic architecture of a complex disease or trait. Estimation of h γ 2 can be susceptible to biases due to population structure in ancestral populations. Here, we present heritability estimation from admixture mapping summary statistics (HAMSTA), an approach that uses summary statistics from admixture mapping to infer heritability explained by local ancestry while adjusting for biases due to ancestral stratification. Through extensive simulations, we demonstrate that HAMSTA h γ 2 estimates are approximately unbiased and are robust to ancestral stratification compared to existing approaches. In the presence of ancestral stratification, we show a HAMSTA-derived sampling scheme provides a calibrated family-wise error rate (FWER) of ∼5% for admixture mapping, unlike existing FWER estimation approaches. We apply HAMSTA to 20 quantitative phenotypes of up to 15,988 self-reported African American individuals in the Population Architecture using Genomics and Epidemiology (PAGE) study. We observe h ˆ γ 2 in the 20 phenotypes range from 0.0025 to 0.033 (mean h ˆ γ 2 = 0.012 ± 9.2 × 10−4), which translates to h ˆ 2 ranging from 0.062 to 0.85 (mean h ˆ 2 = 0.30 ± 0.023). Across these phenotypes we find little evidence of inflation due to ancestral population stratification in current admixture mapping studies (mean inflation factor of 0.99 ± 0.001). Overall, HAMSTA provides a fast and powerful approach to estimate genome-wide heritability and evaluate biases in test statistics of admixture mapping studies. This study reports a method to estimate heritability explained by local ancestry using admixture mapping summary statistics and evaluates potential biases in admixture mapping. The method provides a strategy for summary statistic-based heritability estimation in admixed populations and controlling false positives due to ancestral population stratification in admixture mapping studies. [ABSTRACT FROM AUTHOR]

Background: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. Methods and study population: We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. Results: The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970–0.978, p = 3.1 × 10–40). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987–0.990, p = 1.4 × 10–44). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952–0.964; Mexican women: OR = 0.973, 95% CI 0.969–0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. Conclusions: The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies. [ABSTRACT FROM AUTHOR]

Simple Summary: An association between individual levels of indigenous Chilean Mapuche ancestry and the risk of gallbladder cancer has been reported in observational studies, and the current program for gallbladder prevention in Chile takes the number of Mapuche surnames into account for prophylactic cholecystectomy. However, the association between Mapuche ancestry and gallbladder cancer could be due to known and unknown confounders (e.g., overweight and obesity) and non-random measurement errors (e.g., socio-economic level and access to health care). To investigate whether Mapuche ancestry and gallbladder cancer risk are statistically correlated or causally related, we used ancestry-informative markers for instrumental variable analysis. We aim to provide robust evidence on the potential of accounting for ethnic differences (in this study, Mapuche ancestry) for disease interception (in this study, gallbladder cancer prevention through prophylactic cholecystectomy). The methodology used and the results obtained may also guide future admixture mapping studies. A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10−5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate −0.006 kg/m2, 95% CI −0.009 to −0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient. [ABSTRACT FROM AUTHOR]

Allopolyploidy is considered as a principal driver that shaped angiosperms' evolution in terms of diversification and speciation. Despite the unexpected high frequency of polyploidy that was recently discovered in the coniferous genus Juniperus, little is known about the origin of these polyploid taxa. Here, we conducted the first study devoted to deciphering the origin of the only hexaploid taxon in Juniperus along with four of its closely related tetraploid taxa using AFLP markers with four primers combinations. Phylogenetic analysis revealed that the 10 studied species belong to 2 major clusters. J. foetidissima appeared to be more related to J. thurifera, J. sabina, and J. chinensis. The Bayesian clustering analysis showing a slight variation in genetic admixture between the studied populations of J. foetidissima, suggesting an allopolyploid origin of this species involving J. thurifera and J. sabina lineages, although a purely autopolyploidy origin of both J. thurifera and J. foetidissima cannot be ruled out. The admixed genetic pattern revealed for J. seravschanica showed that the tetraploid cytotypes of this species originated from allopolyploidy, whereas no clear evidence of hybridization in the origin of the tetraploid J. thurifera and J. chinensis was detected. This study provides first insights into the polyploidy origin of the Sabina section and highlights the potential implication of allopolyploidy in the evolution of the genus Juniperus. Further analyses are needed for a more in-depth understanding of the evolutionary scenarios that produced the observed genetic patterns. [ABSTRACT FROM AUTHOR]

ABSTRACT: Genomic admixture is a widespread phenomenon among domestic animal breeds, including chickens. However, reports on admixture within Chinese gamecocks or other indigenous chickens are limited. This study focuses on the population genetic structure and admixture of 5 Chinese gamecock breeds and the admixture with 9 other indigenous Chinese chicken breeds. Our results showed that Turpan and Henan gamecocks were grouped into one cluster, whereas Luxi, Zhangzhou, and Xishuangbanna gamecocks were grouped into the other cluster. Gene flow occurred between Xishuangbanna and Turpan and Turpan and Luxi gamecocks. Simultaneously, gene flow was observed between gamecocks and indigenous chickens, such as Xishuangbanna and Wenchang. Ancestral component analysis indicated that modern domestic chickens in southern China played an important role in the history of the domestication of modern Chinese gamecock. Our study will be helpful in better understanding the domestication and evolution of Chinese gamecock.

Deleterious mutation loads are known to correlate negatively with effective population size (Ne). Due to this reason, previous studies observed a higher proportion of harmful mutations in small populations than that in large populations. However, the mutational load in an admixed population that derived from introgression between individuals from two populations with vastly different Ne is not known. We investigated this using the whole genome data from two subspecies of the mouse (Mus musculus castaneus and Mus musculus musculus) with significantly different Ne. We used the ratio of diversities at nonsynonymous and synonymous sites (dN/dS) to measure the harmful mutation load. Our results showed that this ratio observed for the admixed population was intermediate between those of the parental populations. The dN/dS ratio of the hybrid population was significantly higher than that of M. m. castaneus but lower than that of M. m. musculus. Our analysis revealed a significant positive correlation between the proportion of M. m. musculus ancestry in admixed individuals and their dN/dS ratio. This suggests that the admixed individuals with high proportions of M. m. musculus ancestry have large dN/dS ratios. We also used the proportion of deleterious nonsynonymous SNVs as a proxy for deleterious mutation load, which also produced similar results. The observed results were in concordance with those expected by theory. We also show a shift in the distribution of fitness effects of nonsynonymous SNVs in the admixed genomes compared to the parental populations. These findings suggest that the deleterious mutation load of the admixed population is determined by the proportion of the ancestries of the subspecies. Therefore, it is important to consider the status and the level of genetic admixture of the populations whilst estimating the mutation loads.

Even though Guatemala is considered one of the three domestication centres of the avocado (Persea americana Mill), little is known about the genetic diversity of its native populations. This is the first study to explore avocado genetic diversity and population structure in native dispersal areas using microsatellite markers. We sampled 189 avocado trees grown from seeds in eight geographical populations, and 12 microsatellite loci were tested for diversity. There were a total of 289 alleles found throughout the 12 loci, with an average of 23.83 alleles per locus. The average observed and expected heterozygosity were 0.53 and 0.83, respectively. The analysis of molecular variance revealed that the eight populations comprised around 2% of the variation. Five of the 28 G'ST(Nei) pairwise comparisons indicated no genetic difference. We discovered a mixture of avocado trees from various populations using unweighted pair group method with arithmetic mean (UPGMA) hierarchical cluster analysis. The sampled individuals were classified into three main genetic clusters by the model-based STRUCTURE and discriminant analysis of principal components (DAPC). The weak genetic structure exhibited by mixing avocado trees from different populations could be mainly attributed to high human-mediated gene flow (Nm = 12.25) due to avocado's importance in food, culture, and Guatemala's religion. The high genetic diversity found in the avocado germplasm suggests that it might be a valuable source of variable alleles that could be used in breeding programs for this crop in Guatemala. [ABSTRACT FROM AUTHOR]

As the most prevalent aboriginal group on Hainan Island located between South China and the mainland of Southeast Asia, the Li people are believed to preserve some unique genetic information due to their isolated circumstances, although this has been largely uninvestigated. We performed the first whole-genome sequencing of 55 Hainan Li (HNL) individuals with high coverage (∼30–50×) to gain insight into their genetic history and potential adaptations. We identified the ancestry enriched in HNL (∼85%) is well preserved in present-day Tai-Kadai speakers residing in South China and North Vietnam, that is, Bai-Yue populations. A lack of admixture signature due to the geographical restriction exacerbated the bottleneck in the present-day HNL. The genetic divergence among Bai-Yue populations began ∼4,000–3,000 years ago when the proto-HNL underwent migration and the settling of Hainan Island. Finally, we identified signatures of positive selection in the HNL, some outstanding examples included FADS1 and FADS2 related to a diet rich in polyunsaturated fatty acids. In addition, we observed that malaria-driven selection had occurred in the HNL, with population-specific variants of malaria-related genes (e.g. CR1) present. Interestingly, HNL harbors a high prevalence of malaria leveraged gene variants related to hematopoietic function (e.g. CD3G) that may explain the high incidence of blood disorders such as B-cell lymphomas in the present-day HNL. The results have advanced our understanding of the genetic history of the Bai-Yue populations and have provided new insights into the adaptive scenarios of the Li people. [ABSTRACT FROM AUTHOR]

Sex-biased gene flow has been common in the demographic history of modern humans. However, the lack of sophisticated methods for delineating the detailed sex-biased admixture process prevents insights into complex admixture history and thus our understanding of the evolutionary mechanisms of genetic diversity. Here, we present a novel algorithm, MultiWaverX , for modeling complex admixture history with sex-biased gene flow. Systematic simulations showed that MultiWaverX is a powerful tool for modeling complex admixture history and inferring sex-biased gene flow. Application of MultiWaverX to empirical data of 17 typical admixed populations in America, Central Asia, and the Middle East revealed sex-biased admixture histories that were largely consistent with the historical records. Notably, fine-scale admixture process reconstruction enabled us to recognize latent sex-biased gene flow in certain populations that would likely be overlooked by much of the routine analysis with commonly used methods. An outstanding example in the real world is the Kazakh population that experienced complex admixture with sex-biased gene flow but in which the overall signature has been canceled due to biased gene flow from an opposite direction. [ABSTRACT FROM AUTHOR]

To identify key traits brought about by citrus domestication, we have analyzed the transcriptomes of the pulp of developing fruitlets of inedible wild Ichang papeda (Citrus ichangensis), acidic Sun Chu Sha Kat mandarin (C. reticulata) and three palatable segregants of a cross between commercial Clementine (C. x clementina) and W. Murcott (C. x reticulata) mandarins, two pummelo/mandarin admixtures of worldwide distribution. RNA-seq comparison between the wild citrus and the ancestral sour mandarin identified 7267 differentially expressed genes, out of which 2342 were mapped to 117 KEGG pathways. From the remaining genes, a set of 2832 genes was functionally annotated and grouped into 45 user-defined categories. The data suggest that domestication promoted fundamental growth processes to the detriment of the production of chemical defenses, namely, alkaloids, terpenoids, phenylpropanoids, flavonoids, glucosinolates and cyanogenic glucosides. In the papeda, the generation of energy to support a more active secondary metabolism appears to be dependent upon upregulation of glycolysis, fatty acid degradation, Calvin cycle, oxidative phosphorylation, and ATP-citrate lyase and GABA pathways. In the acidic mandarin, downregulation of cytosolic citrate degradation was concomitant with vacuolar citrate accumulation. These changes affected nitrogen and carbon allocation in both species leading to major differences in organoleptic properties since the reduction of unpleasant secondary metabolites increases palatability while acidity reduces acceptability. The comparison between the segregants and the acidic mandarin identified 357 transcripts characterized by the occurrence in the three segregants of additional downregulation of secondary metabolites and basic structural cell wall components. The segregants also showed upregulation of genes involved in the synthesis of methyl anthranilate and furaneol, key substances of pleasant fruity aroma and flavor, and of sugar transporters relevant for sugar accumulation. Transcriptome and qPCR analysis in developing and ripe fruit of a set of genes previously associated with citric acid accumulation, demonstrated that lower acidity is linked to downregulation of these regulatory genes in the segregants. The results suggest that the transition of inedible papeda to sour mandarin implicated drastic gene expression reprograming of pivotal pathways of the primary and secondary metabolism, while palatable mandarins evolved through progressive refining of palatability properties, especially acidity. [ABSTRACT FROM AUTHOR]

While whole-genome sequencing has been applied extensively to investigate the genetic diversity of global populations, ethnic minority groups in Pakistan are generally underrepresented. In particular, little is known about the genetic origin and highland adaptation of the Pamirian Wakhi people. According to Chinese historical records, the geographical location and language usage of Wakhi may be closely related to Xinjiang Tajiks (XJT). In this study, based on high-coverage (∼30×) whole-genome sequencing of eight Wakhi and 25 XJT individuals, we performed data analyses together with worldwide populations to gain insights into their genetic composition, demography, and adaptive evolution to the highland environment. The Wakhi derived more than 85% of their ancestry from West Eurasian populations (European ∼44.5%, South Asian ∼42.2%) and 10% from East Eurasian populations (Siberian ∼6.0%, East Asian ∼4.3%). Modeling the admixture history of the Wakhi indicated that the early West-East admixture occurred approximately 3,875-2,250 years ago and that the recent admixture occurred 750-375 years ago. We identified selection signatures across EGLN3, in particular, a distinctive evolutionary signature was observed, and a certain underlying selected haplotype showed higher frequency (87.5%) in the Wakhi than in nearby XJT and other highlanders. Interestingly, we found high-frequency archaic sequences in the Wakhi genome, which overlapped with several genes related to cellular signaling transduction, including MAGI2, previously associated with high-altitude adaptation. Our analysis indicates that the Wakhi are distinct from the XJTs and Tajikistan Tajiks, and shed light on the Wakhi's ancestral origin and genetic basis of high-altitude adaptation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Human admixture history is rarely a simple process in which distinct populations, previously isolated for a long time, come into contact once to form an admixed population. In this study, we aim to reconstruct the complex admixture histories of the population of São Tomé, an island in the Gulf of Guinea that was the site of the first slave-based plantation economy, and experienced successive waves of forced and deliberate migration from Africa. We examined 2.5 million SNPs newly genotyped in 96 São Toméans and found that geography alone cannot explain the observed patterns of genetic differentiation within the island. We defined five genetic groups in São Tomé based on the hypothesis that individuals sharing the most haplotypes are more likely to share similar genetic histories. Using Identical-by-Descent and different local ancestry inference methods, we inferred shared ancestries between 70 African and European populations and each São Toméan genetic group. We identified admixture events between admixed groups that were previously isolated on the island, showing how recently admixed populations can be themselves the sources of other admixture events. This study demonstrates how complex admixture and isolation histories during and after the Transatlantic Slave-Trade shaped extant individual genetic patterns at a local scale in Africa., Competing Interests: The authors declare no competing interests.

To identify key traits brought about by citrus domestication, we have analyzed the transcriptomes of the pulp of developing fruitlets of inedible wild Ichang papeda (Citrus ichangensis), acidic Sun Chu Sha Kat mandarin (C. reticulata) and three palatable segregants of a cross between commercial Clementine (C. x clementina) and W. Murcott (C. x reticulata) mandarins, two pummelo/mandarin admixtures of worldwide distribution. RNA-seq comparison between the wild citrus and the ancestral sour mandarin identified 7267 differentially expressed genes, out of which 2342 were mapped to 117 KEGG pathways. From the remaining genes, a set of 2832 genes was functionally annotated and grouped into 45 user-defined categories. The data suggest that domestication promoted fundamental growth processes to the detriment of the production of chemical defenses, namely, alkaloids, terpenoids, phenylpropanoids, flavonoids, glucosinolates and cyanogenic glucosides. In the papeda, the generation of energy to support a more active secondary metabolism appears to be dependent upon upregulation of glycolysis, fatty acid degradation, Calvin cycle, oxidative phosphorylation, and ATP-citrate lyase and GABA pathways. In the acidic mandarin, downregulation of cytosolic citrate degradation was concomitant with vacuolar citrate accumulation. These changes affected nitrogen and carbon allocation in both species leading to major differences in organoleptic properties since the reduction of unpleasant secondary metabolites increases palatability while acidity reduces acceptability. The comparison between the segregants and the acidic mandarin identified 357 transcripts characterized by the occurrence in the three segregants of additional downregulation of secondary metabolites and basic structural cell wall components. The segregants also showed upregulation of genes involved in the synthesis of methyl anthranilate and furaneol, key substances of pleasant fruity aroma and flavor, and of sugar transporters relevant for sugar accumulation. Transcriptome and qPCR analysis in developing and ripe fruit of a set of genes previously associated with citric acid accumulation, demonstrated that lower acidity is linked to downregulation of these regulatory genes in the segregants. The results suggest that the transition of inedible papeda to sour mandarin implicated drastic gene expression reprograming of pivotal pathways of the primary and secondary metabolism, while palatable mandarins evolved through progressive refining of palatability properties, especially acidity.

Allopolyploidy is considered as a principal driver that shaped angiosperms’ evolution in terms of diversification and speciation. Despite the unexpected high frequency of polyploidy that was recently discovered in the coniferous genus Juniperus, little is known about the origin of these polyploid taxa. Here, we conducted the first study devoted to deciphering the origin of the only hexaploid taxon in Juniperus along with four of its closely related tetraploid taxa using AFLP markers with four primers combinations. Phylogenetic analysis revealed that the 10 studied species belong to 2 major clusters. J. foetidissima appeared to be more related to J. thurifera, J. sabina, and J. chinensis. The Bayesian clustering analysis showing a slight variation in genetic admixture between the studied populations of J. foetidissima, suggesting an allopolyploid origin of this species involving J. thurifera and J. sabina lineages, although a purely autopolyploidy origin of both J. thurifera and J. foetidissima cannot be ruled out. The admixed genetic pattern revealed for J. seravschanica showed that the tetraploid cytotypes of this species originated from allopolyploidy, whereas no clear evidence of hybridization in the origin of the tetraploid J. thurifera and J. chinensis was detected. This study provides first insights into the polyploidy origin of the Sabina section and highlights the potential implication of allopolyploidy in the evolution of the genus Juniperus. Further analyses are needed for a more in-depth understanding of the evolutionary scenarios that produced the observed genetic patterns.

Background Hmong-Mien speaking Miao, also called Hmong, is the sixth largest ethnic group in mainland China. However, the fine-scale genetic profiles and population history of Miao populations in southwest China, especially in Guizhou province, remain uncharacterised due to a scarcity of samples of genome-wide data from different tribes. Aim To further investigate the population substructure and admixture history of the Guizhou Miao minority. Subjects and methods We collected 29 samples from three Miao tribes of Guizhou province in southwest China and genotyped about 700,000 genome-wide SNPs of each sample. We analysed newly generated data in together with published modern/ancient East Asian populations datasets via a series of population genetic methods, including principal component analysis (PCA), ADMIXTURE, Fst, TreeMix, f-statistics, qpWave, and qpAdm. Results PCA and ADMIXTURE results showed that the three studied Guizhou Miao groups consistently fell on the Hmong-Mien-related genetic cline and were relatively genetically homogeneous, displaying a genetic affinity with neighbouring Tai-Kadai speaking populations such as Dong. These results were further confirmed by the observed genetic clade in Fst, TreeMix, outgroup-f3-statistics, and f4-statistics. Furthermore, f4-based allele sharing patterns illustrated that compared with Hunan Miao in central China, Guizhou Miao shared more alleles with Hmong-Mien-speaking Vietnam Hmong and Tai-Kadai-speaking CoLao, Dong, while exhibiting less northeast Asian-related ancestry. Admixture-f3 and f4-statistics revealed the North-South admixture pattern for the studied Guizhou Miao. A qpAdm-based two-way admixture model further revealed that the studied Guizhou Miao harboured 44%–55.4% indigenous Austronesian-speaking Atayal-related ancestry and 44.6%–56% Late Neolithic Yellow River farmer-related ancestry. Conclusions The population structure within Hmong-Mien-related populations showed a geographic correlation. Hmong-Mien speaking Hunan Miao, Guizhou Miao, and Vietnam Hmong presented close genetic relationships although they dwelt in different regions, suggesting the preservation of the original Hmong-related genetic diversity. The results based on genome-wide SNPs data generally matched the migration history for the Miao population. Our study contributes to a better knowledge of Miao populations and the population structure in southwest China.

• Using MEGA-ex array genotype data, we characterized the genetic ancestral admixture of two South African Cape Coloured (SACC) longitudinal birth cohorts (N=308 mothers, 280 children) designed to examine effects of prenatal alcohol exposure on development. The cohorts showed global African (51 %; Bantu and San); European (26 %; Northern/Western); South Asian (18 %); and East Asian (5 %; largely Southern regions) ancestries. • Rare variants were overrepresented in our SACC cohorts, with numerous polymorphisms being monomorphic in other reference populations. • The cohorts exhibited high rates of homozygosity (6%), with regions of homozygosity harboring more deleterious variants when lying within African local-ancestry genomic segments. • Both maternal and child ancestry profiles were associated with risk of full or partial fetal alcohol syndrome in the child, as well as altered severity of prenatal alcohol exposure-related cognitive deficits. Ancestrally admixed populations are underrepresented in genetic studies of complex diseases, which are still dominated by European-descent populations. This is relevant not only from a representation standpoint but also because of admixed populations' unique features, including being enriched for rare variants, for which effect sizes are disproportionately larger than common polymorphisms. Furthermore, results from these populations may be generalizable to other populations. The South African Cape Coloured (SACC) population is genetically admixed and has one of the highest prevalences of fetal alcohol spectrum disorders (FASD) worldwide. We profiled its admixture and examined associations between ancestry profiles and FASD outcomes using two longitudinal birth cohorts (N =308 mothers, 280 children) designed to examine effects of prenatal alcohol exposure on development. Participants were genotyped via MEGAex array to capture common and rare variants. Rare variants were overrepresented in our SACC cohorts, with numerous polymorphisms being monomorphic in other reference populations (e.g., ∼30,000 and ∼ 221,000 variants in gnomAD European and Asian populations, respectively). The cohorts showed global African (51 %; Bantu and San); European (26 %; Northern/Western); South Asian (18 %); and East Asian (5 %; largely Southern regions) ancestries. The cohorts exhibited high rates of homozygosity (6 %), with regions of homozygosity harboring more deleterious variants when lying within African local-ancestry genomic segments. Both maternal and child ancestry profiles were associated with higher FASD risk, and maternal and child ancestry-by-prenatal alcohol exposure interaction effects were seen on child cognition. Our findings indicate that the SACC population may be a valuable asset to identify novel disease-associated genetic loci for FASD and other diseases. [ABSTRACT FROM AUTHOR]

ObjectiveIn the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1 second (FEV1) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma.MethodsAs part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8-21 years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629). We investigated the association between any breastfeeding in infancy and FEV1% predicted using multivariable linear regression; Poisson regression was used to determine the association between breastfeeding and asthma exacerbations.ResultsPrevalence of breastfeeding was lower in African Americans (59.4%) and Puerto Ricans (54.9%) compared to Mexican Americans (76.2%) and mixed/other Latinos (66.9%; p < 0.001). After adjusting for covariates, breastfeeding was associated with a 3.58% point increase in FEV1% predicted (p = 0.01) and a 21% reduction in asthma exacerbations (p = 0.03) in African Americans only.ConclusionBreastfeeding was associated with higher FEV1% predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.

Tibetan, one of the largest indigenous populations living in the high-altitude region of the Tibetan Plateau (TP), has developed a suite of physiological adaptation strategies to cope with the extreme highland environment in TP. Here, we reported genome-wide SNP data from 48 Kham-speaking Nagqu Tibetans and analyzed it with published data from 1,067 individuals in 167 modern and ancient populations to characterize the detailed Tibetan subgroup history and population substructure. Overall, the patterns of allele sharing and haplotype sharing suggested (1) the relatively genetic homogeny between the studied Nagqu Tibetans and ancient Nepalese as well as present-day core Tibetans from Lhasa, Nagqu, and Shigatse; and (2) the close relationship between our studied Kham-speaking Nagqu Tibetans and Kham-speaking Chamdo Tibetans. The fitted qpAdm models showed that the studied Nagqu Tibetans could be fitted as having the main ancestry from late Neolithic upper Yellow River millet farmers and deeply diverged lineages from Southern East Asians (represented by Upper Paleolithic Guangxi_Longlin and Laos_Hoabinhian), and a non-neglectable western Steppe herder-related ancestry (∼3%). We further scanned the candidate genomic regions of natural selection for our newly generated Nagqu Tibetans and the published core Tibetans via FST, iHS, and XP-EHH tests. The genes overlapping with these regions were associated with essential human biological functions such as immune response, enzyme activity, signal transduction, skin development, and energy metabolism. Together, our results shed light on the admixture and evolutionary history of Nagqu Tibetan populations.

Abstract Reintroductions are a powerful tool for the recovery of endangered species. However, their long‐term success is strongly influenced by the genetic diversity of the reintroduced population. The chances of population persistence can be improved by enhancing the population's adaptive ability through the mixing of individuals from different sources. However, where source populations are too diverse the reintroduced population could also suffer from outbreeding depression or unsuccessful admixture due to behavioural or genetic barriers. For the reintroduction of Asiatic wild ass Equus hemionus ssp. in Israel, a breeding core was created from individuals of two different subspecies (E. h. onager & E. h. kulan). Today the population comprises approximately 300 individuals and displays no signs of outbreeding depression. The aim of this study was a population genomic evaluation of this conservation reintroduction protocol. We used maximum likelihood methods and genetic clustering analyses to investigate subspecies admixture and test for spatial autocorrelation based on subspecies ancestry. Further, we analysed heterozygosity and effective population sizes in the breeding core prior to release and the current wild population. We discovered high levels of subspecies admixture in the breeding core and wild population, consistent with a significant heterozygote excess in the breeding core. Furthermore, we found no signs of spatial autocorrelation associated with subspecies ancestry in the wild population. Inbreeding and variance effective population size estimates were low. Our results indicate no genetic or behavioural barriers to admixture between the subspecies and suggest that their hybridization has led to greater genetic diversity in the reintroduced population. The study provides rare empirical evidence of the successful application of subspecies hybridization in a reintroduction. It supports use of intraspecific hybridization as a tool to increase genetic diversity in conservation translocations.

Population admixture results in genome-wide combinations of genetic variants derived from different ancestral populations of distinct ancestry, thus providing a unique opportunity for understanding the genetic determinants of phenotypic variation in humans. Here, we used whole-genome sequencing of 92 individuals with high coverage (30–60×) to systematically investigate genomic diversity in the Uyghurs living in Xinjiang, China (XJU), an admixed population of both European-like and East-Asian-like ancestry. The XJU population shows greater genetic diversity, especially a higher proportion of rare variants, compared with their ancestral source populations, corresponding to greater phenotypic diversity of XJU. Admixture-induced functional variants in EDAR were associated with the diversity of facial morphology in XJU. Interestingly, the interaction of functional variants between SLC24A5 and OCA2 likely influences the diversity of skin pigmentation. Notably, selection has seemingly been relaxed or canceled in several genes with significantly biased ancestry, such as HERC2 – OCA2. Moreover, signatures of post-admixture adaptation in XJU were identified, including genes related to metabolism (e.g. CYP2D6), digestion (e.g. COL11A1), olfactory perception (e.g. ANO2) and immunity (e.g. HLA). Our results demonstrated population admixture as a driving force, locally or globally, in shaping human genetic and phenotypic diversity as well as in adaptive evolution. [ABSTRACT FROM AUTHOR]

Background In recent decades, considerable attention has been paid to exploring the population genetic characteristics of Han Chinese, mainly documenting a north-south genetic substructure. However, the central Han Chinese have been largely underrepresented in previous studies. Aim To infer a comprehensive understanding of the homogenisation process and population history of Han Chinese. Subjects and methods We collected samples from 122 Han Chinese from seven counties of Hubei province in central China and genotyped 534,000 genome-wide SNPs. We compared Hubei Han with both ancient and present-day Eurasian populations using Principal Component Analysis, ADMIXTURE, f statistics, qpWave and qpAdm. Results We observed Hubei Han Chinese are at a genetically intermediate position on the north-south Han Chinese cline. We have not detected any significant genetic substructure in the studied groups from seven different counties. Hubei Han show significant evidence of genetic admixture deriving about 63% of ancestry from Tai-Kadai or Austronesian-speaking southern indigenous groups and 37% from Tungusic or Mongolic related northern populations. Conclusions The formation of Han Chinese has involved extensive admixture with Tai-Kadai or Austronesian-speaking populations in the south and Tungusic or Mongolic speaking populations in the north. The convenient transportation and central location of Hubei make it the key region for the homogenisation of Han Chinese.

Marianne Rodrigues Fernandes,1,2 Juliana Carla Gomes Rodrigues,1 Olalla Maroñas,3 Ana Latorre-Pellicer,3,4 Raquel Cruz,5 João Farias Guerreiro,6 Rommel Mario Rodriguez Burbano,1,2 Paulo Pimentel de Assumpção,1 Andrea Ribeiro-dos-Santos,1,6 Sidney Emanuel Batista dos Santos,1,6 Angel Carracedo,3,5,7 Ney Pereira Carneiro dos Santos1 1Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil; 2Departamento de ensino e pesquisa, Hospital Ophir Loyola, Belém, Pará, Brazil; 3Grupo de Medicina Xenómica, Centro Nacional de Genotipado (CEGEN-PRB3), Universidade de Santiago de Compostela, Santiago de Compostela, España; 4Unidad de Genética Clínica y Genómica Funcional, Departamento de Farmacología-Fisiología, Escuela de Medicina, Universidad de Zaragoza, IIS-Aragón, E-50009 Zaragoza, España; 5Centro de Investigación Biomédica en Enfermedades Raras (CIBERER), Grupo de Medicina Genómica, CIMUS, Universidad de Santiago de Compostela, Santiago de Compostela, España; 6Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém, Pará, Brazil; 7Fundación Pública de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Universidade de Santiago de Compostela, Santiago de Compostela, EspañaCorrespondence: Ney Pereira Carneiro dos SantosHospital Universitário João de Barros Barreto, Núcleo de Pesquisa em Oncologia, 2º Floor of the Unidade de Alta Complexidade em Oncologia. Av. Mundurucus, 4487, Guamá, Belém 66073-005, PA, BrazilTel +55 (91) 99113-9221Email npcsantos.ufpa@gmail.comIntroduction: The genetic admixture of the Brazilian population has considerable relevance to the implementation of the principles of pharmacogenomics (PGx), as it may compromise the extrapolation of data obtained in more homogeneous world populations.Purpose: This study aims to investigate a panel of 117 polymorphisms in 35 pharmacogenes, which contains label recommendations or clinical evidence by international drug regulatory agencies, in Amazonian Native American populations, and compare the results obtained with continental population data from the 1000 Genomes Project Consortium.Patients and Methods: The study population is composed of 109 Native American individuals from three Brazilian Amazon groups. The genotyping of the PGx polymorphisms was performed by allelic discrimination using TaqMan® OpenArray Genotyping with a panel of 120 customized assays on the QuantStudio™ 12K Flex Real-Time PCR System.Results: Statistical differences within the Native American populations were observed regarding both genotypes and phenotypes of some genes of the CYP family. The discriminant analysis of principal components (DAPCs) between the NAM group and the continental populations of the 1000 Genomes Project resulted in the clustering of the three Native American populations. Additionally, in general, the NAM group was determined to be closely situated between East Asia, America, and South Asia groups, which enabled us to infer a genetic similarity between these populations. The DAPC analysis further demonstrated that eight polymorphisms and six polymorphisms were more relevant in differentiating the NAM from the continental populations and the NAM populations among themselves, respectively.Conclusion: Some investigated polymorphisms show differences among world populations, particularly with populations of European origin, for whom precision medicine protocols are primarily designed. The accumulated knowledge regarding these variations may assist in the design of specific protocols for Native American populations and populations admixed with them.Keywords: Native Americans, pharmacogenomics, polymorphisms, population, genetic admixture, Brazil

A large number of species of Cordia (Boraginaceae) are found across the tropical and subtropical parts of the planet. Cordia species are mentioned in popular medicine as being used to cure a variety of ailments affecting a variety of human organs. Population genetic structure, genetic diversity, and phenotypic variation are unknown for this species in Iran. For this reason, we collected morphological as well as molecular data on this plant species, which is significant in its own right. We employed 70 plants that were randomly picked from seven geographical communities spread throughout four provinces to conduct our research. These populations' genetic diversity variables were analyzed. The results of the structure and K-Means grouping analyses indicated the existence of five distinct gene pools in the nation, which were isolated from one another geographically. Genetic and geographical separation were shown to be correlated using the Mantel analysis. Among communities, AMOVA found considerable genetic differences, with within-population variance accounting for around 55% of the overall genetic variability. Upcoming breeding and conservation efforts for this vital medicinal plant in the nation may benefit from these findings. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Excess risks of type 2 diabetes in UK South Asians (SA) and African Caribbeans (AC) compared with Europeans remain unexplained. We studied risks and determinants of type 2 diabetes in first- and second-generation (born in the UK) migrants, and in those of mixed ethnicity. Methods: Data from the UK Biobank, a population-based cohort of ~500,000 participants aged 40–69 at recruitment, were used. Type 2 diabetes was assigned using self-report and HbA1c. Ethnicity was both self-reported and genetically assigned using admixture level scores. European, mixed European/South Asian (MixESA), mixed European/African Caribbean (MixEAC), SA and AC groups were analysed, matched for age and sex to enable comparison. In the frames of this cross-sectional study, we compared type 2 diabetes in second- vs first-generation migrants, and mixed ethnicity vs non-mixed groups. Risks and explanations were analysed using logistic regression and mediation analysis, respectively. Results: Type 2 diabetes prevalence was markedly elevated in SA (599/3317 = 18%) and AC (534/4180 = 13%) compared with Europeans (140/3324 = 4%). Prevalence was lower in second- vs first-generation SA (124/1115 = 11% vs 155/1115 = 14%) and AC (163/2200 = 7% vs 227/2200 = 10%). Favourable adiposity (i.e. lower waist/hip ratio or BMI) contributed to lower risk in second-generation migrants. Type 2 diabetes in mixed populations (MixESA: 52/831 = 6%, MixEAC: 70/1045 = 7%) was lower than in comparator ethnic groups (SA: 18%, AC: 13%) and higher than in Europeans (4%). Greater socioeconomic deprivation accounted for 17% and 42% of the excess type 2 diabetes risk in MixESA and MixEAC compared with Europeans, respectively. Replacing self-reported with genetically assigned ethnicity corroborated the mixed ethnicity analysis. Conclusions/interpretation: Type 2 diabetes risks in second-generation SA and AC migrants are a fifth lower than in first-generation migrants. Mixed ethnicity risks were markedly lower than SA and AC groups, though remaining higher than in Europeans. Distribution of environmental risk factors, largely obesity and socioeconomic status, appears to play a key role in accounting for ethnic differences in type 2 diabetes risk. [ABSTRACT FROM AUTHOR]

Background Mongolian populations are widely distributed geographically, showing abundant ethnic diversity with geographic and tribal differences. Aim To infer the genetic substructure, admixture and ancient genetic sources of Mongolians together with Kazakhs Subjects and methods We genotyped more than 690,000 genome-wide SNPs from 33 Mongolian and Chinese Kazakh individuals and compared these with both ancient and present-day Eurasian populations using Principal Component Analysis (PCA), ADMIXTURE, Refine-IBD, f statistics, qpWave and qpAdm. Results We found genetic substructures within Mongolians corresponding to Ölöd, Chahar, and Inner Mongolian clusters, which was consistent with tribe classifications. Mongolian and Kazakh groups derived about 6–40% of West Eurasian related ancestry, most likely from Bronze Age Steppe populations. The East Asian related ancestry in Mongolian and Kazakh groups was well represented by the Neolithic DevilsCave related nomadic lineage, comprising 42–64% of studied groups. We also detected 10–51% of Han Chinese related ancestry in Mongolian and Kazakh groups, especially in Inner Mongolians. The average admixture times for Inner Mongolian, Mongolian_Chahar, Mongolian_Ölöd and Chinese Kazakh were about 1381, 626, 635 and 632 years ago, respectively, with Han and French as the sources. Conclusion The DevilsCave related ancestry was once widespread westwards covering a wide geographical range from Far East Russia to the Mongolia Plateau. The formation of present-day Mongolic and Turkic-speaking populations has also received genetic influence from agricultural expansion.

Abstract Background Avocado is an important cash crop in Tanzania, however its genetic diversity is not thoroughly investigated. This study was undertaken to explore the genetic diversity of avocado in the southern highlands using microsatellite markers. A total of 226 local avocado trees originating from seeds were sampled in eight districts of the Mbeya, Njombe and Songwe regions. Each district was considered as a population. The diversity at 10 microsatellite loci was investigated. Results A total of 167 alleles were detected across the 10 loci with an average of 16.7 ± 1.3 alleles per locus. The average expected and observed heterozygosity were 0.84 ± 0.02 and 0.65 ± 0.04, respectively. All but two loci showed a significant deviation from the Hardy-Weinberg principle. Analysis of molecular variance showed that about 6% of the variation was partitioned among the eight geographic populations. Population FST pairwise comparisons revealed lack of genetic differentiation for the seven of 28 population pairs tested. The principal components analysis (PCA) and hierarchical cluster analysis showed a mixing of avocado trees from different districts. The model-based STRUCTURE subdivided the trees samples into four major genetic clusters. Conclusion High diversity detected in the analysed avocado germplasm implies that this germplasm is a potentially valuable source of variable alleles that might be harnessed for genetic improvement of this crop in Tanzania. The mixing of avocado trees from different districts observed in the PCA and dendrogram points to strong gene flow among the avocado populations, which led to population admixture revealed in the STRUCTURE analysis. However, there is still significant differentiation among the tree populations from different districts that can be utilized in the avocado breeding program.

Cardiometabolic affections greatly contribute to the global burden of disease. The susceptibility to obesity, cardiovascular disease, and type-2 diabetes, conditions that add to the cardiometabolic syndrome (CMS), was associated with the ancestral genetic composition and gut microbiota. Studies explicitly testing associations between genetic ancestry and gut microbes are growing. We here examined whether the host genetic ancestry was associated with gut microbiota composition, and distinguished the effects of genetic ancestry and non-genetic factors on human cardiometabolic health. We performed a cross-sectional study with 441 community-dwelling Colombian mestizos from five cities spanning the Andes, Pacific, and Caribbean coasts. We characterized the host genetic ancestry by genotyping 40 ancestry informative markers; characterized gut microbiota through 16S rRNA gene sequencing; assessed diet intake, physical activity, cigarette, and medicament consumption; and measured cardiometabolic outcomes that allowed calculating a CMS risk scale. On average, each individual of our cohort was 67 ± 6% European, 21 ± 5% Native American and 12 ± 5% African. Multivariable-adjusted generalized linear models showed that individuals with higher Native American and African ancestries had increased fasting insulin, body mass index and CMS risk, as assessed by the CMS risk scale. Furthermore, we identified 21 OTUs associated to the host genetic ancestry and 20 to cardiometabolic health. While we highlight novel associations between genetic ancestry and gut microbiota, we found that the effect of intestinal microbes was more likely to explain the variance in CMS risk scale than the contributions of European, Native American and African genetic backgrounds.

Polygenic scores (PGSs) summarize the combined effect of common risk variants and are associated with breast cancer risk in patients without identifiable monogenic risk factors. One of the most well-validated PGSs in breast cancer to date is PGS 313 , which was developed from a Northern European biobank but has shown attenuated performance in non-European ancestries. We further investigate the generalizability of the PGS 313 for American women of European (EA), African (AFR), Asian (EAA), and Latinx (HL) ancestry within one institution with a singular electronic health record (EHR) system, genotyping platform, and quality control process. We found that the PGS 313 achieved overlapping areas under the receiver operator characteristic (ROC) curve (AUCs) in females of HL (AUC = 0.68, 95% confidence interval [CI] = 0.65-0.71) and EA ancestry (AUC = 0.70, 95% CI = 0.69-0.71) but lower AUCs for the AFR and EAA populations (AFR: AUC = 0.61, 95% CI = 0.56-0.65; EAA: AUC = 0.64, 95% CI = 0.60-0.680). While PGS 313 is associated with hormone-receptor-positive (HR+) disease in EA Americans (odds ratio [OR] = 1.42, 95% CI = 1.16-1.64), this association is lost in African, Latinx, and Asian Americans. In summary, we found that PGS 313 was significantly associated with breast cancer but with attenuated accuracy in women of AFR and EAA descent within a singular health system in Los Angeles. Our work further highlights the need for additional validation in diverse cohorts prior to the clinical implementation of PGSs., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Manchu is the third-largest ethnic minority in China and has the largest population size among the Tungusic-speaking groups. However, the genetic origin and admixture history of the Manchu people are far from clear due to the sparse sampling and a limited number of markers genotyped. Here, we provided the first batch of genome-wide data of genotyping approximate 700,000 single-nucleotide polymorphisms (SNPs) in 93 Manchu individuals collected from northeast China. We merged the newly generated data with data of publicly available modern and ancient East Asians to comprehensively characterize the genetic diversity and fine-scale population structure, as well as explore the genetic origin and admixture history of northern Chinese Manchus. We applied both descriptive methods of ADMIXTURE, fineSTRUCTURE, F ST , TreeMix, identity by decedent (IBD), principal component analysis (PCA), and qualitative f -statistics (f 3, f 4, qpAdm, and qpWave). We found that Liaoning Manchus have a close genetic relationship and significant admixture signal with northern Han Chinese, which is in line with the cluster patterns in the haplotype-based results. Additionally, the qpAdm-based admixture models showed that modern Manchu people were formed as major ancestry related to Yellow River farmers and minor ancestry linked to ancient populations from Amur River Bain, or others. In summary, the northeastern Chinese Manchu people in Liaoning were an exception to the coherent genetic structure of Tungusic-speaking populations, probably due to the large-scale population migrations and genetic admixtures in the past few hundred years. [ABSTRACT FROM AUTHOR]

Sui people, which belong to the Tai-Kadai-speaking family, remain poorly characterized due to a lack of genome-wide data. To infer the fine-scale population genetic structure and putative genetic sources of the Sui people, we genotyped 498,655 genome-wide single-nucleotide polymorphisms (SNPs) using SNP arrays in 68 Sui individuals from seven indigenous populations in Guizhou province and Guangxi Zhuang Autonomous Region in Southwest China and co-analyzed with available East Asians via a series of population genetic methods including principal component analysis (PCA), ADMIXTURE, pairwise Fst genetic distance, f -statistics, qpWave , and qpAdm. Our results revealed that Guangxi and Guizhou Sui people showed a strong genetic affinity with populations from southern China and Southeast Asia, especially Tai-Kadai- and Hmong-Mien-speaking populations as well as ancient Iron Age Taiwan Hanben, Gongguan individuals supporting the hypothesis that Sui people came from southern China originally. The indigenous Tai-Kadai-related ancestry (represented by Li), Northern East Asian-related ancestry, and Hmong-Mien-related lineage contributed to the formation processes of the Sui people. We identified the genetic substructure within Sui groups: Guizhou Sui people were relatively homogeneous and possessed similar genetic profiles with neighboring Tai-Kadai-related populations, such as Maonan. While Sui people in Yizhou and Huanjiang of Guangxi might receive unique, additional gene flow from Hmong-Mien-speaking populations and Northern East Asians, respectively, after the divergence within other Sui populations. Sui people could be modeled as the admixture of ancient Yellow River Basin farmer-related ancestry (36.2–54.7%) and ancient coastal Southeast Asian-related ancestry (45.3–63.8%). We also identified the potential positive selection signals related to the disease susceptibility in Sui people via integrated haplotype score (iHS) and number of segregating sites by length (nSL) scores. These genomic findings provided new insights into the demographic history of Tai-Kadai-speaking Sui people and their interaction with neighboring populations in Southern China. [ABSTRACT FROM AUTHOR]

The Hui people are unique among Chinese ethnic minorities in that they speak the same language as Han Chinese (HAN) but practice Islam. However, as the second-largest minority group in China numbering well over 10 million, the Huis are under-represented in both global and regional genomic studies. Here, we present the first whole-genome sequencing effort of 234 Hui individuals (NXH) aged over 60 who have been living in Ningxia, where the Huis are mostly concentrated. NXH are genetically more similar to East Asian than to any other global populations. In particular, the genetic differentiation between NXH and HAN (F ST = 0.0015) is only slightly larger than that between northern and southern HAN (F ST = 0.0010), largely attributed to the western ancestry in NXH (∼10%). Highly differentiated functional variants between NXH and HAN were identified in genes associated with skin pigmentation (e.g. SLC24A5), facial morphology (e.g. EDAR), and lipid metabolism (e.g. ABCG8). The Huis are also distinct from other Muslim groups such as the Uyghurs (F ST = 0.0187), especially, NXH derived much less western ancestry (∼10%) compared with the Uyghurs (∼50%). Modeling admixture history indicated that NXH experienced an episode of two-wave admixture. An ancient admixture occurred ∼1,025 years ago, reflecting the intensive west–east contacts during the late Tang Dynasty, and the Five Dynasties and Ten Kingdoms period. A recent admixture occurred ∼500 years ago, corresponding to the Ming Dynasty. Notably, we identified considerable sex-biased admixture, that is, excess of western males and eastern females contributing to the NXH gene pool. The origins and the genomic diversity of the Hui people imply the complex history of contacts between western and eastern Eurasians. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae is the causative agent of gonorrhea, a sexually transmitted infection (STI) of major importance. As a result of antibiotic resistance, there are now limited options for treating patients. We collected draft genome sequence data and associated metadata data on 76 N. gonorrhoeae strains from around the globe and searched for known determinants of antibiotics resistance within the strains. The population structure and evolutionary forces within the pathogen population were analyzed. Our results indicated a cosmopolitan gonoccocal population mainly made up of five subgroups. The estimated ratio of recombination to mutation (r/m = 2.2) from our data set indicates an appreciable level of recombination occurring in the population. Strains with resistance phenotypes to more recent antibiotics (azithromycin and cefixime) were mostly found in two of the five population subgroups.

BackgroundChildhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest.ObjectiveTo determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children.MethodsWe analyzed 5493 Latinos with and without asthma from 3 independent studies. For each participant, we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry.ResultsNative American ancestry was associated with lower odds of asthma (OR = 0.72, 95% CI: 0.66-0.78, P = 8.0 × 10(-15)), while African ancestry was associated with higher odds of asthma (OR = 1.40, 95% CI: 1.14-1.72, P = .001). These associations were robust to adjustment for covariates related to early life exposures, air pollution, and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of FEV1 (-77 ± 19 mL; P = 5.8 × 10(-5) and -83 ± 19 mL; P = 1.1 x 10(-5), respectively) and forced vital capacity (-100 ± 21 mL; P = 2.7 × 10(-6) and -107 ± 22 mL; P = 1.0 x 10(-6), respectively).ConclusionDifferences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos.

Genetic diversity studies are essential to understand the conservation and management of plant resources in any environment. The genus Consolida (DC.) Gray (Ranuculaceae) belongs to tribe Delphinieae. It comprises approximately 52 species, including the members of the genus Aconitella Spach. No detailed Random Amplified Polymorphic DNA (RAPD) studies were conducted to study Consolida genetic diversity. Therefore, we collected and analyzed 19 species from 12 provinces of regions. Overall, one hundred and twenty-seven plant specimens were collected. We showed significant differences in quantitative morphological characters in plant species. Unweighted pair group method with arithmetic mean and principal component analysis (PCA) divided Consolida species into two groups. All primers produced polymorphic amplicons though the extent of polymorphism varied with each primer. The primer OPA-06 was found to be most powerful and efficient as it generated a total of 24 bands of which 24 were polymorphic. The Mantel test showed correlation (r = 0.34, p=0.0002) between genetic and geographical distances. We reported high genetic diversity, which clearly shows the Consolida species can adapt to changing environments since high genetic diversity is linked to species adaptability. Present results highlighted the utility of RAPD markers and morphometry methods to investigate genetic diversity in Consolida species. Our aims were 1) to assess genetic diversity among Consolida species 2) is there a correlation between species genetic and geographical distance? 3) Genetic structure of populations and taxa.