Search

Background: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. - Objectives: To conduct a GWAS for facial skin ageing and mole count in adults

BackgroundA strong association between the proportion of Native American 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 Native American people in Chile. We set out to investigate the causal association between Native American Mapuche ancestry and GBC risk, and the possible mediating effects of gallstone disease and body mass index (BMI) on this association.MethodsMarkers of Mapuche ancestry were selected based on the informativeness for assignment measure and then used as instrumental variables in two-sample mendelian randomization (MR) analyses and complementary sensitivity analyses.ResultWe found evidence of a causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% for every 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.6×10-5). Mapuche ancestry was also causally linked to gallstone disease (IVW risk increase of 3.6% per 1% increase in Mapuche proportion, 95% CI 3.1% to 4.0%, p = 1.0×10-59), suggesting a mediating effect of gallstones in the relationship between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative causal effect on BMI (IVW estimate -0.006 kg/m2 per 1% increase in Mapuche proportion, 95% CI -0.009 to -0.003, p = 4.4×10-5).ConclusionsThe results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between Mapuche ancestry and GBC risk previously noted in observational studies appears to be causal, primary and secondary prevention strategies that take into account the individual proportion of Mapuche ancestry could be particularly efficient.

We report a genome-wide association study for facial features in > 6,000 Latin Americans. We placed 106 landmarks on 2D frontal photographs using the cloud service platform Face++. After Procrustes superposition, genome-wide association testing was performed for 301 inter-landmark distances. We detected nominally significant association (P-value − 8) for 42 genome regions. Of these, 9 regions have been previously reported in GWAS of facial features. In follow-up analyses, we replicated 26 of the 33 novel regions (in East Asians or Europeans). The replicated regions include 1q32.3, 3q21.1, 8p11.21, 10p11.1, and 22q12.1, all comprising strong candidate genes involved in craniofacial development. Furthermore, the 1q32.3 region shows evidence of introgression from archaic humans. These results provide novel biological insights into facial variation and establish that automatic landmarking of standard 2D photographs is a simple and informative approach for the genetic analysis of facial variation, suitable for the rapid analysis of large population samples.

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04–1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.

Here we evaluate the accuracy of prediction for eye, hair and skin pigmentation in a dataset of > 6500 individuals from Mexico, Colombia, Peru, Chile and Brazil (including genome-wide SNP data and quantitative/categorical pigmentation phenotypes - the CANDELA dataset CAN). We evaluated accuracy in relation to different analytical methods and various phenotypic predictors. As expected from statistical principles, we observe that quantitative traits are more sensitive to changes in the prediction models than categorical traits. We find that Random Forest or Linear Regression are generally the best performing methods. We also compare the prediction accuracy of SNP sets defined in the CAN dataset (including 56, 101 and 120 SNPs for eye, hair and skin colour prediction, respectively) to the well-established HIrisPlex-S SNP set (including 6, 22 and 36 SNPs for eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a world-wide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the prediction of categorical pigmentation traits for forensic purposes in Latin America, while illustrating the impact of training datasets on its accuracy. Fil: Palmal, Sagnik. Centre National de la Recherche Scientifique; Francia. Aix-Marseille Université; Francia Fil: Kaustubh Adhikari. The Open University; Reino Unido. University College London; Estados Unidos Fil: Mendoza Revilla, Javier. Universidad Peruana Cayetano Heredia; Perú. Institut Pasteur de Paris.; Francia Fil: Fuentes Guajardo, Macarena. Universidad de Tarapacá; Chile Fil: Silva de Cerqueira, Caio Cesar. Scientific Police of São Paulo State; Brasil Fil: Bonfante, Betty. Aix-Marseille Université; Francia. Centre National de la Recherche Scientifique; Francia Fil: Chacón Duque, Juan Camilo. Natural History Museum; Reino Unido Fil: Sohail, Anood. Kinnaird College for Women. Department of Biotechnology; Pakistán Fil: Hurtadeo, Malena. Universidad Peruana Cayetano Heredia; Perú Fil: Villegas, Valeria. Universidad Peruana Cayetano Heredia; Perú Fil: Granja, Vanessa. Universidad Peruana Cayetano Heredia; Perú Fil: Jaramillo, Claudia. Kinnaird College for Women. Department of Biotechnology; Pakistán. Universidad de Antioquia; Colombia Fil: Arias, Williams. Universidad de Antioquia; Colombia Fil: Barquera Lozano, Rodrigo. Instituto Nacional de Antropología e Historia; México. Max Planck Institute for the Science of Human History. Department of Archaeogenetics; Alemania Fil: Everardo Martínez, Paola. Instituto Nacional de Antropología e Historia; México Fil: Gómez Valdés, Jorge. Instituto Nacional de Antropología e Historia; México Fil: Villamil Ramirez, Hugo. Universidad Nacional Autónoma de México; México Fil: Hünemeier, Tábita. Universidade de Sao Paulo; Brasil Fil: Ramallo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina. Universidade Federal do Rio Grande do Sul; Brasil Fil: Parolin, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; Argentina Fil: Gonzalez, Rolando Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Schüler-Faccini, Lavinia. Universidade Federal do Rio Grande do Sul, Porto Alegre; Brasil Fil: Bortolini, María Cátira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Acuña Alonzo, Victor. Instituto Nacional de Antropología e Historia; México. Universidade Federal do Rio Grande do Sul; Brasil Fil: Canizales Quinteros, Samuel. Universidad Nacional Autónoma de México; México Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú Fil: Bedoya, Gabriel. Universidad de Antioquia; Colombia Fil: Rothhammer, Francisco. Universidad de Tarapacá; Chile. Universidad de Chile; Chile Fil: Balding, David. University College London; Reino Unido. University of Melbourne; Australia Fil: Faux, Pierre. Aix-Marseille Université; Francia. Centre National de la Recherche Scientifique; Francia Fil: Ruiz Linares, Andrés. Aix-Marseille Université; Francia. Centre National de la Recherche Scientifique; Francia. University College London; Reino Unido. Fudan University; República de China

Recent advancement from low-throughput sequencing techniques to high-throughput sequencing gives the public more efficient ways to acquire human adaptive immune receptor repertoire sequences (AIRR-seq). The advanced high-throughput sequencing techniques allow scientists to comprehensively examine and characterize the T cell receptors’ and B cell receptors’ genetic sequences efficiently. The development of multi-powerful platforms in AIRR-seq studies and advanced bioinformatic tools also boosts the AIRR community’s richness. However, although high-throughput sequencing technologies have been well-developed, most AIRR-seq studies have not taken ancestries or populations in their research into consideration. In the study, we investigate the ancestry distribution in the T cell receptor sequencing(TCR-seq) studies to initial estimate the ancestry distribution in the open AIRR-seq studies. The result disclosed that 84.08% of the studies with reported ancestries are conducted under European ancestries, which omit other populational ancestries’ diversity in the open TCR-Seq studies.

We carried out a genome-wide association study in Latin Americans and identified novel face morphology loci.., To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.

With the advent of high-throughput sequencing technologies, the fields of immunogenomics and adaptive immune receptor repertoire research are facing both opportunities and challenges. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become an increasingly important tool to characterize T and B cell responses in settings of interest. However, the majority of AIRR-seq studies conducted so far were performed in individuals of European ancestry, restricting the ability to identify variation in human adaptive immune responses across populations and limiting their applications. As AIRR-seq studies depend on the ability to assign VDJ sequence reads to the correct germline gene segments, efforts to characterize the genomic loci that encode adaptive immune receptor genes in different populations are urgently needed. The availability of comprehensive germline gene databases and further applications of AIRR-seq studies to individuals of non-European ancestry will substantially enhance our understanding of human adaptive immune responses, promote the development of effective diagnostics and treatments, and eventually advance precision medicine., 22 pages,1 table

We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair and eye color, HIrisPlex-S has a similar performance to the CANDELA-specific prediction SNP sets. However, for skin pigmentation the performance of HIrisPlex-S is markedly lower than the SNP set defined here, including predictions in an independent dataset of Native American data. These results reflect the relatively high variation in hair and eye color among Europeans for whom HIrisPlex-S was developed, whereas their variation in skin pigmentation is comparatively lower. Furthermore, we show that the dataset used in the training of prediction models strongly impacts on the portability of these models across Europeans and Native Americans.

Objectives: To investigate the variation in dental nonmetric traits and to evaluate the utility of this variation for inferring genetic ancestry proportions in a sample of admixed Latin Americans.; Materials and Methods: We characterized a sample from Colombia (N = 477) for 34 dental traits and obtained estimates of individual Native American, European, and African ancestry using genome‐wide SNP data. We tested for correlation between dental traits, genetic ancestry, age, and sex. We carried out a biodistance analysis between the Colombian sample and reference continental population samples using the mean measure of divergence statistic calculated from dental trait frequencies. We evaluated the inference of genetic ancestry from dental traits using a regression approach (with 10‐fold cross‐validation) as well as by testing the correlation between estimates of ancestry obtained from genetic and dental data.; Results: Latin Americans show intermediate dental trait frequencies when compared to Native Americans, Europeans, and Africans. Significant correlations were observed for several dental traits, genetic ancestry, age, and sex. The biodistance analysis displayed a closer relationship of Colombians to Europeans than to Native Americans and Africans. Mean ancestry estimates obtained from the dental data are similar to the genetic estimates (Native American: 32% vs. 28%, European: 59% vs. 63%, and African: 9% vs. 9%, respectively). However, dental features provided low predictive power for genetic ancestry of individuals in both approaches tested (R2, Facultad de Ciencias Naturales y Museo

Objectives: The scoring and analysis of dental nonmetric traits are predominantly accomplished by using the Arizona State University Dental Anthropology System (ASUDAS), a standard protocol based on strict definitions and three‐dimensional dental plaques. However, visual scoring, even when controlled by strict definitions of features, visual reference, and the experience of the observer, includes an unavoidable part of subjectivity. In this methodological contribution, we propose a new quantitative geometric morphometric approach to quickly and efficiently assess the variation of shoveling in modern human maxillary central incisors (UI1).\ud \ud Materials and methods: We analyzed 87 modern human UI1s by means of virtual imaging and the ASU‐UI1 dental plaque grades using geometric morphometrics by placing semilandmarks on the labial crown aspect. The modern human sample was composed of individuals from Europe, Africa, and Asia and included representatives of all seven grades defined by the ASUDAS method.\ud \ud Results: Our results highlighted some limitations in the use of the current UI1 ASUDAS plaque, indicating that it did not necessarily represent an objective gradient of expression of a nonmetric tooth feature. Rating of shoveling tended to be more prone to intra‐ and interobserver bias for the highest grades. In addition, our analyses suggest that the observers were strongly influenced by the depth of the lingual crown aspect when assessing the shoveling.\ud \ud Discussion: In this context, our results provide a reliable and reproducible framework reinforced by statistical results supporting the fact that open scale numerical measurements can complement the ASUDAS method.

Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs. Fil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; Alemania Fil: Marcelain, Katherine. Universidad de Chile; Chile Fil: Barahona Ponce, Carol. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; Chile Fil: Baez Benavides, Pablo F.. Universidad de Chile; Chile Fil: Müller, Bettina. Instituto Nacional del Cáncer, Chile; Chile Fil: de Toro, Gonzalo. Hospital Puerto Montt; Chile Fil: Retamales, Javier. Instituto Nacional del Cáncer, Chile; Chile Fil: Barajas, Olga. Hospital Clinico de la Universidad de Chile; Chile. Universidad de Chile; Chile Fil: Ahumada, Monica. Hospital Clínico de la Universidad de Chile; Chile. Universidad de Chile; Chile Fil: Morales, Erik. Regional Hospital; Chile Fil: Rojas, Armando. Universidad Catolica de Maule; Chile Fil: Sanhueza, Verónica. Hospital Padre Hurtado; Chile Fil: Loader, Denisse. Hospital Padre Hurtado; Chile Fil: Rivera, María Teresa. Hospital del Salvador; Chile Fil: Gutiérrez, Lorena. Hospital San Juan de Dios, Santiago de Chile; Chile Fil: Bernal, Giuliano. Universidad Católica del Norte; Chile Fil: Ortega, Alejandro. Hospital Regional, Arica; Chile Fil: Montalvo, Domingo. Hospital Regional de Arica Doctor Juan Noé Crevani; Chile Fil: Portiño, Sergio. Hospital Clinico de la Universidad de Chile; Chile Fil: Bertrán, Maria Enriqueta. Ministerio de Salud, Valdivia; Chile Fil: Gabler, Fernando. Universidad de Santiago de Chile. Hospital Clinico San Borja Arriaran; Chile Fil: Spencer, Loreto. Hospital Regional de Concepción - Dr. Guillermo Grant Benavente; Chile Fil: Olloquequi, Jordi. Universidad Autónoma de Chile; Chile Fil: González Silos, Rosa. Ruprecht Karls Universitat Heidelberg; Alemania Fil: Fischer, Christine. Ruprecht Karls Universitat Heidelberg; Alemania Fil: Scherer, Dominique. Ruprecht Karls Universitat Heidelberg; Alemania Fil: Jenab, Mazda. International Agency for Research on Cancer; Francia Fil: Aleksandrova, Krasimira. Universitat Potsdam; Alemania Fil: Katzke, Verena. German Cancer Research Center; Alemania Fil: Gonzalez-jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Weiderpass, Elisabete. International Agency for Research on Cancer; Francia Fil: Moradi, Tahereh. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Fischer, Krista. University of Tartu; Estonia Fil: Bossers, Willem. Lifelines Cohort Study; Países Bajos Fil: Brenner, Hermann. German Cancer Research Center; Alemania Fil: Hveem, Kristian. Norges Teknisk naturvitenskapelige Universitet; Noruega Fil: Eklund, Niina. National Institute For Health And Welfare; Finlandia Fil: Völker, Uwe. Universitätsmedizin Greifswald; Alemania Fil: Waldenberger, Melanie. Helmholtz Center Munich German Research Center For Environmental Health; Alemania Fil: Fuentes Guajardo, Macarena. Universidad de Tarapaca.; Chile Fil: Bedoya, Gabriel. Universidad de Antioquia; Colombia Fil: Bortolini, Maria C.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Canizales, Samuel. Universidad Nacional Autónoma de México; México Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Ruiz Linares, Andres. Fudan University; China Fil: Rothhammer, Francisco. Universidad de Tarapaca.; Chile Fil: Lorenzo Bermejo, Justo. Ruprecht Karls Universitat Heidelberg; Alemania

Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies performed on the same samples, indicating the action of different genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes. Fil: Quinto Sanchez, Mirsha Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Muñoz-Muñoz, Francesc. Universidad Nacional Autónoma de México; México Fil: Gomez-Valdes, Jorge. Universitat Autònoma de Barcelona; España Fil: Cintas, Celia. Instituto Nacional de Antropologia E Historia, Mexico; México Fil: Navarro, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Cerqueira, Caio Cesar Silva De. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Paschetta, Carolina Andrea. Equipe de Perícias Criminalísticas de Ourinhos; Fil: de Azevedo, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Ramallo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Acuña-Alonzo, Victor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Adhikari, Kaustubh. Colegio Universitario de Londres; Reino Unido Fil: Fuentes-Guajardo, MacArena. Instituto Nacional de Antropologia E Historia, Mexico; México Fil: Hünemeier, Tábita. Colegio Universitario de Londres; Reino Unido Fil: Everardo, Paola. Universidad de Tarapaca de Arica; Chile Fil: De Avila, Francisco. Colegio Universitario de Londres; Reino Unido Fil: Jaramillo, Claudia. Universidade de Sao Paulo; Brasil Fil: Arias, Williams. Instituto Nacional de Antropologia E Historia, Mexico; México Fil: Gallo, Carla. Universidad Nacional Autónoma de México; México Fil: Poletti, Giovani. Instituto Nacional de Antropologia E Historia, Mexico; México Fil: Bedoya Berrío, Gabriel. Universidad de Antioquia; Colombia Fil: Bortolini, Maria Catira. Universidad de Antioquia; Colombia Fil: Canizales-Quinteros, Samuel. Universidad Peruana Cayetano Heredia; Perú Fil: Rothhammer, Francisco. Universidad Peruana Cayetano Heredia; Perú Fil: Rosique, Javier. Universidad de Antioquia; Colombia Fil: Ruiz-Linares, Andres. Universidade Federal do Rio Grande do Sul; Brasil Fil: González José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina

Resumen: A pesar del esfuerzo realizado por numerosos investigadores, el conocimiento existente acerca del origen de la mayoría de los pue- blos originarios chilenos continúa siendo fragmentario y parcialmente contradictorio. En consecuencia nos hemos propuesto como objetivo contribuir al esclarecimiento de este importante aspecto de la historia del pueblo chileno, ofreciendo un enfoque desde la perspectiva de la genética histórica. Examinamos, en primer lugar, la variación que presentan los haplogrupos pan-americanos de ADN mitocondrial (A, B, C y D) de poblaciones actuales de cinco regiones naturales de Chile continental: Norte Grande, Norte Chico, Zona Central, Zona Sur y Zona Austral. Al evaluar la distribución de hombres y mujeres de origen ancestral americano se observa una predominancia de mujeres sobre hombres, contrastando este hecho con la distribución de géneros en el grupo de origen europeo, donde se observa consistentemente predominancia del sexo masculino. Luego calculamos distancias genéticas entre representantes de diferentes grupos originarios del cono sur, las regiones naturales de Chile y poblaciones mixtas de Brasil, Bolivia, Perú y Argentina. Las distancias genéticas obtenidas indican, como era de esperar, proximidad genética entre los pueblos quechua, aimara, y atacameño y el Norte Grande y entre pehuenches, mapuches, huilliches, tehuelches, alacalufes, yaganes y onas y la Zona Sur y Austral y sugieren desplazamientos y mezcla poblacional de grupos de la Amazonia, los Andes Centrales, Chile y Argentina, que tomados en conjunto, contribuyen a entender con mayor claridad el origen geográfico de los grupos étnicos chilenos.

The history of the Americas involved the encounter of millions of Native Americans, Europeans, and Africans. A variable admixture of these three continental groups has taken place throughout the continent, influenced by demography and a range of social factors. This variable admixture has had a major influence on the genetic makeup of populations across the continent. Here, we summarize the demographic history of the region, highlight some social factors that affected historical admixture, and review major patterns of ancestry across the Western Hemisphere based on genetic data.

espanolResumen: A pesar del esfuerzo realizado por numerosos investigadores, el conocimiento existente acerca del origen de la mayoria de los pue- blos originarios chilenos continua siendo fragmentario y parcialmente contradictorio. En consecuencia nos hemos propuesto como objetivo contribuir al esclarecimiento de este importante aspecto de la historia del pueblo chileno, ofreciendo un enfoque desde la perspectiva de la genetica historica. Examinamos, en primer lugar, la variacion que presentan los haplogrupos pan-americanos de ADN mitocondrial (A, B, C y D) de poblaciones actuales de cinco regiones naturales de Chile continental: Norte Grande, Norte Chico, Zona Central, Zona Sur y Zona Austral. Al evaluar la distribucion de hombres y mujeres de origen ancestral americano se observa una predominancia de mujeres sobre hombres, contrastando este hecho con la distribucion de generos en el grupo de origen europeo, donde se observa consistentemente predominancia del sexo masculino. Luego calculamos distancias geneticas entre representantes de diferentes grupos originarios del cono sur, las regiones naturales de Chile y poblaciones mixtas de Brasil, Bolivia, Peru y Argentina. Las distancias geneticas obtenidas indican, como era de esperar, proximidad genetica entre los pueblos quechua, aimara, y atacameno y el Norte Grande y entre pehuenches, mapuches, huilliches, tehuelches, alacalufes, yaganes y onas y la Zona Sur y Austral y sugieren desplazamientos y mezcla poblacional de grupos de la Amazonia, los Andes Centrales, Chile y Argentina, que tomados en conjunto, contribuyen a entender con mayor claridad el origen geografico de los grupos etnicos chilenos. EnglishAbstract: Despite efforts made by numerous researchers, existing knowledge about the origin of the majority of Chilean ethnic populations continues to be fragmentary and partially contradictory. Our aim is to contribute to the clarification of this important aspect of Chilean history, from the perspective of historical genetics. We first examine the variation of pan-American haplogroups of mitochondrial DNA (A, B, C and D) in five natural regions of continental Chile: Norte Grande (Far North), Norte Chico (Near North), Central Zone, Southern Zone and Southernmost Zone. When evaluating the distribution of men and women of American ancestral origin, the predominance of women over men is noticeable. In contrast, when the gender distribution of individuals of European ancestral origin is analyzed, male predominance is consistently observed. Next we calculated genetic distances between representatives of different ethnic groups of the southern cone of South America, the natural regions of Chile and mixed populations of Brazil, Bolivia, Peru and Argentina. As expected, genetic distances indicate proximity between Quechua, Aymara, and Atacameno and the Norte Grande, and between Pehuenche, Mapuche, Huilliche, Tehuelche, Alacalufe, Yagan and Ona and the Southern and Southernmost Zone. In addition, displacements of groups and population mixing involving the Amazon, Central Andes and Argentina are revealed, contributing to a clearer understanding of the geographical origin of Chilean ethnic groups.

Background: Studies performed in Andean populations living in high altitude, indicate that the reduced availability of oxygen could be associated to both a fetal growth retardation and a lower birth weight. These variables are predictive of morbidity and mortality during the first year of life. Aim: To study perinatal variables of newborns of mothers living at contrasting altitudinal levels, harboring different degrees of Aymara ancestry. Subjects and Methods: Review of medical records of 5295 women whose deliveries occurred between February 2004 and August 2010. Information was obtained on place of residence, grouped into two categories: coast (150 to 3,000 m) and high plateau (3.000 to 4.300 m), ancestry was estimated using number of Aymara surnames that were homologated to percentages of Amerindian admixture, gestational age, birth weight, height, head circumference and obstetric variables. Results: Gestational age showed a tendency to increase and birth weight, height and head circumference to decrease with altitude of residence. Only weight reached statistical significance. Women with Aymara ancestry gave birth to children with a significantly higher gestational age, weight and cranial circumference. Conclusions: Altitude of residence is related to a decrease in perinatal variables that proved to be less pronounced in newborns of mothers with a higher degree of Aymara ancestry. Results suggest a genetic adaptation to hypoxia that could be related to candidate genes linked to the capture, transport or utilization of oxygen.

Latin Americans arguably represent the largest recently admixed populations in the world. This reflects a history of massive settlement by immigrants (mostly Europeans and Africans) and their variable admixture with Natives, starting in 1492. This process resulted in the population of Latin America showing an extensive genetic and phenotypic diversity. Here we review how genetic analyses are being applied to examine the demographic history of this population, including patterns of mating, population structure and ancestry. The admixture history of Latin America, and the resulting extensive diversity of the region, represents a natural experiment offering an advantageous setting for genetic association studies. We review how recent analyses in Latin Americans are contributing to elucidating the genetic architecture of human complex traits.

Background: Amerindian admixture is an important parameter to consider in epidemiological studies in American countries, to make a proper selection of cases and controls. Aim: To compare Amerindian admixture estimates obtained using ABO*A and ABO*O blood group alleles and ancestral identity markers (AIMs) in the mixed Chilean population. Subjects and Methods: Amerindian admixture rates were determined in 720 Chilean volunteers residing in Arica and born in the 15 regions of the country, using ABO*O and ABO*A alleles and 40 AIMs selected from more than 500,000 single nucleotide polymorphisms (SNPs). Results: Mean admixture estimates obtained using ABO*O and ABO*A alleles and AIMs were 35, 47% and 48% respectively. There was concordance in estimates, with the exception of the admixture based on ABO*O allele and AIMs. Conclusions: In Chile, Amerindian admixture estimates obtained using ABO*A could be used as an alternative to AIMs in justified cases provided the sample size is reasonably large.

Amerindian admixture is an important parameter to consider in epidemiological studies in American countries, to make a proper selection of cases and controls.To compare Amerindian admixture estimates obtained using ABO*A and ABO*O blood group alleles and ancestral identity markers (AIMs) in the mixed Chilean population.Amerindian admixture rates were determined in 720 Chilean volunteers residing in Arica and born in the 15 regions of the country, using ABO*O and ABO*A alleles and 40 AIMs selected from more than 500,000 single nucleotide polymorphisms (SNPs).Mean admixture estimates obtained using ABO*O and ABO*A alleles and AIMs were 35, 47% and 48% respectively. There was concordance in estimates, with the exception of the admixture based on ABO*O allele and AIMs.In Chile, Amerindian admixture estimates obtained using ABO*A could be used as an alternative to AIMs in justified cases provided the sample size is reasonably large.

Studies performed in Andean populations living in high altitude, indicate that the reduced availability of oxygen could be associated to both a fetal growth retardation and a lower birth weight. These variables are predictive of morbidity and mortality during the first year of life.To study perinatal variables of newborns of mothers living at contrasting altitudinal levels, harboring different degrees of Aymara ancestry.Review of medical records of 5,295 women whose deliveries occurred between February 2004 and August 2010. Information was obtained on place of residence, grouped into two categories: coast (150 to 3,000 m) and high plateau (3,000 to 4,300 m), ancestry was estimated using number of Aymara surnames that were homologated to percentages of Amerindian admixture, gestational age, birth weight, height, head circumference and obstetric variables.Gestational age showed a tendency to increase and birth weight, height and head circumference to decrease with altitude of residence. Only weight reached statistical significance. Women with Aymara ancestry gave birth to children with a significantly higher gestational age, weight and cranial circumference.Altitude of residence is related to a decrease in perinatal variables that proved to be less pronounced in newborns of mothers with a higher degree of Aymara ancestry. RESULTS suggest a genetic adaptation to hypoxia that could be related to candidate genes linked to the capture, transport or utilization of oxygen.

The children of related parents show increased risk of early mortality. The Native American genome typically exhibits long stretches of homozygosity, and Latin Americans are highly heterogeneous regarding the individual burden of homozygosity, the proportion and the type of Native American ancestry. We analysed nationwide mortality and genome-wide genotype data from admixed Chileans to investigate the relationship between common causes of child mortality, homozygosity and Native American ancestry. Results from two-stage linear-Poisson regression revealed a strong association between the sum length of runs of homozygosity (SROH) above 1.5 Megabases (Mb) in each genome and mortality due to intracranial non-traumatic haemorrhage of foetus and newborn (5% increased risk of death per Mb in SROH, P = 1 × 10−3) and disorders related to short gestation and low birth weight (P = 3 × 10−4). The major indigenous populations in Chile are Aymara–Quechua in the north of the country and the Mapuche–Huilliche in the south. The individual proportion of Aymara–Quechua ancestry was associated with an increased risk of death due to anencephaly and similar malformations (P = 4 × 10−5), and the risk of death due to Edwards and Patau trisomy syndromes decreased 4% per 1% Aymara–Quechua ancestry proportion (P = 4 × 10−4) and 5% per 1% Mapuche–Huilliche ancestry proportion (P = 2 × 10−3). The present results suggest that short gestation, low birth weight and intracranial non-traumatic haemorrhage mediate the negative effect of inbreeding on human selection. Independent validation of the identified associations between common causes of child death, homozygosity and fine-scale ancestry proportions may inform paediatric medicine. Fil: Koenigstein, Fabienne. Ruprecht Karls Universitat Heidelberg; Alemania Fil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; Alemania Fil: Wilson, James F.. University of Edinburgh; Reino Unido Fil: Fuentes Guajardo, Macarena. Universidad de Tarapacá; Chile Fil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Bedoya Berrío, Gabriel. Universidad de Antioquia; Colombia Fil: Bortolini, Maria Cátira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Acuña Alonzo, Victor. Instituto Nacional de Antropología e Historia. Escuela Nacional de Antropología e Historia; México Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Ruiz-Linares, Andres. Fudan University; China. Aix-Marseille Université; Francia. Centre National de la Recherche Scientifique; Francia. University College London; Reino Unido Fil: Rothhammer, Francisco. Universidad de Tarapaca. Instituto de Alta Investigación; Chile Fil: Lorenzo Bermejo, Justo. Ruprecht Karls Universitat Heidelberg; Alemania