RESUMEN
Admixture is a fundamental evolutionary process that has influenced genetic patterns in numerous species. Maximum-likelihood approaches based on allele frequencies and linkage-disequilibrium have been extensively used to infer admixture processes from genome-wide data sets, mostly in human populations. Nevertheless, complex admixture histories, beyond one or two pulses of admixture, remain methodologically challenging to reconstruct. We developed an Approximate Bayesian Computation (ABC) framework to reconstruct highly complex admixture histories from independent genetic markers. We built the software package MetHis to simulate independent SNPs or microsatellites in a two-way admixed population for scenarios with multiple admixture pulses, monotonically decreasing or increasing recurring admixture, or combinations of these scenarios. MetHis allows users to draw model-parameter values from prior distributions set by the user, and, for each simulation, MetHis can calculate numerous summary statistics describing genetic diversity patterns and moments of the distribution of individual admixture fractions. We coupled MetHis with existing machine-learning ABC algorithms and investigated the admixture history of admixed populations. Results showed that random forest ABC scenario-choice could accurately distinguish among most complex admixture scenarios, and errors were mainly found in regions of the parameter space where scenarios were highly nested, and, thus, biologically similar. We focused on African American and Barbadian populations as two study-cases. We found that neural network ABC posterior parameter estimation was accurate and reasonably conservative under complex admixture scenarios. For both admixed populations, we found that monotonically decreasing contributions over time, from Europe and Africa, explained the observed data more accurately than multiple admixture pulses. This approach will allow for reconstructing detailed admixture histories when maximum-likelihood methods are intractable.
Asunto(s)
Genética de Población , Modelos Genéticos , Programas Informáticos , África , Negro o Afroamericano/genética , Algoritmos , Barbados , Teorema de Bayes , Biología Computacional , Simulación por Computador , Europa (Continente) , Variación Genética , Humanos , Funciones de Verosimilitud , Aprendizaje Automático , Repeticiones de Microsatélite , Polimorfismo de Nucleótido SimpleRESUMEN
We evaluated the performance of three PGx panels to estimate biogeographical ancestry: the DMET panel, and the VIP and Preemptive PGx panels described in the literature. Our analysis indicate that the three panels capture quite well the individual variation in admixture proportions observed in recently admixed populations throughout the Americas, with the Preemptive PGx and DMET panels performing better than the VIP panel. We show that these panels provide reliable information about biogeographic ancestry and can be used to guide the implementation of PGx clinical decision-support (CDS) tools. We also report that using these panels it is possible to control for the effects of population stratification in association studies in recently admixed populations, as exemplified with a warfarin dosing GWA study in a sample from Brazil.
Asunto(s)
Genoma Humano/genética , Polimorfismo de Nucleótido Simple/genética , Américas , Brasil , Genética de Población/métodos , Estudio de Asociación del Genoma Completo/métodos , Humanos , Farmacogenética/métodosRESUMEN
Cuba is the most populated country in the Caribbean and has a rich and heterogeneous genetic heritage. Here, we take advantage of dense genomic data from 860 Cuban individuals to reconstruct the genetic structure and ancestral origins of this population. We found distinct admixture patterns between and within the Cuban provinces. Eastern provinces have higher African and Native American ancestry contributions (average 26% and 10%, respectively) than the rest of the Cuban provinces (average 17% and 5%, respectively). Furthermore, in the Eastern Cuban region, we identified more intense sex-specific admixture patterns, strongly biased towards European male and African/Native American female ancestries. Our subcontinental ancestry analyses in Cuba highlight the Iberian population as the best proxy European source population, South American and Mesoamerican populations as the closest Native American ancestral component, and populations from West Central and Central Africa as the best proxy sources of the African ancestral component. Finally, we found complex admixture processes involving two migration pulses from both Native American and African sources. Most of the inferred Native American admixture events happened early during the Cuban colonial period, whereas the African admixture took place during the slave trade and more recently as a probable result of large-scale migrations from Haiti.
Asunto(s)
Demografía , Genética de Población , Cuba , Femenino , Pool de Genes , Variación Genética , Hispánicos o Latinos/genética , Migración Humana , Humanos , Masculino , Factores de TiempoRESUMEN
A genome is a mosaic of chromosome fragments from ancestors who existed some arbitrary number of generations earlier. Here, we reconstruct the genome of Hans Jonatan (HJ), born in the Caribbean in 1784 to an enslaved African mother and European father. HJ migrated to Iceland in 1802, married and had two children. We genotyped 182 of his 788 descendants using single-nucleotide polymorphism (SNP) chips and whole-genome sequenced (WGS) 20 of them. Using these data, we reconstructed 38% of HJ's maternal genome and inferred that his mother was from the region spanned by Benin, Nigeria and Cameroon.
Asunto(s)
Población Negra/genética , Personas Esclavizadas , Genoma Humano , Haploidia , Linaje , Composición Familiar/historia , Estudio de Asociación del Genoma Completo/métodos , Historia del Siglo XVIII , Humanos , Islandia , Masculino , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodos , Migrantes , Indias OccidentalesRESUMEN
The transatlantic slave trade was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations. Throughout the Americas, thousands of enslaved Africans managed to escape captivity and establish lasting communities, such as the Noir Marron. We find that this population has the highest proportion of African ancestry (â¼98%) of any African-descendant population analyzed to date, presumably because of centuries of genetic isolation. By contrast, African-descendant populations in Brazil and Colombia harbor substantially more European and Native American ancestry as a result of their complex admixture histories. Using ancestry tract-length analysis, we detect different dates for the European admixture events in the African-Colombian (1749 CE; confidence interval [CI]: 1737-1764) and African-Brazilian (1796 CE; CI: 1789-1804) populations in our dataset, consistent with the historically attested earlier influx of Africans into Colombia. Furthermore, we find evidence for sex-specific admixture patterns, resulting from predominantly European paternal gene flow. Finally, we detect strong genetic links between the African-descendant populations and specific source populations in Africa on the basis of haplotype sharing patterns. Although the Noir Marron and African-Colombians show stronger affinities with African populations from the Bight of Benin and the Gold Coast, the African-Brazilian population from Rio de Janeiro has greater genetic affinity with Bantu-speaking populations from the Bight of Biafra and west central Africa.
Asunto(s)
Población Negra/genética , África , Brasil , Femenino , Guyana Francesa , Flujo Génico/genética , Genética de Población , Estudio de Asociación del Genoma Completo/métodos , Haplotipos , Hispánicos o Latinos/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Suriname , Población Blanca/genéticaRESUMEN
Seventeen Y-chromosomal short tandem repeats (STRs) were analyzed in 347 healthy, unrelated, autochthonous males from the Andalusian provinces of Huelva (N=167) and Granada (N=180). AmpFlSTR Y-filer PCR Amplification kit (Applied Biosystems) was used to type the Y-STR markers. A total of 156 and 166 different haplotypes for the 17 Y-STR set were detected in Huelva, and Granada, respectively. The same haplotype diversity was found for both samples (0.998±0.001), and the overall discrimination capacity was 0.904. The most common minimal haplotype (DYS19, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393) in both subpopulations was 14-13-16-24-11-13-13, which is also the most frequent haplotype among Atlantic European populations. Comparison analysis using pairwise R(ST) values and Analysis of Molecular Variance (AMOVA) revealed a significant genetic distance between our Andalusian samples and other ones from the northern Iberian fringe (including Basque and Pyrenean populations). However, results from the multi-dimensional scaling analysis (MDS) yielded a well-defined group of Iberian populations separated from the other Mediterranean clusters observed.