Abstract Recently, several studies on the Uruguayan population have shown that it is formed by unequal contributions from Europeans, Africans, Native Americans, and others. The native component is larger when maternal contribution is analyzed, but its ethnic/geographic origin remains unclear, as it is also unclear how and when these groups arrived. To contribute to the knowledge about prehistoric and historic peopling of the territory and its relations with other populations, 32 complete mitochondrial genomes (mitogenomes) were obtained by next generation sequencing. They belong to present inhabitants of the country, whose hypervariable regions were previously analyzed and whose identified haplogroups belonged to one of the four main haplogroups of Native American origin. Seven new subhaplogroups (A2be, A2bf, B2an, C1d1h, C1b30, C1b31 and D1x) were determined, another was redenominated (C1d1d - present C1d1g), and the criteria to assign B2b6 and D1g5 were reviewed. The age of the new subhaplogroups was estimated between 4.554 and 11.985 years, while the age of C1d1g was estimated in 20.736 years. Some sequences could be related to different ethnic groups, or to several geographic regions such as Amazonia, Chaco, Pampa or Andes. The new subhaplogroup assignations, together with their geographic distribution and chronology, are discussed in relation to the general panorama of South America.

Resumen Recientemente, diversos estudios sobre la población uruguaya han demostrado que está conformada por desiguales aportes de europeos, africanos y pueblos originarios, entre otros. El aporte indígena es mayor cuando se analiza la contribución por línea materna, aunque su origen étnico/geográfico no es claro, ni tampoco cuándo ni cómo llegaron los distintos grupos. Para aportar al conocimiento del poblamiento prehistórico e histórico del territorio y sus relaciones con otras poblaciones se analizan, por secuenciación masiva, 32 genomas mitocondriales completos (mitogenomas) de habitantes actuales del país, identificados previamente por sus regiones hipervariables como correspondientes a los cuatro haplogrupos principales de origen americano. Se determinaron siete nuevos subhaplogrupos (A2be, A2bf, B2an, C1d1h, C1b30, C1b31 y D1x), otro se redenominó (C1d1d - actual C1d1g) y se plantea la revisión de los criterios de asignación de B2b6 y D1g5. Se estimó la antigüedad de los subhaplogrupos nuevos, que varía entre 4554 y 11985 años, con la excepción de C1d1g, cuya edad fue estimada en 20736 años. Algunas secuencias pudieron ser vinculadas a distintos grupos étnicos o a diversas regiones geográficas, como Amazonia, Chaco, Pampa, o Andes. Se discuten las nuevas asignaciones de subhaplogrupos y las de algunos previamente definidos, así como su distribución geográfica y antigüedad, con relación al panorama general de América del Sur.

ABSTRACT Several genetic studies have demonstrated that Uruguayan peoples are a trihybrid population, deriving from European/Mediterranean, Native American, and African ancestries that vary by region within the country. Studies on ancestries and origins that focus on Montevideo, the capital of Uruguay, are scarce and may differ from a general country-wide sample. We investigated the genetic origin of the population of Montevideo using a sample derived from a previously published study, in which we examined different factors that could influence ancestry estimations. The sample consisted of 269 women (cases and controls from a breast cancer research study). Haplogroups and hypervariable regions of the mitochondrial DNA, as well as nuclear ancestry informative markers, were analyzed. Differences in ancestral contributions were found when analyzing women attending public hospitals compared to those attending private clinics, with significant differences between Native American and European/Mediterranean contributions. After adjusting for health care system, we estimated the following contributions for the overall population of Montevideo: 24.6 % Native American, 67.7 % European, and 7.7 % African for maternal inheritance, and 11.1 % Native American, 81.4 % European, and 7.5 % African for biparental inheritance. We focused in particular on Native American and African contributions, and the results were discussed considering other sources of evidence. Due to the differences found between subsamples, caution is advised about sampling strategies and reference values to be used in further population studies.

RESUMEN Diversos estudios genéticos han demostrado que la población uruguaya es trihíbrida, formada por europeo/mediterráneos, indígenas y africanos, cuyo aporte varía en distintas regiones del país. Pese a que Montevideo es la capital de la República, hay escasos estudios sobre los orígenes de su población, que pueden diferir de otras regiones. En este trabajo se propone indagar sobre estos orígenes a partir de información genética en una muestra derivada de una previamente publicada, profundizando en algunas características para determinar su posible influencia en la estimación de la ancestría. Se consideró una muestra de 269 mujeres (casos y controles de un estudio de cáncer de mama) en quienes se analizaron haplogrupos y secuencias de las regiones hipervariables del ADN mitocondrial (ADNmt) y marcadores individuales de ancestría (AIMs) del ADN nuclear. Se observó que había diferencias en los porcentajes de ancestría cuando se analizaban separadamente las personas que se atendían en el sistema público de salud en relación a las que lo hacían en el sistema mutual, con diferencias significativas para el aporte indígena y el europeo/mediterráneo. Luego de corregidos los valores por lugar de atención de salud, se estimaron los siguientes aportes: 24.6% indígena, 67,7% europeo/mediterráneo y 7,7% africano para herencia materna, y de 11,1% indígena, 81,4% europeo/mediterráneo, y 7,5% africano para la herencia biparental. Se analizaron particularmente los aportes indígena y africano y se discutieron los resultados con relación a otros estudios. Debido a las diferencias encontradas relacionadas con la heterogeneidad de la población montevideana, se alerta sobre el muestreo y valores de referencia para estudios poblacionales futuros.

Abstract Genome-wide association studies focused on searching genes responsible for several diseases. Admixture mapping studies proposed a more efficient alternative capable of detecting polymorphisms contributing with a small effect on the disease risk. This method focuses on the higher values of linkage disequilibrium in admixed populations. To test this, we analyzed 10 genomic regions previously defined as related with colorectal cancer among nine populations and studied the variation pattern of haplotypic structures and heterozygosity values on seven categories of SNPs. Both analyses showed differences among chromosomal regions and studied populations. Admixed Latin-American samples generally show intermediate values. Heterozygosity of the SNPs grouped in categories varies more in each gene than in each population. African related populations have more blocks per chromosomal region, coherently with their antiquity. In sum, some similarities were found among Latin American populations, but each chromosomal region showed a particular behavior, despite the fact that the study refers to genes and regions related with one particular complex disease. This study strongly suggests the necessity of developing statistical methods to deal with di- or tri-hybrid populations, as well as to carefully analyze the different historic and demographic scenarios, and the different characteristics of particular chromosomal regions and evolutionary forces.