Resumen Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. Métodos: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. Resultados: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. Conclusiones: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Abstract Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. Methods: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. Results: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. Conclusions: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

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.

Resumen La población uruguaya ha sido tradicionalmente considerada como carente de indígenas. En 1996 se comenzaron a recabar datos sobre “etnia o raza” y se incluyó como pregunta en el Censo de 2011. En este, un 2,4% de la población reconoció como ancestría principal la indígena, y el 5,1% declaró tener ancestros indígenas, diferentemente de lo observado al estudiar ancestría genética materna o autosómica (35% y 14% de aporte indígena, respectivamente). Esta situación es similar en otros países de la región, cuyos datos serán brevemente discutidos. Se analizarán también los hechos que pudieron conducir a la invisibilización de los indígenas y sus descendientes, como su ubicación geográfica y nivel socioeconómico. En particular, se considerará el género de quienes pasaron a formar parte de la sociedad nacional y la falta de voz de las mujeres durante un largo período, puesto que fueron mujeres indígenas quienes mayoritariamente se integraron a la sociedad nacional.

Resumo A população uruguaia é tradicionalmente considerada “sem índios”. Passados quase 150 anos, em 1996 a população passou a ser questionada sobre “etnia ou raça”, pergunta finalmente incluida no Censo 2011. Neste, 2,4% da população reconhecia o indígena como a ancestralidade principal e 5,1% declaravam ter ancestrais indígenas, diferentemente do que foi observado ao estudar a ancestralidade genética materna ou autossômica (35 e 14% de contribuição indígena, respectivamente). Esta situação é semelhante em outros países da região, cujos dados serão brevemente discutidos. Também serão analisados os fatos que podem levar à invisibilidade dos indígenas e seus descendentes, como sua localização geográfica e nível socioeconômico. Em particular, será considerado o gênero daqueles que se tornaram parte da sociedade nacional, e a falta de voz das mulheres por um longo período, uma vez que foram as mulheres indígenas as que mais se integraram à sociedade nacional.

Abstract The Uruguayan population has traditionally been considered “without Indians.” After almost 150 years, in 1996 the population began to be questioned about “ethnicity or race”, included in the 2011 Census questions. In this, 2.4% of the population recognized the indigenous as the main ancestry, and 5.1% declared having indigenous ancestors, differently from what was observed when studying maternal or autosomal genetic ancestry (35 and 14% of indigenous contribution, respectively). This situation is similar in other countries of the region, whose data will be briefly discussed. The facts that could lead to the invisibility of the indigenous people and their descendants, such as their geographical location and socioeconomic level, will also be analyzed. In particular, the gender of those who became part of the national society will be considered, and the lack of voice of women for a long period, since it was indigenous women who were mostly integrated into the national society.

ABSTRACT Recently we published the analysis of surnames of the 2010 Electoral Register of República Oriental del Uruguay through calculation of isonymic distances, based on the 19 departments of the country, and the 171 possible comparisons, showing two large clusters in the south, and a few others with smaller relationships in the north and east. The purpose of the present work is to deepen the analysis of isonymic distances using the distribution of surnames based on the 221 municipalities, instead of departments, that make up the country. Isonymic distances were estimated taking two at a time, for 24,310 comparisons. Matrices of isonymic distances were tested for correlation with geographic distance. The correlations were higher (r=0.253±0.033) for euclidean, intermediate for Lasker (r=0.18±0.029), and lower for Nei’s distance (r=0.17±0.03), all statistically significant (p<0.001). New dendrograms were constructed with clusters not previously determined. The relative surname homogeneity in the south is noteworthy, with 7 clusters close to Montevideo. In the north, with 8 clusters identified, distances are greater, revealing more surname heterogeneity. It was confirmed that the Río Negro acted as a geographical barrier, but orographic, hydrographic, historic, and sociodemographic factors, which were not detected in the previous analysis, were also involved. Finally, the usefulness of surnames in the analysis of the population structure of a whole country, in this case Uruguay, was highlighted.

RESUMEN Recientemente publicamos el análisis de los apellidos del Padrón Electoral de 2010 de la República Oriental del Uruguay a través de distancias isonímicas, basado en sus 19 departamentos y las 171 comparaciones posibles entre estos, lo que mostró la formación de dos grandes agrupamientos en el sur, y otros pocos vinculados en el norte y este. El objetivo del presente trabajo es detallar el análisis de las distancias isonímicas utilizando la distribución de apellidos, no a nivel departamental, sino de los 221 municipios en los cuales se divide el país. Se estimaron las distancias isonímicas entre ellos, tomados dos a dos (24.310 comparaciones), se construyeron las matrices de distancia correspondientes y se correlacionaron con las de distancias geográficas. La correlación fue mayor para la distancia euclídea (r=0,253 ± 0,033), intermedia para la de Lasker (r=0,18 ±0,029) y menor para la de Nei (r=0,17±0,03), todas estadísticamente significativas (p<0,001). Se construyeron nuevos dendrogramas determinándose agrupamientos no identificados previamente. Se destaca cierta homogeneidad en el sur con las menores distancias, con 7 agrupamientos cercanos a Montevideo. Al norte, con mayores distancias que denotan mayor heterogeneidad de apellidos, se identifican 8 agrupamientos. Se corrobora que el río Negro actuó como barrera geográfica, pero también se observan límites marcados por otros accidentes orográficos, hidrográficos, históricos y factores sociodemográficos no identificados en el análisis anterior. Por último, se resalta la utilidad del uso de apellidos para analizar la estructura poblacional, permitiendo el análisis global de la población de un país, en este caso, Uruguay.

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.

Resumen: La hemofilia A (HA) es la coagulopatía ligada al cromosoma X más frecuente. Es causada por mutaciones en el gen del factor VIII (FVIII) de coagulación (F8). La HA puede ser severa cuando la actividad del FVIII es menor a 1% (FVIII: C<1IU/dL). Casi la mitad de las HA severas son producidas por inversiones del F8, como la del intrón 1 (Inv1) y del intrón 22 (Inv22). Los pacientes con HA severa experimentan sus primeros sangrados generales entre los 9,7 - 10,9 meses, ocurriendo principalmente en las articulaciones. Se investigó la presencia de la Inv1 e Inv22 en la región noreste de Uruguay (departamentos de Tacuarembó, Rivera y Cerro Largo) para estimar su frecuencia y detectar la presencia de portadoras. Fueron estudiados 14 individuos (ocho pacientes con HA severa, cuatro madres y dos hermanas de pacientes) de cinco familias. La investigación de las inversiones se realizó aplicando las pruebas de inverse shifting-PCR (IS-PCR). La Inv1 se encontró en dos pacientes (hermanos) de Tacuarembó, en su hermana y madre (portadoras), mientras que un paciente de Rivera y su madre (portadora) resultaron positivos para la Inv22. Preliminarmente, en conjunto, la Inv1 y la Inv22 representan la causa de la HA severa en el 40% de las familias del noreste de Uruguay, valor menor a lo esperado; sin embargo, debido a la reducida población estudiada, la Inv1 muestra una frecuencia preliminar (20%, 1/5 familias, 25%, 2/8 pacientes) considerablemente mayor a estudios previos. Estos datos permiten caracterizar la etiología genética de la hemofilia, la detección de las portadoras, conocer la distribución geográfica de las mutaciones y el asesoramiento genético.

Summary: Hemophilia A (HA) is the most common X-linked coagulopathy, it is caused by mutations in the coagulation factor VIII (FVIII) gene (F8). HA can be severe when the FVIII activity is less than 1% (FVIII: C <1IU / dL). Almost a half of the severe HAs are produced by inversions of F8, the intron 1 (Inv1) and intron 22 (Inv22). Patients with severe HA show their first general bleeding between 9.7 - 10.9 months, mainly in the joints. We researched the presence of Inv1 and Inv22 in the Northeast region of Uruguay (Departments: Tacuarembó, Rivera and Cerro Largo) to estimate their frequency and detect the presence of carriers. We studied 14 individuals in 5 different families (8 patients with severe HA, 4 mothers and 2 sisters of patients). The inversion study was carried out using inverse shifting-PCR (IS-PCR) tests. Inv1 was found in 2 patients (siblings) from Tacuarembó, in their sister and mother (carriers). A patient from Rivera and his mother (carrier) were positive for Inv22. Inv1 and Inv22 are the cause of severe HA in 40% of the patients in North East of Uruguay, less than expected; however, due to the reduced population studied, Inv1 shows a considerably higher frequency than previous studies. These data enable us to characterize the genetic etiology of hemophilia, to adequately monitor patients, detect carriers, the geographical distribution of mutations and the corresponding genetic counseling for families.

Resumo: A hemofilia A (HA) é a coagulopatia ligada ao cromossomo X mais frequente, causada por mutações no gene do fator VIII (FVIII) de coagulação (FVIII) (F8). A HA pode ser grave quando a atividade do FVIII é menor que 1% (FVIII: C <1IU / dL). Quase metade da HA grave é produzida por inversões de F8, como a do Íntron 1 (Inv1) e do Íntron 22 (Inv22). Pacientes com HA grave experimentam seu primeiro sangramento geral entre 9,7 e 10,9 meses, principalmente nas articulações. A presença de Inv1 e Inv22 na região nordeste do Uruguai (departamentos: Tacuarembó, Rivera e Cerro Largo) foi investigada para estimar a sua frequência e detectar a presença de portadora. Foram estudados 14 indivíduos (8 pacientes com HA grave, 4 mães e 2 irmãs de pacientes) de 5 famílias. A pesquisa das inversões foi realizada aplicando os testes de inverse shifting -PCR (IS-PCR). Encontramos Inv1 em 2 pacientes (irmãos) de Tacuarembó, na sua irmã e mãe (portadoras), enquanto 1 paciente de Rivera e sua mãe (transportadora) foram positivos para Inv22. Preliminarmente, Inv1 e Inv22 juntos representam a causa de HA grave em 40% das famílias do nordeste do Uruguai, valor inferior ao esperado, no entanto, devido à pequena população estudada, Inv1 mostra uma frequência preliminar (20%, 1/5 famílias, 25%, 2/8 pacientes) consideravelmente mais alta que os estudos anteriores. Esses dados permitem-nos caracterizar a etiologia genética da hemofilia, detectar aos portadores, conhecer a distribuição geográfica das mutações e realizar aconselhamento genético.

CG14E01 "Isla Larga" is a site with a moundlike structure (cerrito de indios) located in Rocha (Uruguay), with a chronology spanning the period from 3600 years BP to the 17th century. Evidence of various interethnic interactions has been found at the site, namely, two Tupiguarani urns and some European glass beads. Connected with this evidence, three primary burials, one male and two female, were recovered. The goal of this paper is to analyze the complete mitochondrial genome of the female individuals, one of which shows perimortem trauma. The DNA of both individuals was extracted from teeth, and their mitochondrial genome sequence was obtained by means of highthroughput sequencing. The authenticity of the sequences was verified through the analysis of postmortem DNA damage in the mapped reads. Both individuals were found to belong to a previously unregistered haplotype of the founding American haplogroup C1b, sharing the mutations 185A, 3116T, 3203T, 14397G, and 14502C. In view of the considerations made by other researchers about the mounds as territorial markers, the possibility that this structure could have served as a burial location for individuals related by kinship gains strength. On the other hand, the elements of the context and the evidence of trauma allow a second perspective, related to the interethnic dynamics described in the regional ethnohistorical record.

CG14E01 "Isla Larga" es un sitio con estructura monticular ("cerrito de indios") localizado en el departamento de Rocha (Uruguay), con una cronología que se extiende de 3600 años AP al siglo XVII. En este sitio se registran evidencias vinculadas con diversos contactos interétnicos en la forma de dos urnas Tupiguaraní y cuentas de vidrio de origen europeo. Asociados a estas evidencias se recuperaron tres enterramientos primarios, uno masculino y dos femeninos. El objetivo de este trabajo consiste en analizar el mitogenoma completo de los individuos femeninos, uno de los cuales presenta trauma perimortem. El ADN de los dos individuos fue extraído a partir de piezas dentales y su secuencia genómica mitocondrial fue obtenida mediante secuenciación masiva, verificándose su autenticidad por el análisis de las modificaciones postmortem del ADN en las lecturas mapeadas. Ambos individuos pertenecen a un haplotipo hasta ahora no registrado del haplogrupo fundador americano C1b, y comparten las mutaciones 185A, 3116T, 3203T, 14397G y 14502C. En virtud de consideraciones hechas por otros investigadores a propósito del "cerrito" como marcador territorial, la posibilidad de que la estructura haya servido como lugar de inhumación para individuos unidos por lazos de parentesco es sugerente. Por otra parte, los elementos del contexto y la evidencia de trauma añaden una segunda perspectiva, vinculada con las dinámicas interétnicas descriptas en el registro etnohistórico de la región.

We present the analysis of subadult human remains recovered in the archaeofaunal assemblage of the site CH2D01-A. Located in the wetland of San Miguel (Rocha, Uruguay), this mound site is dated between 2090 ±90 and 220±50 years BP, and presents 17 human burials which were excavated. Later, 514 human remains were found in the faunal assemblage, 50 of which correspond to subadult individuals. These remains were integrated to the mortuary record of the site through the analysis of anatomical and taphonomic parameters, as well as using locational data. Twenty-two of the remains were assigned to the 2 previously defined child burials, and 28 were identified as belonging to 4 new individuals, with ages estimated from 2 to 16 years old. With this analysis, the minimum number of individuals represented increases to 21, as the number of subadults goes from 2 to 6, considerably expanding the subadult record of the site, which has a remarkably low frequency despite the relatively good preservation of the osteological remains. We emphasize the importance of a joint analysis of the bioarchaeological and archaeofaunal records as a means of improving the control of taphonomical factors related to record formation processes and methodological issues.

En este estudio se analizan los restos humanos de individuos subadultos identificados en el conjunto arqueofaunístico del sitio CH2D01-A. Se trata de un sitio monticular ubicado en el bañado de San Miguel (Rocha, Uruguay) en el que se identificaron ocupaciones con un rango temporal entre 2090±90 y 220±50 AP. Se recuperaron 17 enterramientos humanos individuales. Posteriormente se hallaron 514 restos humanos en el conjunto faunístico, de los cuales 50 corresponden a individuos subadultos. Dichos restos fueron integrados al registro funerario del sitio a través de parámetros anatómicos y tafonómicos e información locacional. Se asignaron 22 restos a dos entierros infantiles previamente definidos, en tanto que 28 restos fueron identificados como pertenecientes a cuatro nuevos individuos con edades comprendidas entre 2 y 16 años. Con este análisis aumenta a 21 el número mínimo de individuos representados y la cantidad de subadultos pasa de 2 a 6, incrementando un registro de subadultos reducido, considerando la buena preservación general de restos óseos en el sitio. Se enfatiza la importancia de los análisis conjuntos de los registros bioarqueológico y arqueofaunístico del Uruguay como forma de mejorar el control tafonómico de procesos de formación del registro y de factores metodológicos.

A general introduction to the origins and history of Latin American populations is followed by a systematic review of the data from molecular autosomal assessments of the ethnic/continental (European, African, Amerindian) ancestries for 24 Latin American countries or territories. The data surveyed are of varying quality but provide a general picture of the present constitution of these populations. A brief discussion about the applications of these results (admixture mapping) is also provided. Latin American populations can be viewed as natural experiments for the investigation of unique anthropological and epidemiological issues.

Hemoglobinopathies are the most common recessive diseases worldwide but their prevalence in Uruguay has not been investigated. In this study, 397 unrelated outpatient children from the Pereira Rosell Hospital Center (CHPR), as well as 31 selected patients with microcytic anemia and 28 β-thalassemia carriers were analyzed for hemoglobinopathies by using biochemical and molecular biology methods. Parametric and non-parametric methods were used to compare the hematological indices between groups of genotypes. Of the 397 patients in the first group, approximately 1% (0.76% HbS and 0.25% β-thalassemia) had a mutation in the HBB gene and 3.3% had α-thalassemia. These mutations had a heterogeneous distribution that varied according to individual ancestry. HbS was found exclusively in individuals with declared African ancestry and had a carrier frequency of 2.2%. The frequency of α-thalassemia carriers in outpatients of European and African ancestry was 1.2% and 6.5%, respectively. In contrast, the frequency of α-thalassemia carriers in patients with microcytic anemia was 25.8%, significantly higher (p < 0.01) than that observed in the sample as a whole and in Afro-descendants and Euro-descendants. Significant differences were observed in the hematological parameters between individuals with thalassemia genotypes and those with a normal genotype. These results indicate that hemoglobinopathies are a relevant health problem in Uruguay.

Hemoglobin Southampton (also known as hemoglobin Casper) is a rare hemoglobin structural variant resulting from a substitution of a leucine residue for proline at codon beta106 [beta106(G8)Leu→Pro, CTG→CCG]. It is very unstable and associated with severe hemolytic anemia. We detected this mutation in a 37-year-old Uruguayan woman with a history of severe chronic hemolytic anemia since her childhood. According to our knowledge this is the first time that this variant has been found in the Uruguayan population.

Indígenas, africanos e europeus conformaram, com contribuições desiguais, a população uruguaia. Dados censitários indicam que no inicio do século XIX o país tinha 36% de africanos e descendentes, enquanto a quantidade de indígenas não estava determinada. Posteriormente, os censos não incluem informação que se refira a origem, com exceção dos estrangeiros. Em 1996- 1997 a Pesquisa de Lares solicitou a auto-declaração de "raça", e em 2006, da ancestralidade. A primeira revela que 5,9 % da população se considerava "negra ou variáveis de mestiçagem com negros", e 0,4 %, indígena ou variáveis de mestiçagem com indígenas, enquanto que para a ancestralidade os valores subiam a 9,1 % e 4,5 % respectivamente. Os dados genéticos mostram aportes genéticos de 6% africano e 10% indígena, enquanto que a ancestralidade materna eleva estes valores a 10% e 31% respectivamente. Se discutem os dados censitários e genéticos no marco da identidade nacional.

Native Americans, Africans and Europeans formed, to varying degrees, the Uruguayan population. At the beginning of the 19 th century, census data indicated that the country was comprised of 36% African or African descended inhabitants, while the number of Natives was not determined. After this, there is no available information on the origins of the population, with the exception of foreigners. In 1996-1997, a Household Survey asked Uruguayans to self-identify their "race", and in 2006, their ancestry. The first survey showed that 5.9% of the populations was "black or mixed-black" and 0.4% was Native or Native-descended, while the percentages of individuals who claimed African or Native ancestry increased to 9.1% and 4.5% respectively. Genetic data demonstrate that there is a contribution of 6% of African and 10% of Native American blood in the population, while maternal ancestry increases these values to 10% and 31% respectively. Census and genetic data are discussed in relation to national identity.

Indígenas, africanos y europeos conformaron, con aportes desiguales, la población uruguaya. Datos censales indican que a comienzos del siglo XIX el país tenía 36% de africanos y sus descendientes, mientras la cantidad de indígenas no estaba determinada; posteriormente, los censos no incluyen información que se refiera al origen, a excepción de los nacidos en el extranjero. En 1996-1997, la Encuesta de Hogares solicitó la autodeclaración de "raza", y en 2006, la de ancestría. La primera arroja que 5,9% de la población se consideraba "negra o negra y sus mezclas", y 0,4%, "indígena y sus mezclas", mientras que para la ancestría los valores ascendían a 9,1% y 4,5% respectivamente. Los datos genéticos muestran aportes genéticos de 6% africano y 10% indígena, mientras que la ancestría materna sube estos valores a 10% y 31% respectivamente. Se discuten los datos censales y genéticos en el marco de la identidad nacional.

La asociación del alelo betaS que produce hemoglobina S (HbS) y de un alelo de beta talasemia (betatal), ocurre principalmente en poblaciones que tienen simultáneamente ascendencia africana y mediterránea, y provoca un síndrome drepanocítico denominado HbS-beta talasemia. Este síndrome presenta una gran heterogeneidad clínica y genética debida en gran parte al alelo talasémico presente. Los individuos que portan un alelo talasémico beta0 presentan, en general, un curso clínico similar a los homocigotas para el alelo betaS de la HbS. En cambio, los que portan un alelo beta+ presentan un curso clínico variable, dependiendo de la reducción en la síntesis de cadena de beta globina. En este estudio se describe el caso clínico de dos pacientes con HbS-beta talasemia que consultaron en el Centro Hemato-Oncológico Pediátrico del Hospital Pereira Rossell. Se analizó el genotipo de los dos pacientes por medio de secuenciación automática del gen de la beta globina. Se demostró la presencia del alelo talasémico beta+ IVS-1-110 G->A en uno de los pacientes y del alelo beta0 codón39 C->T en el otro paciente, por lo cual ambos son heterocigotos compuestos betaS/betatal. Se discute la relación entre los datos clínicos y paraclínicos con los resultados del diagnóstico molecular. También se discute la importancia del diagnóstico molecular en relación con la composición y estructura de la población uruguaya.

Résumé L’association de l’allèle <FONT FACE=Symbol>b</FONT>S qui produit hémoglobine S (HbS) et d’un allèle de bêta tallasémie (<FONT FACE=Symbol>b</FONT>tal), arrive surtout chez des individus noirs d’Afrique et méditerranéens, et provoque un syndrome drépanocytaire appelé HbS-bêta tallasémie. Ce syndrome présente une grande hétérogé-néité clinique et génétique dûe surtout à l’allèle tallasémi-que présent. Les individus porteurs d’un allèle tallasémque <FONT FACE=Symbol>b</FONT>0 présentent en général,un cours clinique semblable aux homozygotes pour l’allèle <FONT FACE=Symbol>b</FONT>S de la HbS. En revanche, ceux qui portent un allèle <FONT FACE=Symbol>b</FONT>+ ont un cours clinique variable qui dépend de la réduction à la synthèse de la chaîne de beta globine. On décrit ici le cas de deux patients avec HbS-bêta tallasémie ayant consulté le Centre Hémato- Oncologique Pédiatrique de l’Hôpital Pereira Rossell. On analyse le génotype de deux patients au moyen de séquencement automatique du gène de bêta globine. On constate la présence de l’allèle tallasémique â+IVS-1-110G->A chez l’un des patients et de l’allèle <FONT FACE=Symbol>b</FONT>0 codon 39C->T chez l’autre. Les deux sont donc hétérozygotes composés <FONT FACE=Symbol>b</FONT>S/<FONT FACE=Symbol>b</FONT>tal. On discute ici le rapport entre les données cliniques et para cliniques et les résultats du diagnostic moléculaire.

Resumo A associação do alelo betaS que produz hemoglobina S (HbS) e de um alelo de beta talassemia betatal se dá principalmente em populações com ascendência africana e mediterrânea simultáneamente e provoca uma síndrome drepanocítica denominada HbS-beta talasemia. Esta síndrome apresenta uma grande heterogeneidade clínica e genética devida principalmente ao alelo para talassemia presente. Os indivíduos que são portadores de un alelo talassémico beta0 apresentam de maneira geral uma evolução clínica semelhante aos homozigotos para o alelo betaS da HbS. Por outro lado, os portadores do alelo beta+ apresentam um quadro clínico variável, dependendo da redução na síntese da cadeia beta-globina. Neste trabalho descrevemos os casos clínicos de dois pacientes com talassemia HbS.beta que foram admitidos no Centro Hemato-Oncológico Pediátrico do Hospital Pereira Rossel. O genotipo dos pacientes foi analizado pela sequenciação automática do gen da beta globina. A presença do alelo para talassemia beta+ IVS-1-110 G->A em um dos pacientes e do alelo beta0 codon39 C->T no outro foi demonstrada sendo os dois, por tanto, heterozi-gotos compostos betaS/betatal. Discute-se a relação entre os dados clínicos e paraclínicos com os resultados do diagnóstico molecular. Também se discute a importância do diagnóstico molecular em relação a composição e estrutura da população uruguaya.

Summary Association between allele betaS that produces hemoglobin S and allele (betatal) is mainly seen in African and Mediterranean populations, it causes the HbS-beta-thalassemia syndrome. This syndrome shows a wide range of clinical and genetic forms due mostly to the thalassemic allele. Carriers of thalassemic allele beta0 generally follow a similar clinical course to homocygote for talasémico betaS of the HbS. On the other hand, carriers of beta+ allele follow a variable clinical course, depending on the reduction of beta-globin chain. This study describe two clinical cases of patients with HbS-beta thalassemia of the Hematologic and Oncologic Centre of the Pereira Rossell Hospital. Genotypes of patients were analysed using automatic sequences of beta globin gen. Thalassemia allele beta+ IVS-1-110 G->A was seen in one patient and allele beta0 codon39 C->T in the other, so that both are compound heterozygous betaS/betatal. Clinical and paraclinical data is compared with molecular diagnostic findings; the importance of the molecular diagnosis in Uruguayan population is also discussed.