Data analysis of 10 STR loci in a population in the province of Neuquen, Argentina

Abstract Ten Short Tandem Repeat (STR) loci, CSF1PO, TPOX, THO1, D12S1090, D3S1744, D18S849, FGA, D7S820, D1S533 and D9S304, were analyzed in a population geographically located at the foot of the Andes Range in the province of Neuquen, southwestern Argentina. Allele frequencies and paternity and forensic parameters (power of exclusion, matching probability, and power of discrimination) were calculated for all 10 STR loci. The population was analyzed for HardyWeinberg equilibrium (HWE) and allelic and gene frequencies were compared to those observed in the Buenos Aires population. Results indicate that the population was in HWE for these 10 STR loci. Significant differences between allele and genotype frequencies were found for the D7S820 locus (gene and genotypic differentiation test) when compared with data of the Buenos Aires population. These data indicate that the allele frequency estimations can be used to reliably calculate likelihood ratios for paternity and forensic DNA casework.

Genetic admixture patterns in argentinian patagonia

As in other Latin American populations, Argentinians are the result of the admixture amongst different continental groups, mainly from America and Europe, and to a lesser extent from Sub-Saharan Africa. However, it is known that the admixture processes did not occur homogeneously throughout the country. Therefore, considering the importance for anthropological, medical and forensic researches, this study aimed to investigate the population genetic structure of the Argentinian Patagonia, through the analysis of 46 ancestry informative markers, in 433 individuals from five different localities. Overall, in the Patagonian sample, the average individual ancestry was estimated as 35.8% Native American (95% CI: 32.2–39.4%), 62.1% European (58.5–65.7%) and 2.1% African (1.7–2.4%). Comparing the five localities studied, statistically significant differences were observed for the Native American and European contributions, but not for the African ancestry. The admixture results combined with the genealogical information revealed intra-regional variations that are consistent with the different geographic origin of the participants and their ancestors. As expected, a high European ancestry was observed for donors with four grandparents born in Europe (96.8%) or in the Central region of Argentina (85%). In contrast, the Native American ancestry increased when the four grandparents were born in the North (71%) or in the South (61.9%) regions of the country, or even in Chile (60.5%). In summary, our results showed that differences on continental ancestry contribution have different origins in each region in Patagonia, and even in each locality, highlighting the importance of knowing the origin of the participants and their ancestors for the correct interpretation and contextualization of the genetic information.Finantial support was granted by Agencia Nacional de Promoción Científica y Tecnológica, Argentina (ANPCyT; https://www.argentina.gob.ar/ ciencia/agencia; grants ref. MPL PICT 2013-2414, JLL PICT 2014-1558), and Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq; http://www.cnpq.br; grant ref. LG 305330/2016-0)

Analysis of paternal lineages in Brazilian and African populations

The present-day Brazilian population is a consequence of the admixture of various peoples of very different origins, namely, Amerindians, Europeans and Africans. The proportion of each genetic contribution is known to be very heterogeneous throughout the country. The aim of the present study was to compare the male lineages present in two distinct Brazilian populations, as well as to evaluate the African contribution to their male genetic substrate. Thus, two Brazilian population samples from Manaus (State of Amazon) and Ribeirão Preto (State of São Paulo) and three African samples from Guinea Bissau, Angola and Mozambique were typed for a set of nine Y chromosome specific STRs. The data were compared with those from African, Amerindian and European populations. By using Y-STR haplotype information, low genetic distances were found between the Manaus and Ribeirão Preto populations, as well as between these and others from Iberia. Likewise, no significant distances were observed between any of the African samples from Angola, Mozambique and Guinea Bissau. Highly significant Rst values were found between both Brazilian samples and all the African and Amerindian populations. The absence of a significant Sub-Saharan African male component resulting from the slave trade, and the low frequency in Amerindian ancestry Y-lineages in the Manaus and Ribeirão Preto population samples are in accordance with the accentuated gender asymmetry in admixture processes that has been systematically reported in colonial South American populations

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

Analysis of paternity index of 164 paternity trios DNA-typed by either 10 STR or 4 RFLP loci

Abstract In the past few years, short tandem repeat (STR) typing has become the method of choice for many, if not most, laboratories to perform paternity testing. The aim of this study was to show that a set of carefully chosen and well-known STR loci may provide as reliable results as Restriction Fragment Length Polymorphism (RFLP) typing does. We analyzed the Paternity Index (PI) and Residual Paternity Index (RPI) obtained in 67 non-exclusion cases and 22 exclusion cases typed by 10 STR loci, and in 61 non-exclusions and 14 exclusions typed by four RFLP loci. PI was calculated for the trios and also for child and alleged father in motherless cases using local frequency tables and it was assigned to one out of six categories. The 10 STR locus analysis for paternity testing led to conclusive results for all trio cases. In paternity tests lacking a mother, more than 10 STRs should be analyzed to get similar results.

Genetic Testing of Familial Hypercholesterolemia in a Hospital-Based Population of the City of Buenos Aires

Background: Familial hypercholesterolemia is a primary hyperlipidemia. It is an autosomal dominant genetic disorder of lipoprotein metabolism, characterized by elevated plasma low-density lipoprotein cholesterol and presence of tendon xanthomas, and is associated with early cardiovascular disease. Objectives: The aim of this study was to investigate the presence of mutations in the main gene associated with the development of familial hypercholesterolemia (LDLR) in a group of patients identified as “index cases” attending the Lipid Clinic of the Hospital Universitario Fundación Favaloro with clinical diagnosis of familial hypercholesterolemia. The ancestral composition of the study population was determined. Methods: We evaluated 38 patients with clinical diagnosis of familial hypercholesterolemia. Mutation screening of the LDLR gene coding regions and adjacent intronic areas was performed using Sanger sequencing. The ancestral component of the study population was investigated using 46 ancestry inference markers (AIM-Indel). Results: Fifty different variants were identified, 48% of which were considered pathogenic. A genotype-phenotype severity correlation was established in 60.5% of the patients evaluated. The ancestral component of the study population was predominantly European, followed by native-American and African in lower proportion. Conclusions: Genetic testing by LDLR gene sequencing in patients identified as “index cases” with clinical diagnosis of familial hypercholesterolemia allows the correlation between the genetic information and the severity of the clinical phenotype to a cascade testing of the family members presenting the inclusion criteria considered.Introducción: La hipercolesterolemia familiar es una hiperlipidemia primaria. Se trata de un trastorno genético autosómico dominante del metabolismo de las lipoproteínas, caracterizado por concentraciones plasmáticas elevadas de colesterol unido a lipoproteínas de baja densidad y presencia de xantomas tendinosos, y está asociado con el desarrollo prematuro de enfermedad cardiovascular. Objetivos: Investigar la presencia de mutaciones en el principal gen asociado al desarrollo de hipercolesterolemia familiar (LDLR) en un grupo de pacientes identificados como “casos índices”, de entre aquellos que concurren al Servicio de Lípidos del Hospital Universitario Fundación Favaloro con diagnóstico clínico de hipercolesterolemia familiar. Determinar la composición ancestral de la población estudiada. Material y métodos: Se estudió una población de 38 pacientes con diagnóstico clínico de hipercolesterolemia familiar. La región codificante y las zonas intrónicas adyacentes del gen LDLR se secuenciaron automáticamente por el método de Sanger. Se investigó el componente ancestral de la población estudiada a partir del análisis de 46 marcadores informativos de ancestralidad (AIM-Indel). Resultados: Se identificaron 50 variantes diferentes, de las cuales el 48% se consideraron patogénicas. Se logró establecer una correlación genotipo-gravedad del fenotipo en el 60,5% de los pacientes estudiados. El componente ancestral de la población estudiada fue predominantemente europeo, seguido de un componente nativo-americano y, en menor proporción, africano. Conclusiones: El análisis genético por secuenciación del gen LDLR en pacientes identificados como “casos índices” con diagnóstico clínico de hipercolesterolemia familiar permite correlacionar el dato genético con la gravedad del fenotipo observado clínicamente y efectuar un diagnóstico en cascada en los miembros de la familia que presentan los criterios de inclusión considerados

Immunological status of isolated lymphoid follicles after intestinal transplantation

Intestinal transplantation (ITx) faces the challenge of grafting a high immunogenic organ, which is certainly one of the major obstacles for intestinal allograft acceptance. The allograft has to guarantee the proper functioning of the mucosal immune machinery under immunosuppressive conditions. Recently, it has been elucidated that isolated lymphoid follicles (ILFs) are an indispensable part of mucosal immunity to maintain IgA synthesis and consequently to control commensal microflora. No data about these follicular structures in the setting of ITx are available so far. Therefore, we addressed the question whether constitution, integrity and function of allograft ILFs are disturbed by immunosuppressive regimen. We compared allograft ILFs from terminal ileum of transplant patients with ILFs from nontransplant patients via flow cytometry, quantitative real-time polymerase chain reaction and immunohistochemistry. We found that host leukocytes rapidly repopulate allograft ILFs and that maintenance immunosuppressive regimen, tacrolimus and corticosteroids, does not affect their cellular integrity and function. However, allograft ILFs revealed a higher maturation state than control samples and IgA positive plasma cells were increased in number in allograft mucosa. Our results open the path for a better understanding of allograft mucosal immunity. This study shows that cellular integrity and function of isolated lymphoid follicles in the small bowel of transplanted patients are not affected by the immunosuppressive regimen, and that these lymphoid structures serve to better understand the mucosal immunity of the intestinal allograft.Fil: Meier, Dominik. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; ArgentinaFil: Ramisch, D.. Fundación Favaloro; ArgentinaFil: Toscanini, U.. Fundación Favaloro; ArgentinaFil: Berardi, G.. Fundación Favaloro; ArgentinaFil: Gondolesi, Gabriel Eduardo. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rumbo, Martín. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin