Interethnic admixture and the evolution of Latin American populations

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

Invisibilidad Indígena en el Uruguay: Genética, Historia y Género

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", which culminated in the 2011 Census. In this, 2.5% of the population recognized indigenous ancestry as their main ancestry, and 5.1% declared that they had indigenous ancestors. These data are not consistent with those observed when studying maternal or autosomal genetic ancestry (35 and 14% native contribution, respectively.The facts and processes that led to the invisibility of native people and their descendants are analyzed from historical sources, and in particular, their geographical distribution and socioeconomic level. It is also analyzed the gender of those who were integrated into the national society, and the lack of voice of women over a long period, since it was indigenous women that were integrated into the national society.  La población uruguaya ha sido tradicionalmente considerada como "sin indios". Luego de casi 150 años, en 1996 se comenzó a interrogar a la población sobre "etnia o raza", lo cual culminó en el Censo de 2011. En este, 2,5% de la población reconoció como ancestría principal la indígena, y 5,1% declaró tener ancestros indígenas. Estos datos no son coherentes con los observados al estudiar ancestría genética materna o autosómica (35 y 14% de aporte indígena, respectivamente). Se analizan los hechos y procesos que condujeron a la invisibilización de los indígenas y sus descendientes a partir de fuentes históricas, y en particular, en su distribución geográfica y nivel socioeconómico. Se analiza también el género de quienes pasaron a formar pate de la sociedad nacional, y la falta de voz de las mujeres durante un largo período, puesto que fueron mujeres indígenas quienes mayoritariamente se intergraron a la sociedad nacional.A população uruguaia é tradicionalmente considerada "sem índios". Passados ​​quase 150 anos, em 1996 a população passou a ser questionada sobre "etnia ou raça", o que culminou no Censo 2011. Neste, 2,5% da população reconheceu o indígena como sua ancestralidade principal, e 5,1% declarou ter ancestrais indígenas. Esses dados não são consistentes com os observados ao estudar a ancestralidade genética materna ou autossômica (35 e 14% de contribuição indígena, respectivamente). Os fatos e processos que levaram à invisibilidade dos povos indígenas e seus descendentes são analisados ​​a partir de fontes históricas e, em particular, sua distribuição geográfica e nível socioeconômico. Também e investigado o gênero daqueles que se tornaram parte da sociedade nacional, e a falta de voz das mulheres por um longo período visto que foram as mulheres indígenas quem principalmente formam integradass à sociedade nacional

The last Charrua Indian; (Uruguay): analysis of the remains of Chief Vaimaca Perú.

Uruguay is the only Latin American country that at present lacks Native populations and little is known about its prehistoric populations. In the construction of National identity, the unique reference to Natives is about Charra Indians, one of the most important ethnic groups that lived in the territory and exterminated in the 1830s. In 1833, four survivors were taken to be exhibited and studied in France, becoming martyrs and a symbol of their nation. The skeletal remains of Chief Perú were preserved and studied mainly by Rivet1; these are the only remains certainly identified as belonging to a Charrúa. In 2002, the French government returned the remains to Uruguay, where they were buried with honours at the National Pantheon. Before the burial, we performed morphological studies as well as extracted samples for DNA analysis. Peru's morphology is coherent with the one of a nomadic warrior: robust body with strong muscular insertions, wounds, and healthy diet based mainly on meat. Here we show that metric and morphological data as well as maternal inherited mitochondrial DNA (mtDNA) hypervariable region I (HVRI) and restriction fragment length polymorphisms (RFLPs), indicate a close relationship with Pampa-Patagonian Indians, and specially, with prehistoric Natives buried in mounds from eastern Uruguay. This last finding is particularly important to understand Uruguayan prehistory and history, raising the debate about who the mound builders were, and showing continuity between them, historic Charrúa Indians, and present populations

Cardiovascular risk estimated after 13 years of follow-up in a low-incidence Mediterranean region with high-prevalence of cardiovascular risk factors

<p>Abstract</p> <p>Background</p> <p>Murcia (south-east Spain) shows increased cardiovascular (CV) morbimortality as compared to other Spanish regions. Our objective was to assess the CV risk associated with major risk factors (RF) among adult population of Murcia.</p> <p>Methods</p> <p>A cohort of 2314 subjects (18-70 years) with full biochemical and questionnaire data was followed-up for 13 years. Incident cases of ischemic heart disease and stroke were identified by record linkage, individual questionnaires and revision of medical records. Relative risks were obtained by multivariate Cox regression stratified by age and sex, and ischemic risk attributable to CVRF was calculated.</p> <p>Results</p> <p>After more than 26276 person-years of follow-up, 57 incident ischemic events (77% men) and 37 stroke cases (62% men) were identified. Independent risk factors of ischemic heart disease (IHD) and all CV events combined, with RR ranging from 1.6 to 2.6, were total serum cholesterol ≥ 240 mg/dl (HR = 2.6, 95%CI:1.3-5.1), blood pressure levels ≥ 140/90 mmHg (HR = 2.6, 95%CI:1.4-4.8), ever tobacco smoking (HR = 2.2; 95%CI:1.1-4.5), and diabetes (HR = 2.0; 95%CI: 1.0-3.8). No increased CV risk was detected for known participants under treatment who showed cholesterol and blood pressure values below the clinical risk threshold. Smoking was significantly associated with stroke. For all events combined, the major risk factors were hypercholesterolemia, hypertension and ever use of tobacco. Despite its high prevalence, obesity was not associated to CV risk. Most of the IHD cases were attributable to smoking (44%), hypertension (38%) and hypercholesterolemia (26%).</p> <p>Conclusions</p> <p>In the Region of Murcia, smoking accounted for the largest proportion of cardiovascular risk, whereas hypertension displaced hypercholesterolemia as the second leading cause of CV disease. Our study deepens in our understanding of the cardiovascular epidemiology in Spanish areas of Mediterranean Europe with relatively high cardiovascular morbimortality, that are poorly represented by the available risk equations.</p

Recomendaciones de manejo de la afectación renal en el complejo esclerosis tuberosa

El complejo esclerosis tuberosa (CET) es una enfermedad rara, hereditaria, multisistémica y con un amplio espectro fenotípico. Su manejo requiere de la colaboración de múltiples especialistas. Así como en la edad pediátrica cobra un especial relieve el neurólogo pediatra, en la edad adulta la afectación renal es la causante de la mayor morbimortalidad. Existen diversas recomendaciones sobre el manejo general del paciente con CET, pero ninguna que se centre en la afectación renal. Las presentes recomendaciones responden a la necesidad de proporcionar pautas para facilitar un mejor conocimiento y manejo diagnóstico-terapéutico de la afectación renal del CET mediante un uso racional de las pruebas complementarias y el empleo correcto de los tratamientos disponibles. Su elaboración se ha basado en el consenso dentro del grupo de trabajo de enfermedades renales hereditarias de la SEN/REDINREN. Ha contado con la participación de especialistas en CET no nefrólogos también con el fin de ampliar la visión de la enfermedad

Autosomal dominant polycystic kidney disease in young adults

Background The clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD) usually appear in adulthood, however pediatric series report a high morbidity. The objective of the study was to analyze the clinical characteristics of ADPKD in young adults. Methods Family history, hypertension, albuminuria, estimated glomerular filtration rate (eGFR) and imaging tests were examined in 346 young adults (18-30 years old) out of 2521 patients in the Spanish ADPKD registry (REPQRAD). A literature review searched for reports on hypertension in series with more than 50 young (age <30 years) ADPKD patients. Results The mean age of this young adult cohort was 25.24 (SD 3.72) years. The mean age at diagnosis of hypertension was 21.15 (SD 4.62) years, while in the overall REPQRAD population was aged 37.6 years. The prevalence of hypertension was 28.03% and increased with age (18-24 years, 16.8%; 25-30 years, 36.8%). Although prevalence was lower in women than in men, the age at onset of hypertension (21 years) was similar in both sexes. Mean eGFR was 108 (SD 21) mL/min/1.73 m(2), 38.0% had liver cysts and 3.45% of those studied had intracranial aneurysms. In multivariate analyses, hematuria episodes and kidney length were independent predictors of hypertension (area under the curve 0.75). The prevalence of hypertension in 22 pediatric cohorts was 20%-40%, but no literature reports on hypertension in young ADPKD adults were found. Conclusions Young adults present non-negligible ADPKD-related morbidity. This supports the need for a thorough assessment of young adults at risk of ADPKD that allows early diagnosis and treatment of hypertension. Lay Summary Impairment of renal function usually develops from the fourth decade of life in autosomal dominant polycystic kidney disease (ADPKD). However, hypertension precedes the onset of renal insufficiency. In published pediatric series, the prevalence of hypertension is 20%-40%. However, clinical information on young adults with ADPKD is scarce. We present the largest cohort of young adults (age 18-30 years) with ADPKD published to date. Prevalence of hypertension is 28% and increases with age, reaching 36.8% in the subgroup aged 25-30 years, despite normal glomerular filtration rate and albuminuria. The prevalence of hypertension is higher in males, but the mean age at diagnosis (21 years) was similar in both sexes. Young adults present non-negligible ADPKD-related morbidity. This supports the need for a thorough assessment that allows early diagnosis and treatment of hypertension, before decline of estimated glomerular filtration rate. Ambulatory blood pressure monitoring may be especially useful in this regard.11 página

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Magnetic Hydroxyapatite Bone Substitutes to Enhance Tissue Regeneration: Evaluation In Vitro Using Osteoblast-Like Cells and In Vivo in a Bone Defect

In case of degenerative disease or lesion, bone tissue replacement and regeneration is an important clinical goal. In particular, nowadays, critical size defects rely on the engineering of scaffolds that are 3D structural supports, allowing cellular infiltration and subsequent integration with the native tissue. Several ceramic hydroxyapatite (HA) scaffolds with high porosity and good osteointegration have been developed in the past few decades but they have not solved completely the problems related to bone defects. In the present study we have developed a novel porous ceramic composite made of HA that incorporates magnetite at three different ratios: HA/Mgn 95/5, HA/Mgn 90/10 and HA/Mgn 50/50. The scaffolds, consolidated by sintering at high temperature in a controlled atmosphere, have been analysed in vitro using human osteoblast-like cells. Results indicate high biocompatibility, similar to a commercially available HA bone graft, with no negative effects arising from the presence of magnetite or by the use of a static magnetic field. HA/Mgn 90/10 was shown to enhance cell proliferation at the early stage. Moreover, it has been implanted in vivo in a critical size lesion of the rabbit condyle and a good level of histocompatibility was observed. Such results identify this scaffold as particularly relevant for bone tissue regeneration and open new perspectives for the application of a magnetic field in a clinical setting of bone replacement, either for magnetic scaffold fixation or magnetic drug delivery

No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

We evaluated the genetic contribution of the T cell-erestricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated