Mitochondrial DNA Variability among Six South American Amerindian Villages from the Pano Linguistic Group

Although scattered throughout a large geographic area, the members of the Pano linguistic group present strong ethnic, linguistic, and cultural homogeneity, a feature that causes them to be considered as components of a same “Pano” tribe. Nevertheless, the genetic homogeneity between Pano villages has not been examined. To study the genetic structure of the Pano linguistic group, four major Native American mitochondrial DNA (mtDNA) founder haplogroups were analyzed in 77 Amerindians from six villages of four Pano tribes (Katukina, Kaxináwa, Marúbo, and Yaminawa) located in the Brazilian Amazon. The central position of these tribes in the continent makes them relevant for attempts to reconstruct population movements in South America. Except for a single individual that presented an African haplogroup L, all remaining individuals presented one of the four Native American haplogroups. Significant heterogeneity was observed between the six Pano villages. Although Amerindian populations are usually characterized by considerable interpopulational diversity, the high heterogeneity level observed is unexpected if the strong ethnic, linguistic, and cultural homogeneity of the Pano linguistic group is taken into account. The present findings indicate that the ethnic, linguistic, and cultural homogeneity does not imply genetic homogeneity. Even though the genetic heterogeneity uncovered may be a female-specific process, the most probable explanation for that is the joint action of isolation and genetic drift as major factors influencing the genetic structure of the Pano linguistic group

Insights into HLA-G Genetics Provided by Worldwide Haplotype Diversity

Human leukocyte antigen G (HLA-G) belongs to the family of non-classical HLA class I genes, located within the major histocompatibility complex (MHC). HLA-G has been the target of most recent research regarding the function of class I non-classical genes. The main features that distinguish HLA-G from classical class I genes are (a) limited protein variability, (b) alternative splicing generating several membrane bound and soluble isoforms, (c) short cytoplasmic tail, (d) modulation of immune response (immune tolerance), and (e) restricted expression to certain tissues. In the present work, we describe the HLA-G gene structure and address the HLA-G variability and haplotype diversity among several populations around the world, considering each of its major segments [promoter, coding, and 3'untranslated region (UTR)] For this purpose, we developed a pipeline to reevaluate the 1000Genomes data and recover miscalled or missing genotypes and haplotypes. It became clear that the overall structure of the HLA-G molecule has been maintained during the evolutionary process and that most of the variation sites found in the HLA-G coding region are either coding synonymous or intronic mutations. In addition, only a few frequent and divergent extended haplotypes are found when the promoter, coding, and 3'UTRs are evaluated together. The divergence is particularly evident for the regulatory regions. The population comparisons confirmed that most of the HLA-G variability has originated before human dispersion from Africa and that the allele and haplotype frequencies have probably been shaped by strong selective pressures.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

The role of the placenta in the vertical transmission of HIV-1

A transmissão vertical (TV) consiste na principal forma de infecção pelo HIV-1 em menores de 13 anos e estimativas apontam que em 25% dos casos a transmissão tenha ocorrido intraútero. Nessas circunstâncias, o vírus de alguma forma ultrapassa a membrana placentária e chega ao sangue fetal. Esta revisão tem como objetivo realizar uma breve descrição sobre os mecanismos presentes na placenta humana que são capazes de gerar susceptibilidade ou proteção à TV do HIV-1. As células placentárias produzem um enorme grupo de citocinas, quimiocinas, hormônios e receptores que podem contribuir com o desfecho da transmissão do vírus ao concepto. Além disso, a capacidade do vírus de infectar as células placentárias também pode contribuir com a sua transmissão. Entretanto, o mecanismo pelo qual o vírus é capaz de sobrepujar a membrana placentária e as consequências dessa infecção no tecido placentário não estão totalmente elucidados. Dessa forma, novas pesquisas nessa área poderão contribuir com o desenvolvimento de estratégias profiláticas eficazes para redução da TV do HIV-1Vertical transmission (VT) is the main form of infection by HIV-1 in children under 13 years and estimates show that in 25% of cases intrauterine transmission has occurred. Under these circumstances, the virus somehow overcomes the placental membrane and reaches the fetal blood. This review aims to conduct a brief description of the mechanisms present in human placenta that are capable of generating susceptibility or resistance to VT of HIV-1. Placental cells produces a huge group of cytokines, chemokines, hormones and receptors that may contribute to the outcome of virus transmission to the fetus. Moreover, the ability of the virus to infect placental cells can also contribute to its transmission. However, the mechanism by which the virus is able to overcome the placental tissue is not fully elucidated. Thus, further research in this area may contribute to the development of effective preventive strategies to reduce the VT of HIV-

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good