TagSNP transferability and relative loss of variability prediction from HapMap to an admixed population

<p>Abstract</p> <p>Background</p> <p>The application of a subset of single nucleotide polymorphisms, the tagSNPs, can be useful in capturing untyped SNPs information in a genomic region. TagSNP transferability from the HapMap dataset to admixed populations is of uncertain value due population structure, admixture, drift and recombination effects. In this work an empirical dataset from a Brazilian admixed sample was evaluated against the HapMap population to measure tagSNP transferability and the relative loss of variability prediction.</p> <p>Methods</p> <p>The transferability study was carried out using SNPs dispersed over four genomic regions: the PTPN22, HMGCR, VDR and CETP genes. Variability coverage and the prediction accuracy for tagSNPs in the selected genomic regions of HapMap phase II were computed using a prediction accuracy algorithm. Transferability of tagSNPs and relative loss of prediction were evaluated according to the difference between the Brazilian sample and the pooled and single HapMap population estimates.</p> <p>Results</p> <p>Each population presented different levels of prediction per gene. On average, the Brazilian (BRA) sample displayed a lower power of prediction when compared to HapMap and the pooled sample. There was a relative loss of prediction for BRA when using single HapMap populations, but a pooled HapMap dataset generated minor loss of variability prediction and lower standard deviations, except at the VDR locus at which loss was minor using CEU tagSNPs.</p> <p>Conclusion</p> <p>Studies that involve tagSNP selection for an admixed population should not be generally correlated with any specific HapMap population and can be better represented with a pooled dataset in most cases.</p

Effects of acute aerobic exercise on rats serum extracellular vesicles diameter, concentration and small RNAs content

Physical exercise stimulates organs, mainly the skeletal muscle, to release a broad range of molecules, recently dubbed exerkines. Among them, RNAs, such as miRNAs, piRNAs, and tRNAs loaded in extracellular vesicles (EVs) have the potential to play a significant role in the way muscle and other organs communicate to translate exercise into health. Low, moderate and high intensity treadmill protocols were applied to rat groups, aiming to investigate the impact of exercise on serum EVs and their associated small RNA molecules. Transmission electron microscopy, resistive pulse sensing, and western blotting were used to investigate EVs morphology, size distribution, concentration and EVs marker proteins. Small RNA libraries from EVs RNA were sequenced. Exercise did not change EVs size, while increased EVs concentration. Twelve miRNAs were found differentially expressed after exercise: rno-miR-128-3p, 1033p, 330-5p, 148a-3p, 191a-5p, 10b-5p, 93-5p, 25-3p, 142-5p, 3068-3p, 142-3p, and 410-3p. No piRNA was found differentially expressed, and one tRNA, trna8336, was found down-regulated after exercise. The differentially expressed miRNAs were predicted to target genes involved in the MAPK pathway. A single bout of exercise impacts EVs and their small RNA load, reinforcing the need for a more detailed investigation into EVs and their load as mediators of health-promoting exercise

Polymorphism analysis of the CTLA-4 gene in paracoccidioidomycosis patients

The CTLA-4 protein is expressed in activated T cells and plays an essential role in the immune response through its regulatory effect on T cell activation. Polymorphisms of the CTLA-4 gene have been correlated with autoimmune, neoplastic and infectious illnesses. This work aimed to verify possible associations between single nucleotide polymorphisms (SNPs) in CTLA-4, -318C/T in the promoter and +49A/G in exon 1 and paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis. For this purpose, 66 chronic form PCM patients and 76 healthy controls had their allele, genotype and haplotype frequencies determined. The genetic admixture structure of the patients and controls was evaluated to eliminate ancestral bias. The comparison of frequencies indicated no significant differences between patients and controls that could link the SNPs to PCM. Groups were admixture matched with no difference observed in population ancestry inference, indicating that the absence of association between CTLA-4 polymorphisms and PCM could not be attributed to ancestral bias. This study showed that there was no association between the CTLA-4 SNPs -318 and +49 and the resistance or susceptibility to PCM.22022

Estudo comparativo da função do assoalho pélvico em mulheres continentes e incontinentes na pós menopausa

CONTEXTUALIZAÇÃO: A incontinência urinária (IU) é de causa multifatorial, sendo atribuída, em parte, à fraqueza da musculatura do assoalho pélvico. Apesar de ser subestimada por muitas mulheres, a avaliação funcional do assoalho pélvico (AFA) pode contribuir para um correto diagnóstico e terapêutica adequada. OBJETIVOS: Comparar a função muscular do assoalho pélvico em mulheres continentes e incontinentes na pós menopausa como fator diagnóstico no tratamento da IU. MÉTODOS: A partir da investigação dos sintomas urinários, 153 mulheres (idade X=66,7±5,4) foram separadas em dois grupos (G1 incontinentes e G2 assintomáticas). Após análise dos critérios de inclusão, as mulheres foram submetidas à AFA por meio da palpação bidigital (classificação de Contreras Ortis, 1994) e à quantificação da pressão de contração perineal por meio do perineômetro (PERINA 996-2® QUARK). RESULTADOS: Observou-se prevalência de IU (54,9%) na amostra estudada, sendo a incontinência urinária de esforço (IUE) (41,7%) o tipo mais presente. Em relação aos sintomas urinários, como a frequência miccional diurna (p=0,004) e noturna (p=0,02), o grupo G1 apresentou um valor significativamente mais alto. A AFA mostrou resultados similares durante a palpação e o perineômetro, com diferenças significativas (p<0,001) entre os dois grupos. Utilizou-se estatística descritiva, teste t de Student para amostras independentes, medidas de prevalência e análise de variância (one-way ANOVA), seguida do post hoc de Bonferroni (p<0,05). O software Statistical Package for the Social Sciences (SPSS) versão 10,0 (SPSS, Chicago, IL) foi utilizado para realização de todas as análises. CONCLUSÕES: A palpação e o perineômetro se mostraram eficientes na avaliação da força e pressão de contração desse grupo muscular.BACKGROUND: Urinary incontinence (UI) is multifactorial and attributed, in part, to weakness of the pelvic floor muscles. Despite being underestimated by many women, a functional pelvic floor assessment (FPA) may contribute to a correct diagnosis and appropriate treatment. OBJECTIVES: To compare the function of pelvic floor muscles in continent and incontinent postmenopausal women as a diagnostic factor in UI treatment. METHODS: Based on the investigation of urinary symptoms, 153 women (age X=66.7±5.4) were divided into two groups (G1-incontinent and G2-continent). After analysis of the inclusion criteria, the women were submitted to FPA by means of bidigital palpation according to Contreras Ortiz (1994) and quantification of perineal strength with a perineometer (PERINA 996-2 QUARK®). RESULTS: There was prevalence of UI (54.9%) in the sample, with stress urinary incontinence (41.7%) as the most common. Regarding urinary symptoms such as diurnal (p=0.004) and nocturnal (p=0.02) voiding frequency, G1 had a significantly higher value. The FPA found similar results via palpation and the perineometer, with significant differences (p<0.001) between the two groups. We used descriptive statistics, the Student t test for independent samples, measures of prevalence and one-way ANOVA, followed by Bonferroni's post-hoc test (p<0.05). The software Statistical Package for the Social Sciences (SPSS) version 10.0 (SPSS, Chicago, IL) was used to perform all tests. CONCLUSIONS: Palpation and the perineometer were efficient forms of assessing the force and pressure of the muscle contractions of this muscle group

A linkage map for the B-genome of Arachis (Fabaceae) and its synteny to the A-genome

<p>Abstract</p> <p>Background</p> <p><it>Arachis hypogaea </it>(peanut) is an important crop worldwide, being mostly used for edible oil production, direct consumption and animal feed. Cultivated peanut is an allotetraploid species with two different genome components, A and B. Genetic linkage maps can greatly assist molecular breeding and genomic studies. However, the development of linkage maps for <it>A. hypogaea </it>is difficult because it has very low levels of polymorphism. This can be overcome by the utilization of wild species of <it>Arachis</it>, which present the A- and B-genomes in the diploid state, and show high levels of genetic variability.</p> <p>Results</p> <p>In this work, we constructed a B-genome linkage map, which will complement the previously published map for the A-genome of <it>Arachis</it>, and produced an entire framework for the tetraploid genome. This map is based on an F₂population of 93 individuals obtained from the cross between the diploid <it>A. ipaënsis </it>(K30076) and the closely related <it>A. magna </it>(K30097), the former species being the most probable B genome donor to cultivated peanut. In spite of being classified as different species, the parents showed high crossability and relatively low polymorphism (22.3%), compared to other interspecific crosses. The map has 10 linkage groups, with 149 loci spanning a total map distance of 1,294 cM. The microsatellite markers utilized, developed for other <it>Arachis </it>species, showed high transferability (81.7%). Segregation distortion was 21.5%. This B-genome map was compared to the A-genome map using 51 common markers, revealing a high degree of synteny between both genomes.</p> <p>Conclusion</p> <p>The development of genetic maps for <it>Arachis </it>diploid wild species with A- and B-genomes effectively provides a genetic map for the tetraploid cultivated peanut in two separate diploid components and is a significant advance towards the construction of a transferable reference map for <it>Arachis</it>. Additionally, we were able to identify affinities of some <it>Arachis </it>linkage groups with <it>Medicago truncatula</it>, which will allow the transfer of information from the nearly-complete genome sequences of this model legume to the peanut crop.</p

Identification of candidate genome regions controlling disease resistance in Arachis

<p>Abstract</p> <p>Background</p> <p>Worldwide, diseases are important reducers of peanut (<it>Arachis hypogaea</it>) yield. Sources of resistance against many diseases are available in cultivated peanut genotypes, although often not in farmer preferred varieties. Wild species generally harbor greater levels of resistance and even apparent immunity, although the linkage of agronomically un-adapted wild alleles with wild disease resistance genes is inevitable. Marker-assisted selection has the potential to facilitate the combination of both cultivated and wild resistance loci with agronomically adapted alleles. However, in peanut there is an almost complete lack of knowledge of the regions of the <it>Arachis </it>genome that control disease resistance.</p> <p>Results</p> <p>In this work we identified candidate genome regions that control disease resistance. For this we placed candidate disease resistance genes and QTLs against late leaf spot disease on the genetic map of the A-genome of <it>Arachis</it>, which is based on microsatellite markers and legume anchor markers. These marker types are transferable within the genus <it>Arachis </it>and to other legumes respectively, enabling this map to be aligned to other <it>Arachis </it>maps and to maps of other legume crops including those with sequenced genomes. In total, 34 sequence-confirmed candidate disease resistance genes and five QTLs were mapped.</p> <p>Conclusion</p> <p>Candidate genes and QTLs were distributed on all linkage groups except for the smallest, but the distribution was not even. Groupings of candidate genes and QTLs for late leaf spot resistance were apparent on the upper region of linkage group 4 and the lower region of linkage group 2, indicating that these regions are likely to control disease resistance.</p

Effects of endurance racing on horse plasma extracellular particle miRNA

Background: Physical exercise is an essential factor in preventing and treating metabolic diseases by promoting systemic benefits throughout the body. The molecular factors involved in this process are poorly understood. Micro RNAs (miRNAs) are small non-coding RNAs that inhibit mRNA transcription. MiRNAs, which can participate in the benefits of exercise to health, circulate in plasma in extracellular particles (EP). Horses that undergo endurance racing are an excellent model to study the impact of long-duration/low intensity exercise in plasma EP miRNAs. Objectives: To evaluate the effects of 160 km endurance racing on horse plasma extracellular particles and their miRNA population. Study design: Cohort study. Methods: We collected plasma from five Arabian horses during five time-points of an endurance ride. Extracellular particles were purified from plasma and characterised by electron microscopy, resistive pulse sensing (qNano) and western blotting. Small RNAs were purified from horse plasma EP, and sequencing was performed. Results: Endurance racing increased EP concentration and average diameter compared to before the race. Western blotting showed a high concentration of extracellular vesicles proteins 2 hours after the race, which returned to baseline 15 hours after the race. MicroRNA differential expression analysis revealed increasing levels of eca-miR-486-5p during and after the race, and decreasing levels of eca-miR-9083 after the end. Conclusions: This study adds new data about the variation in plasma EP concentrations after long-distance exercise and brings new insights about the roles of exercise-derived EP miRNAs during low-intensity endurance exercise

A Worldwide Phylogeography for the Human X Chromosome

BACKGROUND: We reasoned that by identifying genetic markers on human X chromosome regions where recombination is rare or absent, we should be able to construct X chromosome genealogies analogous to those based on Y chromosome and mitochondrial DNA polymorphisms, with the advantage of providing information about both male and female components of the population. METHODOLOGY/PRINCIPAL FINDINGS: We identified a 47 Kb interval containing an Alu insertion polymorphism (DXS225) and four microsatellites in complete linkage disequilibrium in a low recombination rate region of the long arm of the human X chromosome. This haplotype block was studied in 667 males from the HGDP-CEPH Human Genome Diversity Panel. The haplotypic diversity was highest in Africa (0.992+/-0.0025) and lowest in the Americas (0.839+/-0.0378), where no insertion alleles of DXS225 were observed. Africa shared few haplotypes with other geographical areas, while those exhibited significant sharing among themselves. Median joining networks revealed that the African haplotypes were numerous, occupied the periphery of the graph and had low frequency, whereas those from the other continents were few, central and had high frequency. Altogether, our data support a single origin of modern man in Africa and migration to occupy the other continents by serial founder effects. Coalescent analysis permitted estimation of the time of the most recent common ancestor as 182,000 years (56,700-479,000) and the estimated time of the DXS225 Alu insertion of 94,400 years (24,300-310,000). These dates are fully compatible with the current widely accepted scenario of the origin of modern mankind in Africa within the last 195,000 years and migration out-of-Africa circa 55,000-65,000 years ago. CONCLUSIONS/SIGNIFICANCE: A haplotypic block combining an Alu insertion polymorphism and four microsatellite markers on the human X chromosome is a useful marker to evaluate genetic diversity of human populations and provides a highly informative tool for evolutionary studies