Assessing Individual Interethnic Admixture and Population Substructure Using a 48-Insertion-Deletion (INSEL) Ancestry-Informative Marker (AIM) Panel

Estimating the proportions of different ancestries in admixed populations is very important in population genetics studies, and it is particularly important for detecting population substructure effects in case-control association studies. In this work, a set of 48 ancestry, informative insertion, deletion polymorphisms (INDELs) were selected with the goal of efficiently measuring the proportions of three different ancestries (sub-Saharan African, European, and Native American) in mixed populations. All selected markers can be easily analyzed via multiplex PCR and detected with standard capillary electrophoresis. A total of 593 unrelated individuals representative of European, African, and Native American parental populations were typed, as were 380 individuals from three Brazilian populations with known admixture patterns. As expected, the interethnic admixture estimates show that individuals from southern Brazil present an almost exclusively European ancestry; Afro-descendant communities in the Amazon region, apart from the major African contribution, present some degree of admixture with Europeans and Native Americans; and a sample from Belem, in the northeastern Amazon, shows a significant contribution of the three ethnic groups, although with a greater European proportion. In summary, a panel of ancestry-informative INDELs was optimized and proven to be a variable tool for estimating individual and global ancestry proportions in admixed populations. The ability to accurately infer interethnic admixtures highlights the usefulness of this marker set for assessing population substructure in association studies, particularly those conducted in Brazilian and other Latin American populations sharing trihybrid ancestry patterns. Hum Mutat 31:184-190, 2010. (C) 2009 Wiley-Liss, Inc.

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein-protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation.

Global poly(A) mRNA expression profile measured in individual bovine oocytes and cleavage embryos

The objective of this article was to estimate quantitative differences for GAPDH transcripts and poly(A) mRNA: (i) between oocytes collected from cumulus-oocyte complexes (COCs) qualified morphologically as grades A and B; (ii) between grade A oocytes before and after in vitro maturation (IVM); and (iii) among in vitro-produced embryos at different developmental stages. To achieve this objective a new approach was developed to estimate differences between poly(A) mRNA when using small samples. The approach consisted of full-length cDNA amplification (acDNA) monitored by real-time PCR, in which the cDNA from half of an oocyte or embryo was used as a template. The GAPDH gene was amplified as a reverse transcription control and samples that were not positive for GAPDH transcripts were discarded. The fold differences between two samples were estimated using delta Ct and statistical analysis and were obtained using the pairwise fixed reallocation randomization test. It was found that the oocytes recovered from grade B COCs had quantitatively less poly(A) mRNA (p < 0.01) transcripts compared with grade A COCs (1 arbitrary unit expression rate). In the comparison with immature oocytes (I arbitrary unit expression rate), the quantity of poly(A) mRNA did not change during IVM, but declined following IVF and varied with embryo culture (p < 0.05). Amplification of cDNA by real-time PCR was an efficient method to estimate differences in the amount of poly(A) mRNA between oocytes and embryos. The results obtained from individual oocytes suggested an association between poly(A) mRNA abundance and different morphological qualities of oocytes from COCs. In addition, a poly(A) mRNA profile was characterized from oocytes undergoing IVM, fertilization and blastocyst heating.

Determination of temperature variation during the individual steps of the production of hospital diets of modified consistency

Background & aim: Many disease outbreaks of food origin are caused by foods prepared in Food Service and Nutrition Units of hospitals, affecting hospitalized patients who, in most cases, are immunocompromised and therefore at a higher risk of severe worsening of their clinical status. The aim of this study was to determine the variations in temperature and the time-temperature factor of hospital diets. Methods: The time and temperature for the preparation of 4 diets of modified consistency were determined on 5 nonconsecutive days in a hospital Diet and Nutrition Unit at the end of preparation and during the maintenance period, portioning and distribution at 3 sites, i.e., the first, the middle and the last to receive the diets. Results and discussion: All foods reached an adequate temperature at the end of cooking, but temperature varied significantly from the maintenance period to the final distribution, characterizing critical periods for microorganism proliferation. During holding, temperatures that presented a risk were reached by 16.7% of the meats and 59% of the salads of the general diet, by 16.7% of the garnishes in the bland diet and by 20% of the meats and garnishes in the viscous diet. The same occurred at the end of distribution for 100% of the hot samples and of the salads and for 61% of the desserts. None of the preparations remained at risk temperature for a time exceeding that established by law. Conclusion: The exposure to inadequate temperature did not last long enough to pose risks to the patient.

Mineralocorticoid Receptor Mutations Differentially Affect Individual Gene Expression Profiles in Pseudohypoaldosteronism Type 1

Context: Type 1 pseudohypoaldosteronism (PHA1), a primary form of mineralocorticoid resistance, isdueto inactivating mutations of the NR3C2 gene, coding for the mineralocorticoid receptor (MR). Objective: The objective of the study was to assess whether different NR3C2 mutations have distinct effects on the pattern of MR-dependent transcriptional regulation of aldosterone-regulated genes. Design and Methods: Four MR mutations affecting residues in the ligand binding domain, identified in families with PHA1, were tested. MR proteins generated by site-directed mutagenesis were analyzed for their binding to aldosterone and were transiently transfected into renal cells to explore the functional effects on the transcriptional activity of the receptors by cis-trans-cotrans-activation assays and by measuring the induction of endogenous gene transcription. Results: Binding assays showed very low or absent aldosterone binding for mutants MR(877Pro), MR(848Pro), and MR(947stop) and decreased affinity for aldosterone of MR(843Pro). Compared with wildtype MR, the mutations p.Leu843Pro and p.Leu877Pro displayed half-maximal aldosterone-dependent transactivation of reporter genes driven by mouse mammary tumor virus or glucocorticoid response element-2 dependent promoters, whereas MR(848Pro) and MR(947stop) nearly or completely lost transcriptional activity. Although MR(848Pro) and MR(947stop) were also incapable of inducing aldosterone-dependent gene expression ofendogenoussgk1, GILZ, NDRG2, and SCNN1A, MR(843Pro) retained complete transcriptional activity on sgk1 and GILZ gene expression, and MR(877Pro) negatively affected the expression of sgk1, NDRG2, and SCNN1A. Conclusions: Our data demonstrate that MR mutations differentially affect individual gene expression in a promoter-dependent manner. Investigation of differential gene expression profiles in PHA1 may allow a better understanding of the molecular substrate of phenotypic variability and to elucidate pathogenic mechanisms underlying the disease. (J Clin Endocrinol Metab 96: E519-E527, 2011)

Modeling the Dynamics of Viral Evolution Considering Competition Within Individual Hosts and at Population Level: The Effects of Treatment

We consider two viral strains competing against each other within individual hosts (at cellular level) and at population level (for infecting hosts) by studying two cases. In the first case, the strains do not mutate into each other. In this case, we found that each individual in the population can be infected by only one strain and that co-existence in the population is possible only when the strain that has the greater basic intracellular reproduction number, R (0c) , has the smaller population number R (0p) . Treatment against the one strain shifts the population equilibrium toward the other strain in a complicated way (see Appendix B). In the second case, we assume that the strain that has the greater intracellular number R (0c) can mutate into the other strain. In this case, individual hosts can be simultaneously infected by both strains (co-existence within the host). Treatment shifts the prevalence of the two strains within the hosts, depending on the mortality induced by the treatment, which is, in turn, dependent upon the doses given to each individual. The relative proportions of the strains at the population level, under treatment, depend both on the relative proportions within the hosts (which is determined by the dosage of treatment) and on the number of individuals treated per unit time, that is, the rate of treatment. Implications for cases of real diseases are briefly discussed.

Effects of individual housing on behavior and resistance to Ehrlich tumor growth in mice

This study analyzed in Balb/C mice the effects of individual housing on behavior, serum corticosterone and resistance to Ehrlich tumor growth. Mice (60 days old) were individually (IH) or grouped housed (G) (10-12 animals/cage) for 14-21 days. The 1st day of the housing condition was considered experimental day 1 (ED1). Results showed that on ED21, IH mice, when compared to G mice, presented no differences on corticosterone serum levels when kept undisturbed; however, an increased level of this hormone was observed in IH mice after an immobilization stress challenge. An increased time spent in the plus-maze closed arms and a decreased time in the open arms were also observed in IH mice. When compared to G animals, after inoculation with 105 Ehrlich tumor cells on ED1, IH mice presented an increase in volume of ascitic fluid and number of tumor cells. The survival time of IH mice was also shorter than that measured in G animals. Furthermore, IH mice injected with a different number of tumor cells on ED1 always presented increased Ehrlich tumor cells than G group. Interestingly. these effects were not observed when the tumor cells injection was done on ED4. These results suggest that individual-housing conditions induce an altered immune-endocrine response and, at the same time, decrease animals` resistance to Ehrlich tumor growth. It is proposed that the neural link between the behavioral and immunological changes observed after the stress of individual housing might involve the activation of the HPA axis. (C) 2008 Elsevier Inc. All rights reserved.

Environmental and Individual Factors Associated with Nail Fluoride Concentration

Nails have been suggested as suitable biomarkers of exposure to F, with the advantage of being easily obtained. The effect of water F concentration, age, gender, nail growth rate and geographical area on the F concentration in the fingernail and toenail clippings were evaluated. Volunteers (n = 300) aged 3-7, 14-20, 30-40 and 50-60 years from five Brazilian communities (A-E) participated. Drinking water and nail samples were collected and F concentration was analyzed with the electrode. A reference mark was made on each nail and growth rates were calculated. Data were analyzed by ANOVA and linear regression (alpha = 0.05). Mean water F concentrations (8 SE, mg/l) were 0.09 +/- 0.01, 0.15 +/- 0.01, 0.66 +/- 0.01, 0.72 +/- 0.02, and 1.68 +/- 0.08 for A-E, respectively. Mean F concentrations (+/- SE, mg/kg) ranged between 1.38 +/- 0.14 (A, 50-60 years) and 10.20 +/- 2.35 (D, 50-60 years) for fingernails, and between 0.92 +/- 0.08 (A, 14-20 years) and 7.35 +/- 0.80 (E, 50-60 years) for toenails. Among the tested factors, geographical area and water F concentration exerted the most influence on finger- and toenail F concentrations. Subjects of older age groups (30-40 and 50-60 years) from D and E showed higher nail F concentrations than the others. Females presented higher nail F concentration than males. Water F concentration, age, gender and geographical area influenced the F concentration of finger- and toenails, and hence should be taken into account when using this biomarker of exposure to predict risk for dental fluorosis. Copyright (C) 2009 S. Karger AG, Basel

Inequalities in dental services utilization among Brazilian low-income children: the role of individual determinants

Objectives: To assess the role of the individual determinants on the inequalities of dental services utilization among low-income children living in the working area of Brazilian`s federal Primary Health Care program, which is called Family Health Program (FHP), in a big city in Southern Brazil. Methods: A cross-sectional population-based study was performed. The sample included 350 children, ages 0 to 14 years, whose parents answered a questionnaire about their socioeconomic conditions, perceived needs, oral hygiene habits, and access to dental services. The data analysis was performed according to a conceptual framework based on Andersen`s behavioral model of health services use. Multivariate models of logistic regression analysis instructed the hypothesis on covariates for never having had a dental visit. Results: Thirty one percent of the surveyed children had never had a dental visit. In the bivariate analysis, higher proportion of children who had never had a dental visit was found among the very young, those with inadequate oral hygiene habits, those without perceived need of dental care, and those whose family homes were under absent ownership. The mechanisms of social support showed to be important enabling factors: children attending schools/kindergartens and being regularly monitored by the FHP teams had higher odds of having gone to the dentist, even after adjusting for socioeconomic, demographic, and need variables. Conclusions: The conceptual framework has confirmed the presence of social and psychosocial inequalities on the utilization pattern of dental services for low-income children. The individual determinants seem to be important predictors of access.

Assessment of inbreeding depression in a Guzerat dairy herd: Effects of individual increase in inbreeding coefficients on production and reproduction

Influences of inbreeding on daily milk yield (DMY), age at first calving (AFC), and calving intervals (CI) were determined on a highly inbred zebu dairy subpopulation of the Guzerat breed. Variance components were estimated using animal models in single-trait analyses. Two approaches were employed to estimate inbreeding depression: using individual increase in inbreeding coefficients or using inbreeding coefficients as possible covariates included in the statistical models. The pedigree file included 9,915 animals, of which 9,055 were inbred, with an average inbreeding coefficient of 15.2%. The maximum inbreeding coefficient observed was 49.45%, and the average inbreeding for the females still in the herd during the analysis was 26.42%. Heritability estimates were 0.27 for DMY and 0.38 for AFC. The genetic variance ratio estimated with the random regression model for CI ranged around 0.10. Increased inbreeding caused poorer performance in DMY, AFC, and CI. However, some of the cows with the highest milk yield were among the highly inbred animals in this subpopulation. Individual increase in inbreeding used as a covariate in the statistical models accounted for inbreeding depression while avoiding overestimation that may result when fitting inbreeding coefficients.

Nested diets: a novel pattern of individual-level resource use

Many generalist populations may actually be composed of relatively specialist individuals. This `individual specialization` may have important ecological and evolutionary implications. Although this phenomenon has been documented in more than one hundred taxa, it is still unclear how individuals within a population actually partition resources. Here we applied several methods based on network theory to investigate the intrapopulation patterns of resource use in the gracile mouse opossum Gracilinanus microtarsus. We found evidence of significant individual specialization in this species and that the diets of specialists are nested within the diets of generalists. This novel pattern is consistent with a recently proposed model of optimal foraging and implies strong asymmetry in the interactions among individuals of a population.

The nested assembly of individual-resource networks

P>1. Much of the current understanding of ecological systems is based on theory that does not explicitly take into account individual variation within natural populations. However, individuals may show substantial variation in resource use. This variation in turn may be translated into topological properties of networks that depict interactions among individuals and the food resources they consume (individual-resource networks). 2. Different models derived from optimal diet theory (ODT) predict highly distinct patterns of trophic interactions at the individual level that should translate into distinct network topologies. As a consequence, individual-resource networks can be useful tools in revealing the incidence of different patterns of resource use by individuals and suggesting their mechanistic basis. 3. In the present study, using data from several dietary studies, we assembled individual-resource networks of 10 vertebrate species, previously reported to show interindividual diet variation, and used a network-based approach to investigate their structure. 4. We found significant nestedness, but no modularity, in all empirical networks, indicating that (i) these populations are composed of both opportunistic and selective individuals and (ii) the diets of the latter are ordered as predictable subsets of the diets of the more opportunistic individuals. 5. Nested patterns are a common feature of species networks, and our results extend its generality to trophic interactions at the individual level. This pattern is consistent with a recently proposed ODT model, in which individuals show similar rank preferences but differ in their acceptance rate for alternative resources. Our findings therefore suggest a common mechanism underlying interindividual variation in resource use in disparate taxa.

Decomposition of spectral density in individual eigenvalue contributions

The eigenvalue densities of two random matrix ensembles, the Wigner Gaussian matrices and the Wishart covariant matrices, are decomposed in the contributions of each individual eigenvalue distribution. It is shown that the fluctuations of all eigenvalues, for medium matrix sizes, are described with a good precision by nearly normal distributions.