ENGINES: exploring single nucleotide variation in entire human genomes

<p>Abstract</p> <p>Background</p> <p>Next generation ultra-sequencing technologies are starting to produce extensive quantities of data from entire human genome or exome sequences, and therefore new software is needed to present and analyse this vast amount of information. The 1000 Genomes project has recently released raw data for 629 complete genomes representing several human populations through their Phase I interim analysis and, although there are certain public tools available that allow exploration of these genomes, to date there is no tool that permits comprehensive population analysis of the variation catalogued by such data.</p> <p>Description</p> <p>We have developed a genetic variant site explorer able to retrieve data for Single Nucleotide Variation (SNVs), population by population, from entire genomes without compromising future scalability and agility. ENGINES (ENtire Genome INterface for Exploring SNVs) uses data from the 1000 Genomes Phase I to demonstrate its capacity to handle large amounts of genetic variation (>7.3 billion genotypes and 28 million SNVs), as well as deriving summary statistics of interest for medical and population genetics applications. The whole dataset is pre-processed and summarized into a data mart accessible through a web interface. The query system allows the combination and comparison of each available population sample, while searching by rs-number list, chromosome region, or genes of interest. Frequency and F_STfilters are available to further refine queries, while results can be visually compared with other large-scale Single Nucleotide Polymorphism (SNP) repositories such as HapMap or Perlegen.</p> <p>Conclusions</p> <p>ENGINES is capable of accessing large-scale variation data repositories in a fast and comprehensive manner. It allows quick browsing of whole genome variation, while providing statistical information for each variant site such as allele frequency, heterozygosity or F_STvalues for genetic differentiation. Access to the data mart generating scripts and to the web interface is granted from <url>http://spsmart.cesga.es/engines.php</url></p

Goldstini Can Give the Higgs a Boost

Supersymmetric collider phenomenology depends crucially on whether the lightest observable-sector supersymmetric particle (LOSP) decays, and if so, what the LOSP decay products are. For instance, in SUSY models where the gravitino is lighter than the LOSP, the LOSP decays to its superpartner and a longitudinal gravitino via supercurrent couplings. In this paper, we show that LOSP decays can be substantially modified when there are multiple sectors that break supersymmetry, where in addition to the gravitino there are light uneaten goldstini. As a particularly striking example, a bino-like LOSP can have a near 100% branching fraction to a higgs boson and an uneaten goldstino, even if the LOSP has negligible higgsino fraction. This occurs because the uneaten goldstino is unconstrained by the supercurrent, allowing additional operators to mediate LOSP decay. These operators can be enhanced in the presence of an R symmetry, leading to copious boosted higgs production in SUSY cascade decays.Comment: 30 pages, 12 figures; v2: title change, clarifications added, version to appear in JHE

Absence of disparities in anthropometric measures among Chilean indigenous and non-indigenous newborns

<p>Abstract</p> <p>Background</p> <p>Studies throughout North America and Europe have documented adverse perinatal outcomes for racial/ethnic minorities. Nonetheless, the contrast in newborn characteristics between indigenous and non-indigenous populations in Latin America has been poorly characterized. This is due to many challenges, including a lack of vital registration information on ethnicity. The objective of this study was to analyze trends in anthropometric measures at birth in Chilean indigenous (Mapuche) and non-indigenous children over a 5-year period.</p> <p>Methods</p> <p>We examined weight and length at birth using information available through a national data base of all birth records for the years 2000 through 2004 (n = 1,166.513). Newborns were classified ethnically according to the origins of the parents' last names.</p> <p>Result</p> <p>The average birthweight was stable over the 5 year period with variations of less than 20 g in each group, and with mean values trivially higher in indigenous newborns. The proportion weighing less than 2500 g at birth increased modestly from 5.2% to 5.6% in non-indigenous newborns whereas the indigenous births remained constant at 5.2%. In multiple regression analyses, adjusting flexibly for gestational age and maternal characteristics, the occurrence of an indigenous surname added only 14 g to an average infant's birthweight while holding other factors constant. Results for length at birth were similar, and adjusted time trend variation in both outcomes was trivially small after adjustment. Anthropometric indexes at birth in Chile are quite favorable by international standards.</p> <p>Conclusion</p> <p>There is only a trivial degree of ethnic disparity in these values, in contrast to conditions for ethnic minorities in other countries. Moreover, these values remained roughly constant over the 5 years of observation in this study.</p

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

Validation of a Cost-Efficient Multi-Purpose SNP Panel for Disease Based Research

BACKGROUND: Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA "barcoding" to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies. PRINCIPAL FINDINGS: Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the "barcode." Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel. CONCLUSION: The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists

Insulin Resistance in Chileans of European and Indigenous Descent: Evidence for an Ethnicity x Environment Interaction

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Effects of urbanisation on diabetes risk appear to be greater in indigenous populations worldwide than in populations of European origin, but the reasons are unclear. This cross-sectional study aimed to determine whether the effects of environment (Rural vs. Urban), adiposity, fitness and lifestyle variables on insulin resistance differed between individuals of indigenous Mapuche origin compared to those of European origin in Chile.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; 123 Rural Mapuche, 124 Urban Mapuche, 91 Rural European and 134 Urban European Chilean adults had blood taken for determination of HOMA-estimated insulin resistance (HOMA(IR)) and underwent assessment of physical activity/sedentary behaviour (using accelerometry), cardiorespiratory fitness, dietary intake and body composition. General linear models were used to determine interactions with ethnicity for key variables. There was a significant "ethnicity x environment" interaction for HOMA(IR) (Mean +/- SD; Rural Mapuche: 1.65 +/- 2.03, Urban Mapuche: 4.90 +/- 3.05, Rural European: 0.82 +/- 0.61, Urban European: 1.55 +/- 1.34, p((interaction)) = 0.0003), such that the effect of urbanisation on HOMA(IR) was greater in Mapuches than Europeans. In addition, there were significant interactions (all p&lt;0.004) with ethnicity for effects of adiposity, sedentary time and physical activity on HOMA(IR), with greater effects seen in Mapuches compared to Europeans, an observation that persisted after adjustment for potential confounders.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; Urbanisation, adiposity, physical activity and sedentary behaviour influence insulin resistance to a greater extent in Chilean Mapuches than Chileans of European descent. These findings have implications for the design and implementation of lifestyle strategies to reduce metabolic risk in different ethnic groups, and for understanding of the mechanisms underpinning human insulin resistance.&lt;/p&gt

Prevalence of insulin resistance and its association with metabolic syndrome criteria among Bolivian children and adolescents with obesity

<p>Abstract</p> <p>Background</p> <p>Obesity is a one of the most common nutritional disorder worldwide, clearly associated with the metabolic syndrome, condition with implications for the development of many chronic diseases.</p> <p>In the poorest countries of Latin America, malnourishment is still the most prevalent nutritional problem, but obesity is emerging in alarming rates over the last 10 years without a predictable association with metabolic syndrome.</p> <p>The objective of our study was to determine the association between insulin-resistance and components of the metabolic syndrome in a group of Bolivian obese children and adolescents. The second objective was determining the relation of acanthosis nigricans and insulin-resistance.</p> <p>Methods</p> <p>We studied 61 obese children and adolescents aged between 5 and 18 years old. All children underwent an oral glucose tolerance test and fasting blood sample was also obtained to measure insulin, HDL, LDL and triglycerides serum level. The diagnosis of metabolic syndrome was defined according to National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III) criteria adapted for children.</p> <p>Results</p> <p>Metabolic syndrome was found in 36% of the children, with a higher rate among males (40%) than females (32.2%) (p = 0.599). The prevalence of each of the components was 8.2% in impaired glucose tolerance, 42.6% for high triglyceride level, 55.7% for low levels of high-density lipoprotein cholesterol, and 24.5% for high blood pressure. Insulin resistance (HOMA-IR > 3.5) was found in 39.4% of the children, with a higher rate in males (50%) than females (29%). A strong correlation was found between insulin resistance and high blood pressure (p = 0.0148) and high triglycerides (p = 0.002). No statistical significance was found between the presence of acanthosis nigricans and insulin resistance.</p> <p>Conclusion</p> <p>Metabolic syndrome has a prevalence of 36% in children and adolescent population in the study. Insulin resistance was very common among children with obesity with a significant association with high blood pressure and high triglycerides presence.</p

Optimizing the procedure of grain nutrient predictions in barley via hyperspectral imaging

Hyperspectral imaging enables researchers and plant breeders to analyze various traits of interest like nutritional value in high throughput. In order to achieve this, the optimal design of a reliable calibration model, linking the measured spectra with the investigated traits, is necessary. In the present study we investigated the impact of different regression models, calibration set sizes and calibration set compositions on prediction performance. For this purpose, we analyzed concentrations of six globally relevant grain nutrients of the wild barley population HEB-YIELD as case study. The data comprised 1,593 plots, grown in 2015 and 2016 at the locations Dundee and Halle, which have been entirely analyzed through traditional laboratory methods and hyperspectral imaging. The results indicated that a linear regression model based on partial least squares outperformed neural networks in this particular data modelling task. There existed a positive relationship between the number of samples in a calibration model and prediction performance, with a local optimum at a calibration set size of ~40% of the total data. The inclusion of samples from several years and locations could clearly improve the predictions of the investigated nutrient traits at small calibration set sizes. It should be stated that the expansion of calibration models with additional samples is only useful as long as they are able to increase trait variability. Models obtained in a certain environment were only to a limited extent transferable to other environments. They should therefore be successively upgraded with new calibration data to enable a reliable prediction of the desired traits. The presented results will assist the design and conceptualization of future hyperspectral imaging projects in order to achieve reliable predictions. It will in general help to establish practical applications of hyperspectral imaging systems, for instance in plant breeding concepts