Системний підхід у соціальній адаптації студентів-іноземців

SUMMARY: High-throughput genotyping and sequencing technologies facilitate studies of complex genetic traits and provide new research opportunities. The increasing popularity of genome-wide association studies (GWAS) leads to the discovery of new associated loci and a better understanding of the genetic architecture underlying not only diseases, but also other monogenic and complex phenotypes. Several softwares are available for performing GWAS analyses, R environment being one of them. RESULTS: We present cgmisc, an R package that enables enhanced data analysis and visualisation of results from GWAS. The package contains several utilities and modules that complement and enhance the functionality of the existing software. It also provides several tools for advanced visualisation of genomic data and utilises the power of the R language to aid in preparation of publication-quality figures. Some of the package functions are specific for the domestic dog (Canis familiaris) data. AVAILABILITY: The package is operating system-independent and is available from: https://github.com/cgmisc-team/cgmisc CONTACT: [email protected]

Genetical genomics: spotlight on QTL hotspots

No abstract available

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

MAPfastR: Quantitative Trait Loci Mapping in Outbred Line Crosses

MAPfastR is a software package developed to analyze quantitative trait loci data from inbred and outbred line-crosses. The package includes a number of modules for fast and accurate quantitative trait loci analyses. It has been developed in the R language for fast and comprehensive analyses of large datasets. MAPfastR is freely available at: http://www.computationalgenetics.se/?page_id=7.Swedish Foundation for Strategic Research (Future Research Leader program), European Science Foundation (EURYI Award)

A general and efficient method for estimating continuous IBD functions for use in genome scans for QTL

<p>Abstract</p> <p>Background</p> <p>Identity by descent (IBD) matrix estimation is a central component in mapping of Quantitative Trait Loci (QTL) using variance component models. A large number of algorithms have been developed for estimation of IBD between individuals in populations at discrete locations in the genome for use in genome scans to detect QTL affecting various traits of interest in experimental animal, human and agricultural pedigrees. Here, we propose a new approach to estimate IBD as continuous functions rather than as discrete values.</p> <p>Results</p> <p>Estimation of IBD functions improved the computational efficiency and memory usage in genome scanning for QTL. We have explored two approaches to obtain continuous marker-bracket IBD-functions. By re-implementing an existing and fast deterministic IBD-estimation method, we show that this approach results in IBD functions that produces the exact same IBD as the original algorithm, but with a greater than 2-fold improvement of the computational efficiency and a considerably lower memory requirement for storing the resulting genome-wide IBD. By developing a general IBD function approximation algorithm, we show that it is possible to estimate marker-bracket IBD functions from IBD matrices estimated at marker locations by any existing IBD estimation algorithm. The general algorithm provides approximations that lead to QTL variance component estimates that even in worst-case scenarios are very similar to the true values. The approach of storing IBD as polynomial IBD-function was also shown to reduce the amount of memory required in genome scans for QTL.</p> <p>Conclusion</p> <p>In addition to direct improvements in computational and memory efficiency, estimation of IBD-functions is a fundamental step needed to develop and implement new efficient optimization algorithms for high precision localization of QTL. Here, we discuss and test two approaches for estimating IBD functions based on existing IBD estimation algorithms. Our approaches provide immediately useful techniques for use in single QTL analyses in the variance component QTL mapping framework. They will, however, be particularly useful in genome scans for multiple interacting QTL, where the improvements in both computational and memory efficiency are the key for successful development of efficient optimization algorithms to allow widespread use of this methodology.</p

The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε

Replication fork stalling and accumulation of single-stranded DNA trigger the S phase checkpoint, a signalling cascade that, in budding yeast, leads to the activation of the Rad53 kinase. Rad53 is essential in maintaining cell viability, but its targets of regulation are still partially unknown. Here we show that Rad53 drives the hyper-SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε, principally following replication forks stalling induced by nucleotide depletion. Pol2 is the main target of SUMOylation within the replisome and its modification requires the SUMO-ligase Mms21, a subunit of the Smc5/6 complex. Moreover, the Smc5/6 complex co-purifies with Pol ε, independently of other replisome components. Finally, we map Pol2 SUMOylation to a single site within the N-terminal catalytic domain and identify a SUMO-interacting motif at the C-terminus of Pol2. These data suggest that the S phase checkpoint regulate Pol ε during replication stress through Pol2 SUMOylation and SUMO-binding abilit

The influence of hydrological regimes on sex ratios and spatial segregation of the sexes in two dioecious riparian shrub species in northern Sweden

River management practices have altered the hydrological regimes of many rivers and also altered the availability of regeneration niches for riparian species. We investigated the impact of changed hydrological regimes on the sex ratios and the Spatial Segregation of the Sexes (SSS) in the dioecious species Salix myrsinifolia Salisb.–phylicifolia L. and S. lapponum L. by studying the free-flowing Vindel River and the regulated Ume River in northern Sweden. We surveyed sex ratios of these species in 12 river reaches on the Vindel River and in 17 reaches on the Ume River. In addition, we surveyed the sex and location above mean river stage of 1,002 individuals across both river systems to investigate the SSS of both species. Cuttings were collected from male and female individuals of S. myrsinifolia–phylicifolia from both rivers and subjected to four different water table regimes in a greenhouse experiment to investigate growth response between the sexes. We found an M/F sex ratio in both river systems similar to the regional norm of 0.62 for S. myrsinifolia–phylicifolia and of 0.42 for S. lapponum. We found no evidence of SSS in either the free-flowing Vindel River or the regulated Ume River. In the greenhouse experiment, hydrological regime had a significant effect on shoot and root dry weight and on root length. Significantly higher shoot dry weights were found in females than in males and significantly different shoot and root dry weights were found between cuttings taken from the two rivers. We concluded that changed hydrological regimes are likely to alter dimensions of the regeneration niche and therefore to influence sex ratios and SSS at an early successional stage, making it difficult to find clear spatial patterns once these species reach maturity and can be sexed

qtl.outbred: Interfacing outbred line cross data with the R/qtl mapping software

<p>Abstract</p> <p>Background</p> <p><b>qtl.outbred </b>is an extendible interface in the statistical environment, R, for combining quantitative trait loci (QTL) mapping tools. It is built as an umbrella package that enables outbred genotype probabilities to be calculated and/or imported into the software package R/<b>qtl</b>.</p> <p>Findings</p> <p>Using <b>qtl.outbred</b>, the genotype probabilities from outbred line cross data can be calculated by interfacing with a new and efficient algorithm developed for analyzing arbitrarily large datasets (included in the package) or imported from other sources such as the web-based tool, GridQTL.</p> <p>Conclusion</p> <p><b>qtl.outbred </b>will improve the speed for calculating probabilities and the ability to analyse large future datasets. This package enables the user to analyse outbred line cross data accurately, but with similar effort than inbred line cross data.</p

A complete classification of epistatic two-locus models

Background: The study of epistasis is of great importance in statistical genetics in fields such as linkage and association analysis and QTL mapping. In an effort to classify the types of epistasis in the case of two biallelic loci Li and Reich listed and described all models in the simplest case of 0/ 1 penetrance values. However, they left open the problem of finding a classification of two-locus models with continuous penetrance values. Results: We provide a complete classification of biallelic two-locus models. In addition to solving the classification problem for dichotomous trait disease models, our results apply to any instance where real numbers are assigned to genotypes, and provide a complete framework for studying epistasis in QTL data. Our approach is geometric and we show that there are 387 distinct types of two-locus models, which can be reduced to 69 when symmetry between loci and alleles is accounted for. The model types are defined by 86 circuits, which are linear combinations of genotype values, each of which measures a fundamental unit of interaction. Conclusion: The circuits provide information on epistasis beyond that contained in the additive × additive, additive × dominance, and dominance × dominance interaction terms. We discuss th

How To Perform Meaningful Estimates of Genetic Effects

Although the genotype-phenotype map plays a central role both in Quantitative and Evolutionary Genetics, the formalization of a completely general and satisfactory model of genetic effects, particularly accounting for epistasis, remains a theoretical challenge. Here, we use a two-locus genetic system in simulated populations with epistasis to show the convenience of using a recently developed model, NOIA, to perform estimates of genetic effects and the decomposition of the genetic variance that are orthogonal even under deviations from the Hardy-Weinberg proportions. We develop the theory for how to use this model in interval mapping of quantitative trait loci using Halley-Knott regressions, and we analyze a real data set to illustrate the advantage of using this approach in practice. In this example, we show that departures from the Hardy-Weinberg proportions that are expected by sampling alone substantially alter the orthogonal estimates of genetic effects when other statistical models, like F2 or G2A, are used instead of NOIA. Finally, for the first time from real data, we provide estimates of functional genetic effects as sets of effects of natural allele substitutions in a particular genotype, which enriches the debate on the interpretation of genetic effects as implemented both in functional and in statistical models. We also discuss further implementations leading to a completely general genotype-phenotype map