"GenotypeColour™": colour visualisation of SNPs and CNVs

<p>Abstract</p> <p>Background</p> <p>The volume of data available on genetic variations has increased considerably with the recent development of high-density, single-nucleotide polymorphism (SNP) arrays. Several software programs have been developed to assist researchers in the analysis of this huge amount of data, but few can rely upon a whole genome variability visualisation system that could help data interpretation.</p> <p>Results</p> <p>We have developed <it>GenotypeColour™ </it>as a rapid user-friendly tool able to upload, visualise and compare the huge amounts of data produced by Affymetrix Human Mapping GeneChips without losing the overall view of the data.</p> <p>Some features of <it>GenotypeColour™ </it>include visualising the entire genome variability in a single screenshot for one or more samples, the simultaneous display of the genotype and Copy Number state for thousands of SNPs, and the comparison of large amounts of samples by producing "consensus" images displaying regions of complete or partial identity. The software is also useful for genotype analysis of trios and to show regions of potential uniparental disomy (UPD). All information can then be exported in a tabular format for analysis with dedicated software. At present, the software can handle data from 10 K, 100 K, 250 K, 5.0 and 6.0 Affymetrix chips.</p> <p>Conclusion</p> <p>We have created a software that offers a new way of displaying and comparing SNP and CNV genomic data. The software is available free at <url>http://www.med.unibs.it/~barlati/GenotypeColour</url> and is especially useful for the analysis of multiple samples.</p

Computational modelling of emboli travel trajectories in cerebral arteries: Influence of microembolic particle size and density

This article has been made available through the Brunel Open Access Publishing Fund.Ischaemic stroke is responsible for up to 80 % of stroke cases. Prevention of the reoccurrence of ischaemic attack or stroke for patients who survived the first symptoms is the major treatment target. Accurate diagnosis of the emboli source for a specific infarction lesion is very important for a better treatment for the patient. However, due to the complex blood flow patterns in the cerebral arterial network, little is known so far of the embolic particle flow trajectory and its behaviour in such a complex flow field. The present study aims to study the trajectories of embolic particles released from carotid arteries and basilar artery in a cerebral arterial network and the influence of particle size, mass and release location to the particle distributions, by computational modelling. The cerebral arterial network model, which includes major arteries in the circle of Willis and several generations of branches from them, was generated from MRI images. Particles with diameters of 200, 500 and 800 μ m and densities of 800, 1,030 and 1,300 kg/m 3 were released in the vessel's central and near-wall regions. A fully coupled scheme of particle and blood flow in a computational fluid dynamics software ANASYS CFX 13 was used in the simulations. The results show that heavy particles (density large than blood or a diameter larger than 500 μ m) normally have small travel speeds in arteries; larger or lighter embolic particles are more likely to travel to large branches in cerebral arteries. In certain cases, all large particles go to the middle cerebral arteries; large particles with higher travel speeds in large arteries are likely to travel at more complex and tortuous trajectories; emboli raised from the basilar artery will only exit the model from branches of basilar artery and posterior cerebral arteries. A modified Circle of Willis configuration can have significant influence on particle distributions. The local branch patterns of internal carotid artery to middle cerebral artery and anterior communicating artery can have large impact on such distributions. © 2014 The Author(s)

Till death (or an intruder) do us part: intrasexual-competition in a monogamous Primate

Polygynous animals are often highly dimorphic, and show large sex-differences in the degree of intra-sexual competition and aggression, which is associated with biased operational sex ratios (OSR). For socially monogamous, sexually monomorphic species, this relationship is less clear. Among mammals, pair-living has sometimes been assumed to imply equal OSR and low frequency, low intensity intra-sexual competition; even when high rates of intra-sexual competition and selection, in both sexes, have been theoretically predicted and described for various taxa. Owl monkeys are one of a few socially monogamous primates. Using long-term demographic and morphological data from 18 groups, we show that male and female owl monkeys experience intense intra-sexual competition and aggression from solitary floaters. Pair-mates are regularly replaced by intruding floaters (27 female and 23 male replacements in 149 group-years), with negative effects on the reproductive success of both partners. Individuals with only one partner during their life produced 25% more offspring per decade of tenure than those with two or more partners. The termination of the pair-bond is initiated by the floater, and sometimes has fatal consequences for the expelled adult. The existence of floaters and the sporadic, but intense aggression between them and residents suggest that it can be misleading to assume an equal OSR in socially monogamous species based solely on group composition. Instead, we suggest that sexual selection models must assume not equal, but flexible, context-specific, OSR in monogamous species.Wenner-Gren Foundation, L.S.B. Leakey Foundation, the National Geographic Society, National Science Foundation (BCS- 0621020), the University of Pennsylvania Research Foundation and the Zoological Society of San Diego, German Science Foundation (HU 1746-2/1

Inferring introduction routes of invasive species using approximate Bayesian computation on microsatellite data

Determining the routes of introduction provides not only information about the history of an invasion process, but also information about the origin and construction of the genetic composition of the invading population. It remains difficult, however, to infer introduction routes from molecular data because of a lack of appropriate methods. We evaluate here the use of an approximate Bayesian computation (ABC) method for estimating the probabilities of introduction routes of invasive populations based on microsatellite data. We considered the crucial case of a single source population from which two invasive populations originated either serially from a single introduction event or from two independent introduction events. Using simulated datasets, we found that the method gave correct inferences and was robust to many erroneous beliefs. The method was also more efficient than traditional methods based on raw values of statistics such as assignment likelihood or pairwise F(ST). We illustrate some of the features of our ABC method, using real microsatellite datasets obtained for invasive populations of the western corn rootworm, Diabrotica virgifera virgifera. Most computations were performed with the DIYABC program (http://www1.montpellier.inra.fr/CBGP/diyabc/)

Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans

We studied seven genes that reflect events relevant to antidepressant action at four sequential levels: (1) entry into the brain, (2) binding to monoaminergic transporters, and (3) distal effects at the transcription level, resulting in (4) changes in neurotrophin and neuropeptide receptors. Those genes are ATP-binding cassette subfamily B member 1 (ABCB1), the noradrenaline, dopamine, and serotonin transporters (SLC6A2, SLC6A3 and SLC6A4), cyclic AMP-responsive element binding protein 1 (CREB1), corticotropin-releasing hormone receptor 1 (CRHR1) and neurotrophic tyrosine kinase type 2 receptor (NTRK2). Sequence variability for those genes was obtained in exonic and flanking regions. A total of 56 280 000 bp across were sequenced in 536 unrelated Mexican Americans from Los Angeles (264 controls and 272 major depressive disorder (MDD)). We detected in those individuals 419 single nucleotide polymorphisms (SNPs); the nucleotide diversity was 0.00054±0.0001. Of those, a total of 204 novel SNPs were identified, corresponding to 49% of all previously reported SNPs in those genes: 72 were in untranslated regions, 19 were in coding sequences of which 7 were non-synonymous, 86 were intronic and 27 were in upstream/downstream regions. Several SNPs or haplotypes in ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1 and NTRK2 were associated with MDD, and in ABCB1, SLC6A2 and NTRK2 with antidepressant response. After controlling for age, gender and baseline 21-item Hamilton Depression Rating Scale (HAM-D21) score, as well as correcting for multiple testing, the relative reduction of HAM-D21 score remained significantly associated with two NTRK2-coding SNPs (rs2289657 and rs56142442) and the haplotype CAG at rs2289658 (splice site), rs2289657 and rs2289656. Further studies in larger independent samples will be needed to confirm these associations. Our data indicate that extensive assessment of sequence variability may contribute to increase understanding of disease susceptibility and drug response. Moreover, these results highlight the importance of direct re-sequencing of key candidate genes in ethnic minority groups in order to discover novel genetic variants that cannot be simply inferred from existing databases

Islet Formation during the Neonatal Development in Mice

The islet of Langerhans is a unique micro-organ within the exocrine pancreas, which is composed of insulin-secreting beta-cells, glucagon-secreting alpha-cells, somatostatin-secreting delta-cells, pancreatic polypeptide-secreting PP cells and ghrelin-secreting epsilon-cells. Islets also contain non-endocrine cell types such as endothelial cells. However, the mechanism(s) of islet formation is poorly understood due to technical difficulties in capturing this dynamic event in situ. We have developed a method to monitor beta-cell proliferation and islet formation in the intact pancreas using transgenic mice in which the beta-cells are specifically tagged with a fluorescent protein. Endocrine cells proliferate contiguously, forming branched cord-like structures in both embryos and neonates. Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas. Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets. We propose that islet formation occurs by a process of fission following contiguous endocrine cell proliferation, rather than by local aggregation or fusion of isolated beta-cells and islets. Mathematical modeling of the fission process in the neonatal islet formation is also presented

Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

Molecular diversity of anthracnose pathogen populations associated with UK strawberry production suggests multiple introductions of three different Colletotrichum species.

Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

High levels of genetic variability and differentiation in hilsa shad, Tenualosa ilisha (Clupeidae, Clupeiformes) populations revealed by PCR-RFLP analysis of the mitochondrial DNA D-loop region

The hilsa shad, Tenualosa ilisha (Clupeidae, Clupeiformes) is an important anadromous clupeid species from the Western division of the Indo-Pacific region. It constitutes the largest single fishable species in Bangladesh. Information on genetic variability and population structure is very important for both management and conservation purposes. Past reports on the population structure of T. ilisha involving morphometric, allozyme and RAPD analyses are contradictory. We examined genetic variability and divergence in two riverine (the Jamuna and the Meghna), two estuarine (Kuakata and Sundarbans) and one marine (Cox's Bazar) populations of T. ilisha by applying PCR-RFLP analysis of the mtDNA D-loop region. The amplified PCR products were restricted with four restriction enzymes namely, XbaI, EcoRI, EcoRV, and HaeIII. High levels of haplotype and gene diversity within and significant differentiations among, populations of T. ilisha were observed in this study. Significant FST values indicated differentiation among the river, estuary and marine populations. The UPGMA dendrogram based on genetic distance resulted in two major clusters, although, these were subsequently divided into three, corresponding to the riverine, estuarine and marine populations. The study underlines the usefulness of RFLP of mtDNA D-loop region as molecular markers, and detected at least two differentiated populations of T. ilisha in Bangladesh waters