Evaluation of genetic diversity between 27 banana cultivars (Musa spp.) in Mauritius using RAPD markers

Cultivated bananas (Musa spp.) are mostly diploid or triploid cultivars with various combinations of the A and B genomes inherited from their diploid ancestors Musa acuminata Colla. and Musa balbisianaColla. respectively. Random amplified polymorphic DNA (RAPD) markers were used to establish the relatedness of 27 accessions in the Mauritian Musa germplasm. 15 decamer primers produced a total of115 reproducible amplification products, of which 96 were polymorphic. Computation of the genetic distances shows that similarities ranged from 0.3 to 1.0 with an average of 0.51. With a few exceptions,cluster analysis differentiated pure A containing cultivars from those containing at least one B genome. This paper answers long standing questions on the taxonomic placement of the cultivar ‘BananeRouge’ by providing the basis for its classification within the homogenomic A cultivars. The results presented here also contribute to narrowing the gaps in our current understanding of the migration path of bananas and the emergence of secondary centers of diversity

Inference of disease associations with unmeasured genetic variants by combining results from genome-wide association studies with linkage disequilibrium patterns in a reference data set

Results from whole-genome association studies of many common diseases are now available. Increasingly, these are being incorporated into meta-analyses to increase the power to detect weak associations with measured single-nucleotide polymorphisms (SNPs). Imputation of genotypes at unmeasured loci has been widely applied using patterns of linkage disequilibrium (LD) observed in the HapMap panels, but there is a need for alternative methods that can utilize the pooled effect estimates from meta-analyses and explore possible associations with SNPs and haplotypes that are not included in HapMap

Significance of sex in achieving sustained remission in the consortium of rheumatology researchers of north america cohort of rheumatoid arthritis patients

Objective To determine whether men with rheumatoid arthritis (RA) are more likely to achieve remission compared to women. Methods RA patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) cohort between October 2001 and January 2010 were selected for the present analyses. Detailed clinical, demographic, and drug utilization data were available at enrollment (baseline) and at subsequent followup visits. We examined the influence of sex on the Clinical Disease Activity Index remission score (≤2.8) using sustained remission or point remission as the primary outcome measure in multivariate stepwise logistic regression models. We stratified the data by RA duration at baseline (≤2 years or >2 years) to investigate whether RA duration had differential effects on remission in men and women. Results A total of 10,299 RA patients (2,406 men and 7,893 women) were available for this study. In both early and established RA, women had more severe disease at baseline with worse disease activity measures, modified Health Assessment Questionnaire disability index score, pain on a visual analog scale, and depression. Women were also more likely to have been treated with disease‐modifying antirheumatic drugs and anti–tumor necrosis factor therapy compared to men. In the regression models, male sex was associated with sustained remission in early RA (odds ratio [OR] 1.38, 95% confidence interval [95% CI] 1.07–1.78, P = 0.01), but not in established RA. However, for point remission, an inverse association was observed with male sex in established RA (OR 0.65, 95% CI 0.48–0.87, P = 0.005) and not in early RA. Conclusion Within the large real‐life CORRONA cohort of RA patients, men were more likely to achieve sustained remission compared to women in early RA, although not in established RA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94462/1/21762_ftp.pd

A user-centred evaluation framework for the Sealife semantic web browsers

Background: Semantically-enriched browsing has enhanced the browsing experience by providing contextualised dynamically generated Web content, and quicker access to searched-for information. However, adoption of Semantic Web technologies is limited and user perception from the non-IT domain sceptical. Furthermore, little attention has been given to evaluating semantic browsers with real users to demonstrate the enhancements and obtain valuable feedback. The Sealife project investigates semantic browsing and its application to the life science domain. Sealife's main objective is to develop the notion of context-based information integration by extending three existing Semantic Web browsers (SWBs) to link the existing Web to the eScience infrastructure. / Methods: This paper describes a user-centred evaluation framework that was developed to evaluate the Sealife SWBs that elicited feedback on users' perceptions on ease of use and information findability. Three sources of data: i) web server logs; ii) user questionnaires; and iii) semi-structured interviews were analysed and comparisons made between each browser and a control system. / Results: It was found that the evaluation framework used successfully elicited users' perceptions of the three distinct SWBs. The results indicate that the browser with the most mature and polished interface was rated higher for usability, and semantic links were used by the users of all three browsers. / Conclusion: Confirmation or contradiction of our original hypotheses with relation to SWBs is detailed along with observations of implementation issues

BigDL: A Distributed Deep Learning Framework for Big Data

This paper presents BigDL (a distributed deep learning framework for Apache Spark), which has been used by a variety of users in the industry for building deep learning applications on production big data platforms. It allows deep learning applications to run on the Apache Hadoop/Spark cluster so as to directly process the production data, and as a part of the end-to-end data analysis pipeline for deployment and management. Unlike existing deep learning frameworks, BigDL implements distributed, data parallel training directly on top of the functional compute model (with copy-on-write and coarse-grained operations) of Spark. We also share real-world experience and "war stories" of users that have adopted BigDL to address their challenges(i.e., how to easily build end-to-end data analysis and deep learning pipelines for their production data).Comment: In ACM Symposium of Cloud Computing conference (SoCC) 201

Issues in the management of simple and complex meconium ileus

Various surgical methods are used to treat meconium ileus (MI), including resection with enterostomy (RES), primary anastomosis (RPA), and purse-string enterotomy with intra-operative lavage (PSI). The aim of this study is to discuss the surgical treatment of MI, based on our experience. Of the 41 MI patients treated at our institution between 1984 and 2007, 18 had simple MI and 23 had complex MI. These groups were analyzed according to treatment modality, concentrating on length of hospital stay, complications [peritonitis, septicemia, adhesive small bowel obstruction (ASBO), and malabsorption/diarrhea], need for additional surgical procedures, mortality. Of the 18 patients with simple MI, 7 (39%) were successfully treated with diluted Gastrografin® enema. The remaining 11 patients were treated surgically: two underwent RPA, of whom one died; five had RES, of whom one developed ASBO; four underwent PSI, of whom two developed peritonitis. In the complex MI group, 14 patients underwent RPA, with peritonitis occurring in three (one died); nine underwent RES, of whom two developed ASBO. In patients with simple MI, conservative treatment with diluted Gastrografin® enema is an effective initial treatment in our hands. In case of failure, RES is advisable. Patients with complex MI are candidates for RES. RPA and PSI seem to have higher complication rate

Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis

Genome-wide association studies (GWAS) conducted using commercial single nucleotide polymorphisms (SNP) arrays have proven to be a powerful tool for the detection of common disease susceptibility variants. However, their utility for the detection of lower frequency variants is yet to be practically investigated. Here we describe the application of a rare variant collapsing method to a large genome-wide SNP dataset, the Wellcome Trust Case Control Consortium rheumatoid arthritis (RA) GWAS. We partitioned the data into gene-centric bins and collapsed genotypes of low frequency variants (defined here as MAF ≤0.05) into a single count coupled with univariate analysis. We then prioritised gene regions for further investigation in an independent cohort of 3,355 cases and 2,427 controls based on rare variant signal p value and prior evidence to support involvement in RA. A total of 14,536 gene bins were investigated in the primary analysis and signals mapping to the TNFAIP3 and chr17q24 loci were selected for further investigation. We detected replicating association to low frequency variants in the TNFAIP3 gene (combined p = 6.6 × 10−6). Even though rare variants are not well-represented and can be difficult to genotype in GWAS, our study supports the application of low frequency variant collapsing methods to genome-wide SNP datasets as a means of exploiting data that are routinely ignored

A Genome-Wide Homozygosity Association Study Identifies Runs of Homozygosity Associated with Rheumatoid Arthritis in the Human Major Histocompatibility Complex

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a polygenic mode of inheritance. This study examined the hypothesis that runs of homozygosity (ROHs) play a recessive-acting role in the underlying RA genetic mechanism and identified RA-associated ROHs. Ours is the first genome-wide homozygosity association study for RA and characterized the ROH patterns associated with RA in the genomes of 2,000 RA patients and 3,000 normal controls of the Wellcome Trust Case Control Consortium. Genome scans consistently pinpointed two regions within the human major histocompatibility complex region containing RA-associated ROHs. The first region is from 32,451,664 bp to 32,846,093 bp (−log10(p)>22.6591). RA-susceptibility genes, such as HLA-DRB1, are contained in this region. The second region ranges from 32,933,485 bp to 33,585,118 bp (−log10(p)>8.3644) and contains other HLA-DPA1 and HLA-DPB1 genes. These two regions are physically close but are located in different blocks of linkage disequilibrium, and ∼40% of the RA patients' genomes carry these ROHs in the two regions. By analyzing homozygote intensities, an ROH that is anchored by the single nucleotide polymorphism rs2027852 and flanked by HLA-DRB6 and HLA-DRB1 was found associated with increased risk for RA. The presence of this risky ROH provides a 62% accuracy to predict RA disease status. An independent genomic dataset from 868 RA patients and 1,194 control subjects of the North American Rheumatoid Arthritis Consortium successfully validated the results obtained using the Wellcome Trust Case Control Consortium data. In conclusion, this genome-wide homozygosity association study provides an alternative to allelic association mapping for the identification of recessive variants responsible for RA. The identified RA-associated ROHs uncover recessive components and missing heritability associated with RA and other autoimmune diseases

Minor Abnormalities of Testis Development in Mice Lacking the Gene Encoding the MAPK Signalling Component, MAP3K1

In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD) have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase kinase 1, MAP3K1, a component of the mitogen-activated protein kinase (MAPK) signal transduction pathway. In individuals harbouring heterozygous mutations in MAP3K1, dysregulation of MAPK signalling was observed in lymphoblastoid cell lines, suggesting a causal role for these mutations in disrupting XY sexual development. Mice lacking the cognate gene, Map3k1, are viable and exhibit the eyes open at birth (EOB) phenotype on a mixed genetic background, but on the C57BL/6J genetic background most mice die at around 14.5 dpc due to a failure of erythropoiesis in the fetal liver. However, no systematic examination of sexual development in Map3k1-deficient mice has been described, an omission that is especially relevant in the case of C57BL/6J, a genetic background that is sensitized to disruptions to testis determination. Here, we report that on a mixed genetic background mice lacking Map3k1 are fertile and exhibit no overt abnormalities of testis development. On C57BL/6J, significant non-viability is observed with very few animals surviving to adulthood. However, an examination of development in Map3k1-deficient XY embryos on this genetic background revealed no significant defects in testis determination, although minor abnormalities were observed, including an increase in gonadal length. Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans