Genotype calling in tetraploid species from bi-allelic marker data using mixture models

<p>Abstract</p> <p>Background</p> <p>Automated genotype calling in tetraploid species was until recently not possible, which hampered genetic analysis. Modern genotyping assays often produce two signals, one for each allele of a bi-allelic marker. While ample software is available to obtain genotypes (homozygous for either allele, or heterozygous) for diploid species from these signals, such software is not available for tetraploid species which may be scored as five alternative genotypes (aaaa, baaa, bbaa, bbba and bbbb; nulliplex to quadruplex).</p> <p>Results</p> <p>We present a novel algorithm, implemented in the R package fitTetra, to assign genotypes for bi-allelic markers to tetraploid samples from genotyping assays that produce intensity signals for both alleles. The algorithm is based on the fitting of several mixture models with five components, one for each of the five possible genotypes. The models have different numbers of parameters specifying the relation between the five component means, and some of them impose a constraint on the mixing proportions to conform to Hardy-Weinberg equilibrium (HWE) ratios. The software rejects markers that do not allow a reliable genotyping for the majority of the samples, and it assigns a missing score to samples that cannot be scored into one of the five possible genotypes with sufficient confidence.</p> <p>Conclusions</p> <p>We have validated the software with data of a collection of 224 potato varieties assayed with an Illumina GoldenGate™ 384 SNP array and shown that all SNPs with informative ratio distributions are fitted. Almost all fitted models appear to be correct based on visual inspection and comparison with diploid samples. When the collection of potato varieties is analyzed as if it were a population, almost all markers seem to be in Hardy-Weinberg equilibrium. The R package fitTetra is freely available under the GNU Public License from <url>http://www.plantbreeding.wur.nl/UK/software_fitTetra.html</url> and as Additional files with this article.</p

Interpretation and Visualization of Non-Linear Data Fusion in Kernel Space: Study on Metabolomic Characterization of Progression of Multiple Sclerosis

Contains fulltext : 93904.pdf (publisher's version ) (Open Access

Genome-Wide Profile of Pleural Mesothelioma versus Parietal and Visceral Pleura: The Emerging Gene Portrait of the Mesothelioma Phenotype

Malignant pleural mesothelioma is considered an almost incurable tumour with increasing incidence worldwide. It usually develops in the parietal pleura, from mesothelial lining or submesothelial cells, subsequently invading the visceral pleura. Chromosomal and genomic aberrations of mesothelioma are diverse and heterogenous. Genome-wide profiling of mesothelioma versus parietal and visceral normal pleural tissue could thus reveal novel genes and pathways explaining its aggressive phenotype.Well-characterised tissue from five mesothelioma patients and normal parietal and visceral pleural samples from six non-cancer patients were profiled by Affymetrix oligoarray of 38 500 genes. The lists of differentially expressed genes tested for overrepresentation in KEGG PATHWAYS (Kyoto Encyclopedia of Genes and Genomes) and GO (gene ontology) terms revealed large differences of expression between visceral and parietal pleura, and both tissues differed from mesothelioma. Cell growth and intrinsic resistance in tumour versus parietal pleura was reflected in highly overexpressed cell cycle, mitosis, replication, DNA repair and anti-apoptosis genes. Several genes of the “salvage pathway” that recycle nucleobases were overexpressed, among them TYMS, encoding thymidylate synthase, the main target of the antifolate drug pemetrexed that is active in mesothelioma. Circadian rhythm genes were expressed in favour of tumour growth. The local invasive, non-metastatic phenotype of mesothelioma, could partly be due to overexpression of the known metastasis suppressors NME1 and NME2. Down-regulation of several tumour suppressor genes could contribute to mesothelioma progression. Genes involved in cell communication were down-regulated, indicating that mesothelioma may shield itself from the immune system. Similarly, in non-cancer parietal versus visceral pleura signal transduction, soluble transporter and adhesion genes were down-regulated. This could represent a genetical platform of the parietal pleura propensity to develop mesothelioma.Genome-wide microarray approach using complex human tissue samples revealed novel expression patterns, reflecting some important features of mesothelioma biology that should be further explored

Genome-Wide association study (GWAS) for growth rate and age at sexual maturation in atlantic salmon (Salmo salar)

Early sexual maturation is considered a serious drawback for Atlantic salmon aquaculture as it retards growth, increases production times and affects flesh quality. Although both growth and sexual maturation are thought to be complex processes controlled by several genetic and environmental factors, selection for these traits has been continuously accomplished since the beginning of Atlantic salmon selective breeding programs. In this genome-wide association study (GWAS) we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype ∼480 individuals from the Cermaq Canada broodstock program and search for SNPs associated with growth and age at sexual maturation. Using a mixed model approach we identified markers showing a significant association with growth, grilsing (early sexual maturation) and late sexual maturation. The most significant associations were found for grilsing, with markers located in Ssa10, Ssa02, Ssa13, Ssa25 and Ssa12, and for late maturation with markers located in Ssa28, Ssa01 and Ssa21. A lower level of association was detected with growth on Ssa13. Candidate genes, which were linked to these genetic markers, were identified and some of them show a direct relationship with developmental processes, especially for those in association with sexual maturation. However, the relatively low power to detect genetic markers associated with growth (days to 5 kg) in this GWAS indicates the need to use a higher density SNP array in order to overcome the low levels of linkage disequilibrium observed in Atlantic salmon before the information can be incorporated into a selective breeding program