TY - JOUR A1 - Cerezo-Echevarria, Argiñe A1 - Kehl, Alexandra A1 - Beitzinger, Christoph A1 - Müller, Tobias A1 - Klopfleisch, Robert A1 - Aupperle-Lellbach, Heike T1 - Evaluating the histologic grade of digital squamous cell carcinomas in dogs and copy number variation of KIT Ligand — a correlation study JF - Veterinary Sciences N2 - Dark-haired dogs are predisposed to the development of digital squamous cell carcinoma (DSCC). This may potentially suggest an underlying genetic predisposition not yet completely elucidated. Some authors have suggested a potential correlation between the number of copies KIT Ligand (KITLG) and the predisposition of dogs to DSCC, containing a higher number of copies in those affected by the neoplasm. In this study, the aim was to evaluate a potential correlation between the number of copies of the KITLG and the histological grade of malignancy in dogs with DSCC. For this, 72 paraffin-embedded DSCCs with paired whole blood samples of 70 different dogs were included and grouped according to their haircoat color as follow: Group 0/unknown haircoat color (n = 11); Group 1.a/black non-Schnauzers (n = 15); group 1.b/black Schnauzers (n = 33); group 1.c/black and tan dogs (n = 7); group 2/tan animals (n = 4). The DSCCs were histologically graded. Additionally, KITLG Copy Number Variation (CNV) was determined by ddPCR. A significant correlation was observed between KITLG copy number and the histological grade and score value. This finding may suggest a possible factor for the development of canine DSCC, thus potentially having an impact on personalized veterinary oncological strategies and breeding programs. KW - canine KW - cancer KW - toe KW - grading KW - haircoat KW - color KW - genetics KW - gene Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304824 SN - 2306-7381 VL - 10 IS - 2 ER - TY - JOUR A1 - Appel, Mirjam A1 - Scholz, Claus-Jürgen A1 - Müller, Tobias A1 - Dittrich, Marcus A1 - König, Christian A1 - Bockstaller, Marie A1 - Oguz, Tuba A1 - Khalili, Afshin A1 - Antwi-Adjei, Emmanuel A1 - Schauer, Tamas A1 - Margulies, Carla A1 - Tanimoto, Hiromu A1 - Yarali, Ayse T1 - Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster JF - PLoS ONE N2 - Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/or sequences covaried with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance- associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hairlike organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms. KW - functional analysis KW - disruption project KW - natural variation KW - complex traits KW - networks KW - behavior KW - flies KW - temperature KW - genetics KW - painful Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152006 VL - 10 IS - 5 ER - TY - JOUR A1 - Kühnisch, Jirko A1 - Herbst, Christopher A1 - Al‐Wakeel‐Marquard, Nadya A1 - Dartsch, Josephine A1 - Holtgrewe, Manuel A1 - Baban, Anwar A1 - Mearini, Giulia A1 - Hardt, Juliane A1 - Kolokotronis, Konstantinos A1 - Gerull, Brenda A1 - Carrier, Lucie A1 - Beule, Dieter A1 - Schubert, Stephan A1 - Messroghli, Daniel A1 - Degener, Franziska A1 - Berger, Felix A1 - Klaassen, Sabine T1 - Targeted panel sequencing in pediatric primary cardiomyopathy supports a critical role of TNNI3 JF - Clinical Genetics N2 - The underlying genetic mechanisms and early pathological events of children with primary cardiomyopathy (CMP) are insufficiently characterized. In this study, we aimed to characterize the mutational spectrum of primary CMP in a large cohort of patients ≤18 years referred to a tertiary center. Eighty unrelated index patients with pediatric primary CMP underwent genetic testing with a panel‐based next‐generation sequencing approach of 89 genes. At least one pathogenic or probably pathogenic variant was identified in 30/80 (38%) index patients. In all CMP subgroups, patients carried most frequently variants of interest in sarcomere genes suggesting them as a major contributor in pediatric primary CMP. In MYH7, MYBPC3, and TNNI3, we identified 18 pathogenic/probably pathogenic variants (MYH7 n = 7, MYBPC3 n = 6, TNNI3 n = 5, including one homozygous (TNNI3 c.24+2T>A) truncating variant. Protein and transcript level analysis on heart biopsies from individuals with homozygous mutation of TNNI3 revealed that the TNNI3 protein is absent and associated with upregulation of the fetal isoform TNNI1. The present study further supports the clinical importance of sarcomeric mutation—not only in adult—but also in pediatric primary CMP. TNNI3 is the third most important disease gene in this cohort and complete loss of TNNI3 leads to severe pediatric CMP. KW - cardiomyopathy KW - genetics KW - pediatrics KW - sarcomere KW - TNNI3 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213958 VL - 96 IS - 6 SP - 549 EP - 559 ER - TY - JOUR A1 - Künstner, Axel A1 - Hoffmann, Margarete A1 - Fraser, Bonnie A. A1 - Kottler, Verena A. A1 - Sharma, Eshita A1 - Weigel, Detlef A1 - Dreyer, Christine T1 - The Genome of the Trinidadian Guppy, Poecilia reticulata, and Variation in the Guanapo Population JF - PLoS ONE N2 - For over a century, the live bearing guppy, Poecilia reticulata, has been used to study sexual selection as well as local adaptation. Natural guppy populations differ in many traits that are of intuitively adaptive significance such as ornamentation, age at maturity, brood size and body shape. Water depth, light supply, food resources and predation regime shape these traits, and barrier waterfalls often separate contrasting environments in the same river. We have assembled and annotated the genome of an inbred single female from a high-predation site in the Guanapo drainage. The final assembly comprises 731.6 Mb with a scaffold N50 of 5.3 MB. Scaffolds were mapped to linkage groups, placing 95% of the genome assembly on the 22 autosomes and the X-chromosome. To investigate genetic variation in the population used for the genome assembly, we sequenced 10 wild caught male individuals. The identified 5 million SNPs correspond to an average nucleotide diversity (π) of 0.0025. The genome assembly and SNP map provide a rich resource for investigating adaptation to different predation regimes. In addition, comparisons with the genomes of other Poeciliid species, which differ greatly in mechanisms of sex determination and maternal resource allocation, as well as comparisons to other teleost genera can begin to reveal how live bearing evolved in teleost fish. KW - Trinidadian guppy KW - Poecilia reticulata KW - genetics Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166755 VL - 11 IS - 12 ER - TY - JOUR A1 - Merget, Benjamin A1 - Koetschan, Christian A1 - Hackl, Thomas A1 - Förster, Frank A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Schultz, Jörg A1 - Wolf, Matthias T1 - The ITS2 Database JF - Journal of Visual Expression N2 - The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation. The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold. The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure. In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses. KW - homology modeling KW - molecular systematics KW - internal transcribed spacer 2 KW - alignment KW - genetics KW - secondary structure KW - ribosomal RNA KW - phylogenetic tree KW - phylogeny Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124600 VL - 61 IS - e3806 ER - TY - JOUR A1 - Poethke, Hans J. A1 - Pfenning, Brenda A1 - Hovestadt, Thomas T1 - The relative contribution of individual and kin selection to the evolution of density-dependent dispersal rates N2 - Questions: What are the relative contributions of kin selection and individual selection to the evolution of dispersal rates in fragmented landscapes? How do environmental parameters influence the relative contributions of both evolutionary forces? Features of the model: Individual-based simulation model of a metapopulation. Logistic local growth dynamics and density-dependent dispersal. An optional shuffling algorithm allows the continuous destruction of any genetic structure in the metapopulation. Ranges of key variables: Depending on dispersal mortality (0.05-0.4) and the strength of environmental fluctuations, mean dispersal probability varied between 0.05 and 0.5. Conclusions: For local population sizes of 100 individuals, kin selection alone could account for dispersal probabilities of up to 0.1. It may result in a ten-fold increase of optimal dispersal rates compared with those predicted on the basis of individual selection alone. Such a substantial contribution of kin selection to dispersal is restricted to cases where the overall dispersal probabilities are small (textless 0.1). In the latter case, as much as 30% of the total fitness of dispersing individuals could arise from the increased reproduction of kin left in the natal patch. KW - dispersal rate KW - dynamics KW - environmental correlation KW - evolutionary modelling KW - genetics KW - individual-based model KW - kin competition Y1 - 2007 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-48225 ER -