Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-14602 Wissenschaftlicher Artikel Kneitz, Susanne; Mishra, Rasmi R.; Chalopin, Domitille; Postlethwait, John; Warren, Wesley C.; Walther, Ronald B.; Schartl, Manfred Germ cell and tumor associated piRNAs in the medaka and \(Xiphophorus\) melanoma models Background A growing number of studies report an abnormal expression of Piwi-interacting RNAs (piRNAs) and the piRNA processing enzyme Piwi in many cancers. Whether this finding is an epiphenomenon of the chaotic molecular biology of the fast dividing, neoplastically transformed cells or is functionally relevant to tumorigenesisis is difficult to discern at present. To better understand the role of piRNAs in cancer development small laboratory fish models can make a valuable contribution. However, little is known about piRNAs in somatic and neoplastic tissues of fish. Results To identify piRNA clusters that might be involved in melanoma pathogenesis, we use several transgenic lines of medaka, and platyfish/swordtail hybrids, which develop various types of melanoma. In these tumors Piwi, is expressed at different levels, depending on tumor type. To quantify piRNA levels, whole piRNA populations of testes and melanomas of different histotypes were sequenced. Because no reference piRNA cluster set for medaka or Xiphophorus was yet available we developed a software pipeline to detect piRNA clusters in our samples and clusters were selected that were enriched in one or more samples. We found several loci to be overexpressed or down-regulated in different melanoma subtypes as compared to hyperpigmented skin. Furthermore, cluster analysis revealed a clear distinction between testes, low-grade and high-grade malignant melanoma in medaka. Conclusions Our data imply that dysregulation of piRNA expression may be associated with development of melanoma. Our results also reinforce the importance of fish as a suitable model system to study the role of piRNAs in tumorigenesis. 2016 BMC Genomics 17 357 urn:nbn:de:bvb:20-opus-146028 10.1186/s12864-016-2697-z Theodor-Boveri-Institut für Biowissenschaften OPUS4-13215 Wissenschaftlicher Artikel Schartl, Manfred; Walter, Ronald B.; Shen, Yingjia; Garcia, Tzintzuni; Catchen, Julian; Amores, Angel; Braasch, Ingo; Chalopin, Domitille; Volff, Jean-Nicolas; Lesch, Klaus-Peter; Bisazza, Angelo; Minx, Pat; Hillier, LaDeana; Wilson, Richard K.; Fürstenberg, Susan; Boore, Jeffrey; Searle, Steve; Postlethwait, John H.; Warren, Wesley C. The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaptation and several complex traits Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in lower vertebrates. The genetic mechanisms underlying the evolution of these elaborate traits are poorly understood. The platyfish, X. maculatus, offers a unique model to better understand the molecular biology of such traits. We report here the sequencing of the platyfish genome. Integrating genome assembly with extensive genetic maps identified an unexpected evolutionary stability of chromosomes in fish, in contrast to in mammals. Genes associated with viviparity show signatures of positive selection, identifying new putative functional domains and rare cases of parallel evolution. We also find that genes implicated in cognition show an unexpectedly high rate of duplicate gene retention after the teleost genome duplication event, suggesting a hypothesis for the evolution of the behavioral complexity in fish, which exceeds that found in amphibians and reptiles. 2013 567-572 Nature Genetics 45 5 urn:nbn:de:bvb:20-opus-132152 10.1038/ng.2604 Institut für Humangenetik OPUS4-14471 Wissenschaftlicher Artikel Schartl, Manfred; Shen, Yingjia; Maurus, Katja; Walter, Ron; Tomlinson, Chad; Wilson, Richard K.; Postlethwait, John; Warren, Wesley C. Whole body melanoma transcriptome response in medaka The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. 2015 e0143057 PLoS ONE 10 12 urn:nbn:de:bvb:20-opus-144714 10.1371/journal.pone.0143057 Theodor-Boveri-Institut für Biowissenschaften OPUS4-16458 Wissenschaftlicher Artikel Shen, Yingjia; Chalopin, Domitille; Garcia, Tzintzuni; Boswell, Mikki; Boswell, William; Shiryev, Sergey A.; Agarwala, Richa; Volff, Jean-Nicolas; Postlethwait, John H.; Schartl, Manfred; Minx, Patrick; Warren, Wesley C.; Walter, Ronald B. X. couchianus and X. hellerii genome models provide genomic variation insight among Xiphophorus species Background Xiphophorus fishes are represented by 26 live-bearing species of tropical fish that express many attributes (e.g., viviparity, genetic and phenotypic variation, ecological adaptation, varied sexual developmental mechanisms, ability to produce fertile interspecies hybrids) that have made attractive research models for over 85 years. Use of various interspecies hybrids to investigate the genetics underlying spontaneous and induced tumorigenesis has resulted in the development and maintenance of pedigreed Xiphophorus lines specifically bred for research. The recent availability of the X. maculatus reference genome assembly now provides unprecedented opportunities for novel and exciting comparative research studies among Xiphophorus species. Results We present sequencing, assembly and annotation of two new genomes representing Xiphophorus couchianus and Xiphophorus hellerii. The final X. couchianus and X. hellerii assemblies have total sizes of 708 Mb and 734 Mb and correspond to 98 % and 102 % of the X. maculatus Jp 163 A genome size, respectively. The rates of single nucleotide change range from 1 per 52 bp to 1 per 69 bp among the three genomes and the impact of putatively damaging variants are presented. In addition, a survey of transposable elements allowed us to deduce an ancestral TE landscape, uncovered potential active TEs and document a recent burst of TEs during evolution of this genus. Conclusions Two new Xiphophorus genomes and their corresponding transcriptomes were efficiently assembled, the former using a novel guided assembly approach. Three assembled genome sequences within this single vertebrate order of new world live-bearing fishes will accelerate our understanding of relationship between environmental adaptation and genome evolution. In addition, these genome resources provide capability to determine allele specific gene regulation among interspecies hybrids produced by crossing any of the three species that are known to produce progeny predisposed to tumor development. 2016 37 BMC Genomics 17 urn:nbn:de:bvb:20-opus-164582 10.1186/s12864-015-2361-z Theodor-Boveri-Institut für Biowissenschaften OPUS4-20133 Wissenschaftlicher Artikel Du, Kang; Wuertz, Sven; Adolfi, Mateus; Kneitz, Susanne; Stöck, Matthias; Oliveira, Marcos; Nóbrega, Rafael; Ormanns, Jenny; Kloas, Werner; Feron, Romain; Klopp, Christophe; Parrinello, Hugues; Journot, Laurent; He, Shunping; Postlethwait, John; Meyer, Axel; Guiguen, Yann; Schartl, Manfred The genome of the arapaima (Arapaima gigas) provides insights into gigantism, fast growth and chromosomal sex determination system We have sequenced the genome of the largest freshwater fish species of the world, the arapaima. Analysis of gene family dynamics and signatures of positive selection identified genes involved in the specific adaptations and unique features of this iconic species, in particular it's large size and fast growth. Genome sequences from both sexes combined with RAD-tag analyses from other males and females led to the isolation of male-specific scaffolds and supports an XY sex determination system in arapaima. Whole transcriptome sequencing showed that the product of the gland-like secretory organ on the head surface of males and females may not only provide nutritional fluid for sex-unbiased parental care, but that the organ itself has a more specific function in males, which engage more in parental care. 2019 5293 Scientific Reports 9 urn:nbn:de:bvb:20-opus-201333 10.1038/s41598-019-41457-x Theodor-Boveri-Institut für Biowissenschaften