@article{KneitzMishraChalopinetal.2016, author = {Kneitz, Susanne and Mishra, Rasmi R. and Chalopin, Domitille and Postlethwait, John and Warren, Wesley C. and Walther, Ronald B. and Schartl, Manfred}, title = {Germ cell and tumor associated piRNAs in the medaka and \(Xiphophorus\) melanoma models}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, number = {357}, doi = {10.1186/s12864-016-2697-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146028}, year = {2016}, abstract = {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.}, language = {en} } @article{RodriguezMariWilsonTitusetal.2011, author = {Rodr{\´i}guez-Mari, Adriana and Wilson, Catherine and Titus, Tom A. and Canestro, Cristian and BreMiller, Ruth A. and Yan, Yi-Lin and Nanda, Indrajit and Johnston, Adam and Kanki, John P. and Gray, Erin M. and He, Xinjun and Spitsbergen, Jan and Schindler, Detlev and Postlethwait, John H.}, title = {Roles of brca2 (fancd1) in Oocyte Nuclear Architecture, Gametogenesis, Gonad Tumors, and Genome Stability in Zebrafish}, series = {PLoS Genetics}, volume = {7}, journal = {PLoS Genetics}, number = {3}, doi = {10.1371/journal.pone.0026377}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142285}, pages = {e1001357}, year = {2011}, abstract = {Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: (25.0 +/- 2.8) years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V(gray)) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6 +/- 0.7) mm considering the deepest 5\% of light. Of the detected photon packages scalp and bone absorbed (96.4 +/- 9: 7)\% and V(gray) absorbed (3.1 +/- 1.8)\% of the energy. The mean V(gray) volume (1.1 +/- 0.4)cm(3) was negatively correlated (r = - .76) with the SCD and frontal sinus volume (r = - .57) and was reduced by 41.5\% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r = .46) and the traversed frontal sinus volume (r = .43). Sulcal morphology had no significant impact on V(gray). Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance.}, language = {en} } @article{DuWuertzAdolfietal.2019, author = {Du, Kang and Wuertz, Sven and Adolfi, Mateus and Kneitz, Susanne and St{\"o}ck, Matthias and Oliveira, Marcos and N{\´o}brega, Rafael and Ormanns, Jenny and Kloas, Werner and Feron, Romain and Klopp, Christophe and Parrinello, Hugues and Journot, Laurent and He, Shunping and Postlethwait, John and Meyer, Axel and Guiguen, Yann and Schartl, Manfred}, title = {The genome of the arapaima (Arapaima gigas) provides insights into gigantism, fast growth and chromosomal sex determination system}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-41457-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201333}, pages = {5293}, year = {2019}, abstract = {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.}, language = {en} } @article{SchartlWalterShenetal.2013, author = {Schartl, Manfred and Walter, Ronald B. and Shen, Yingjia and Garcia, Tzintzuni and Catchen, Julian and Amores, Angel and Braasch, Ingo and Chalopin, Domitille and Volff, Jean-Nicolas and Lesch, Klaus-Peter and Bisazza, Angelo and Minx, Pat and Hillier, LaDeana and Wilson, Richard K. and F{\"u}rstenberg, Susan and Boore, Jeffrey and Searle, Steve and Postlethwait, John H. and Warren, Wesley C.}, title = {The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaptation and several complex traits}, series = {Nature Genetics}, volume = {45}, journal = {Nature Genetics}, number = {5}, doi = {10.1038/ng.2604}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132152}, pages = {567-572}, year = {2013}, abstract = {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.}, language = {en} } @article{SchartlShenMaurusetal.2015, author = {Schartl, Manfred and Shen, Yingjia and Maurus, Katja and Walter, Ron and Tomlinson, Chad and Wilson, Richard K. and Postlethwait, John and Warren, Wesley C.}, title = {Whole body melanoma transcriptome response in medaka}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0143057}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144714}, pages = {e0143057}, year = {2015}, abstract = {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.}, language = {en} } @article{ShenChalopinGarciaetal.2016, author = {Shen, Yingjia and Chalopin, Domitille and Garcia, Tzintzuni and Boswell, Mikki and Boswell, William and Shiryev, Sergey A. and Agarwala, Richa and Volff, Jean-Nicolas and Postlethwait, John H. and Schartl, Manfred and Minx, Patrick and Warren, Wesley C. and Walter, Ronald B.}, title = {X. couchianus and X. hellerii genome models provide genomic variation insight among Xiphophorus species}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, doi = {10.1186/s12864-015-2361-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164582}, pages = {37}, year = {2016}, abstract = {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.}, language = {en} }