11674
2014
eng
44
15
article
1
2015-07-25
--
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A multicopy Y-chromosomal SGNH hydrolase gene expressed in the testis of the platyfish has been captured and mobilized by a Helitron transposon
Background: Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfish Xiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed.
Results: A novel three-copy gene called teximY (for testis-expressed in Xiphophorus maculatus on the Y) was identified on the Y but not on the X chromosome. A highly related sequence called texim1, probably at the origin of the Y-linked genes, as well as three more divergent texim genes were detected in (pseudo) autosomal regions of the platyfish genome. Texim genes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases. Texim gene distribution is patchy in animals. Texim sequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish. Texim-like genes are also present in Oikopleura (urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly, texim genes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestral texim gene in the bony fish lineage. RT-qPCR analyses showed that Y-linked teximY genes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata).
Conclusions: These observations suggest either that TeximY proteins play a role in Helitron transposition in the male germ line in fish, or that texim genes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.
BMC Genetics
10.1186/1471-2156-15-44
24712907
urn:nbn:de:bvb:20-opus-116746
BMC Genetics 2014 15:44. doi:10.1186/1471-2156-15-44
Marta Tomaszkiewicz
Domitille Chalopin
Manfred Schartl
Delphine Galiana
Jean-Nicolas Volff
eng
uncontrolled
sex determination
eng
uncontrolled
testis
eng
uncontrolled
Y chromosome
eng
uncontrolled
rolling-circle transposons
eng
uncontrolled
factor acetylhydrolase activity
eng
uncontrolled
platelet activation factor
eng
uncontrolled
xiphophorus maculatus
eng
uncontrolled
oryzias-latipes
eng
uncontrolled
sequence alignment
eng
uncontrolled
DM-domain gene
eng
uncontrolled
sex-determining region
eng
uncontrolled
evolution
eng
uncontrolled
fish
eng
uncontrolled
SGNH hydrolase
eng
uncontrolled
helitron
eng
uncontrolled
transposition
eng
uncontrolled
platyfish
eng
uncontrolled
sex chromosomes
Medizin und Gesundheit
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11674/091_Tomaszkiewicz_BMC_GENETICS.pdf
11991
2014
eng
2
7
article
1
2015-10-07
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Beyond the zebrafish: diverse fish species for modeling human disease
In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.
Disease Models & Mechanisms
10.1242/dmm.012245
1754-8411
urn:nbn:de:bvb:20-opus-119919
Disease Models & Mechanisms (2014) 7, 181-192 doi:10.1242/dmm.012245
Manfred Schartl
eng
uncontrolled
evolutionary mutant model
eng
uncontrolled
natural variation
eng
uncontrolled
cancer
eng
uncontrolled
fish model
Physiologie und verwandte Themen
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11991/066_Schartl_Disease_Models_&_Mechanisms.pdf
12064
2014
eng
5040-53
13
5
article
1
2015-10-21
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--
The MAPK pathway as an apoptosis enhancer in melanoma
Inhibition of RAF/MEK/ERK signaling is beneficial for many patients with BRAFV600E–mutated melanoma. However, primary and secondary resistances restrict long-lasting therapy success. Combination therapies are therefore urgently needed. Here, we evaluate the cellular effect of combining a MEK inhibitor with a genotoxic apoptosis inducer. Strikingly, we observed that an activated MAPK pathway promotes in several melanoma cell lines the pro-apoptotic response to genotoxic stress, and MEK inhibition reduces intrinsic apoptosis. This goes along with MEK inhibitor induced increased RAS and P-AKT levels. The protective effect of the MEK inhibitor depends on PI3K signaling, which prevents the induction of pro-apoptotic PUMA that mediates apoptosis after DNA damage. We could show that the MEK inhibitor dependent feedback loop is enabled by several factors, including EGF receptor and members of the SPRED family. The simultaneous knockdown of SPRED1 and SPRED2 mimicked the effects of MEK inhibitor such as PUMA repression and protection from apoptosis. Our data demonstrate that MEK inhibition of BRAFV600E-positive melanoma cells can protect from genotoxic stress, thereby achieving the opposite of the intended anti-tumorigenic effect of the combination of MEK inhibitor with inducers of intrinsic apoptosis.
Oncotarget
1949-2553
urn:nbn:de:bvb:20-opus-120649
Oncotarget, Vol. 5, No. 13, 5040-53
Johannes M. Haydn
Anita Hufnagel
Johannes Grimm
Katja Maurus
Manfred Schartl
Svenja Meierjohann
eng
uncontrolled
PI3K
eng
uncontrolled
melanoma
eng
uncontrolled
RAS
eng
uncontrolled
chemotherapy resistance
eng
uncontrolled
crosstalk
Pharmakologie, Therapeutik
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12064/110_Hydn_Oncotarget.pdf
11600
2014
eng
e100250
6
9
article
1
2015-07-16
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Novel Method for Analysis of Allele Specific Expression in Triploid Oryzias latipes Reveals Consistent Pattern of Allele Exclusion
Assessing allele-specific gene expression (ASE) on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types) and diseased tissues (trisomies, non-disjunction events, cancerous tissues). In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82%) shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18%) displayed a wide range of ASE levels. Interestingly the majority of genes (78%) displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.
PLOS ONE
10.1371/journal.pone.0100250
1932-6203
24945156
urn:nbn:de:bvb:20-opus-116000
PLoS ONE 9(6): e100250. doi:10.1371/journal.pone.0100250
Tzintzuni I. Garcia
Isa Matos
Yingjia Shen
Vagmita Pabuwal
Maria Manuela Coelho
Yuko Wakamatsu
Manfred Schartl
Ronald B. Walter
eng
uncontrolled
RNA-SEQ data
eng
uncontrolled
copy-number alteration
eng
uncontrolled
squalius alburnoides
eng
uncontrolled
gene expression
eng
uncontrolled
medaka
eng
uncontrolled
variant detection
eng
uncontrolled
transplantation
eng
uncontrolled
genome
eng
uncontrolled
generation
eng
uncontrolled
evolution
Medizin und Gesundheit
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11600/070_Garcia_PLOS_ONE.pdf