Lineage testing
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Karcinom ovaria je onemocnění s významnou dědičnou komponentou. Dědičnou mutaci v klinicky relevantních genech nacházíme v naší populaci u každé čtvrté pacientky. Proto je ke genetickému vyšetření zárodečných mutací indikována každá pacientka s tímto onemocněním (epiteliální zhoubný nádor vaječníku, vejcovodu nebo peritonea), bez ohledu na histopatologický typ tumoru ovaria či věk v době diagnózy. Genetické vyšetření má pro samotnou pacientku význam prognostický i prediktivní. U téměř každé páté nemocné (až 20 % všech pacientek s karcinomem ovaria) diagnostikujeme přítomnost patogenní zárodečné mutace v genech BRCA1 a BRCA2. Nosičky mutací v genech BRCA1 a BRCA2 zpravidla lépe odpovídají na léčbu platinovými deriváty, a tato léčba může být uplatněna i ve vyšších liniích. Genetické vyšetření zárodečných mutací navíc umožňuje cílené genetické poradenství v rodině pacientky, identifikaci osob v riziku a odpovídající dispenzarizaci nosičů mutace s cílem prevence / časné diagnostiky souvisejících nádorových onemocnění. Zárodečná, ale i somatická mutace genů BRCA1 a BRCA2 může také hrát roli v rozvaze o indikaci konkrétního inhibitoru poly-ADP-ribózapolymerázy (PARPi). Somatické mutace v BRCA1 a BRCA2 nacházíme u dalších 5-9 % žen s touto diagnózou. Souběžné vyšetření zárodečných a somatických mutací umožní zefektivnit identifikaci pacientek, které jsou potenciálními kandidátkami pro jeden z typů udržovací léčby PARPi, a zároveň odhalit zdravé příbuzné ve vysokém riziku vzniku především karcinomu prsu a ovaria.
Ovarian cancer is a disease with a significant hereditary component. Hereditary mutations in clinically relevant genes (including BRCA1 and BRCA2) are found in one in four patients in our population. Therefore, genetic testing for germline mutations is indicated for every patient with this disease (epithelial ovarian, fallopian tube or peritoneal cancer), regardless of the histopathological type of ovarian tumour or age at diagnosis. Nearly one in five patients (up to 20% of all patients with ovarian cancer) carries a pathogenic germline mutation in the BRCA1 and BRCA2 genes. Genetic testing has prognostic and predictive value for the patient herself. Carriers of mutations in the BRCA1 and BRCA2 genes generally respond better to treatment with platinum derivatives, and this treatment can be applied in higher lineages. In addition, genetic testing of germline mutations allows targeted genetic counselling in the patient`s family, identification of individuals at risk and appropriate surveillance management of the patient and her positively tested healthy relatives. Germline as well as somatic mutations in BRCA1 and BRCA2 genes may also play a role in the consideration of the indication of a specific poly-ADP-ribose polymerase inhibitor (PARPi). Somatic mutations in BRCA1 and BRCA2 are found in an additional 5-9% of women with ovarian cancer. Simultaneous testing for germline and somatic mutations will allow for more efficient identification of patients who are potential candidates for one type of PARPi maintenance therapy, while also detecting healthy relatives at high risk of developing breast and ovarian cancer in particular.
- MeSH
- genetická predispozice k nemoci MeSH
- genetické testování MeSH
- lidé MeSH
- nádory vaječníků * diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Over the past decades, the in vitro use of pluripotent cell lines gained a crucial role in toxicology, preclinical drug testing and developmental biology. NTERA2 clone D1 cells were identified as pluripotent cells with high potential for neural differentiation. Although they are commonly used cellular sources in neuropharmacology and neurodevelopmental studies, their endodermal and mesodermal differentiation potential awaits further characterization. Here, we devised improved protocols for hepatogenic and osteogenic differentiation of NTERA2 clone D1 cells. Our in vitro differentiation assays showed significant up-regulation of multiple hepatogenic markers. We also observed robust mineralization and osteogenic marker expression of NTERA2 clone D1 cells upon in vitro osteogenic induction. These results suggest that NTERA2 clone D1 cells may be utilized as an in vitro model system to study various aspects of liver biology and osteogenesis. In addition, tri-lineage differentiation of NTERA2 clone D1 cells may serve as a simple experimental control system when validating pluripotency of other cell types.
- MeSH
- buněčná diferenciace MeSH
- buněčné klony MeSH
- buněčné linie MeSH
- játra * MeSH
- osteogeneze * MeSH
- Publikační typ
- časopisecké články MeSH
Recent studies of the distribution and diversity of freshwater zooplankton have indicated that the previously understudied Eastern Palearctic region is an important biogeographic hotspot. Here, we explored the lineage diversity and reproductive modes of the Daphnia pulex species group across China. Members of this group are often keystone species of standing water bodies and are frequently used as a model system for ecological, evolutionary and, more recently, genomic studies. We found members of the D. pulex group in seven of seventy-six Chinese water bodies examined. We analyzed their phylogenetic position using mitochondrial markers, and explored the genetic structure of six populations using microsatellite markers. Mitochondrial DNA analysis suggested the presence of two distinct species complexes in China: the D. pulex complex that has a global distribution, and an apparently endemic Eastern Palearctic D. mitsukuri complex. Microsatellite analyses of six populations suggested that three of these reproduced by cyclical parthenogenesis, as evidenced by high clonal diversity and the absence of deviations from the Hardy-Weinberg equilibrium. In contrast, three other populations showed remarkably low diversity of multilocus genotypes. This suggests an obligate parthenogenetic reproductive mode, which was confirmed in one of the populations by comparison of genotypes of Daphnia adults and dormant embryos. All presumably obligate parthenogenetic clones were heterozygous at the majority of microsatellite loci, suggesting their hybrid origin. This was further supported by analyses of a small GTPase nuclear gene (rab4), as two alleles within single individuals belonged to different clades. Interestingly, one putatively obligate parthenogenetic clone carried three distinct alleles suggesting higher ploidy and potential gene flow between the D. pulicaria and D. mitsukuri complexes. Our data show that the expansion of the D. pulex complex in the Eastern Palearctic was associated with widespread hybridization.
- MeSH
- analýza hlavních komponent MeSH
- Daphnia klasifikace genetika MeSH
- fylogeneze * MeSH
- genetická variace * MeSH
- haplotypy MeSH
- jezera * MeSH
- mikrosatelitní repetice genetika MeSH
- mitochondriální DNA genetika MeSH
- mitochondriální geny MeSH
- pravděpodobnostní funkce MeSH
- rozmnožování genetika MeSH
- zeměpis MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Čína MeSH
Morphological and molecular evaluation of tapeworms of the genus Bothriocephalus Rudolphi, 1808 (Cestoda: Bothriocephalidea), based on newly collected and uniformly fixed worms from freshwater fishes in Canada and the United States has revealed unexpected diversity. With a combination of selected morphological features and 4 molecular markers (18S rDNA V8 region, ITS1, ITS2, and COI gene sequences), the following morphotypes and lineages of the Bothriocephalus cuspidatus Cooper, 1917 complex were identified, several of which are specific to their respective fish definitive hosts and may represent separate species: B. cuspidatus sensu stricto from walleye, Sander vitreus (type host), which likely includes a miniature morphotype from Johnny darter, Etheostoma nigrum (both Percidae); Bothriocephalus morphotype from pumpkinseed, Lepomis gibbosus (Centrarchidae); and Bothriocephalus morphotype from rock bass, Ambloplites rupestris (Centrarchidae). The Bothriocephalus morphotype from goldeye, Hiodon alosoides (Hiodontidae), may also represent a separate lineage (possibly Bothriocephalus texomensisSelf, 1954) but requires additional studies. A morphotype from smallmouth bass, Micropterus dolomieu, based on a single specimen, is morphologically and genetically very similar to the morphotype from rock bass. Morphological study of the scolex and strobila of heat-killed and fixed specimens has revealed consistent differences, often subtle, that allowed us to differentiate between these morphotypes.
- MeSH
- Cestoda anatomie a histologie genetika ultrastruktura MeSH
- cestodózy parazitologie veterinární MeSH
- mikroskopie elektronová rastrovací veterinární MeSH
- nemoci ryb parazitologie MeSH
- okounovití parazitologie MeSH
- Perciformes parazitologie MeSH
- pravděpodobnostní funkce MeSH
- ribozomální DNA analýza chemie MeSH
- RNA ribozomální 18S genetika MeSH
- ryby MeSH
- sekvence nukleotidů MeSH
- sekvenční seřazení veterinární MeSH
- sladká voda MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Kanada MeSH
- Spojené státy americké MeSH
Imunofenotypizace polychromatickou průtokovou cytometrií je v současné době standardem pro diagnostiku, klasifikaci a monitorování akutních leukemií. Patří k základním vyšetřovacím metodám i v diagnostice akutních obtížně klasifikovatelných leukemií. Nová revidovaná WHO klasifikace tumorů hematopoézy a lymfoidních tkání z r. 2008 rozdělila skupinu obtížně klasifikovatelných akutních leukemií na akutní nediferencovanou leukemii (AUL) a na leukemii se smíšeným fenotypem (MPAL). Cílem nově navržených kritérií je přesnější a komplexnější charakterizace onemocnění s ohledem na prognózu jednotlivých podskupin. Uvedená práce reflektuje vlastní zkušenost a současné možnosti imunologické diagnostiky u tohoto typu diagnózy.
Immunophenotyping of leukemic cells by polychromatic flow cytometry is playing an important role in the diagnosis, classification, follow-up of acute leukemias and crucial role in the management of acute leukemias of ambiguous lineage. In the revised WHO classification 2008 the former acute biphenotypic leukemia was renamed mixed phenotype acute leukemia (MPAL) and new definition criteria were established. The aim of the new classification was to simplify existing EGIL scoring system of acute biphenotypic leukemia, to assign lineage as lymphoid or myeloid if possible and to include both biphenotypic and bilineage types. The goal of this article is to approach the new aspects of immunophenotypic characterization of acute leukemias of ambiguous lineage in the context of our own experience.
- Klíčová slova
- obtížně klasifikovatelné leukemie, revidovaná WHO klasifikace 2008,
- MeSH
- akutní nemoc MeSH
- diagnostické techniky molekulární metody trendy MeSH
- imunofenotypizace trendy využití MeSH
- leukemie imunologie klasifikace MeSH
- lidé MeSH
- průtoková cytometrie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Světová zdravotnická organizace MeSH
- Check Tag
- lidé MeSH
In order to clarify the phylogenetic relationships among the main marine myxosporean clades including newly established Ceratonova clade and scrutinizing their evolutionary origins, we performed large-scale phylogenetic analysis of all myxosporean species from the marine myxosporean lineage based on three gene analyses and statistical topology tests. Furthermore, we obtained new molecular data for Ceratonova shasta, C. gasterostea, eight Ceratomyxa species and one Myxodavisia species. We described five new species: Ceratomyxa ayami n. sp., C. leatherjacketi n. sp., C. synaphobranchi n. sp., C. verudaensis n. sp. and Myxodavisia bulani n. sp.; two of these formed a new, basal Ceratomyxa subclade. We identified that the Ceratomyxa clade is basal to all other marine myxosporean lineages, and Kudoa with Enteromyxum are the most recently branching clades. Topologies were least stable at the nodes connecting the marine urinary clade, the marine gall bladder clade and the Ceratonova clade. Bayesian inference analysis of SSU rDNA and the statistical tree topology tests suggested that Ceratonova is closely related to the Enteromyxum and Kudoa clades, which represent a large group of histozoic species. A close relationship between Ceratomyxa and Ceratonova was not supported, despite their similar myxospore morphologies. Overall, the site of sporulation in the vertebrate host is a more accurate predictor of phylogenetic relationships than the morphology of the myxospore.
- MeSH
- Bayesova věta MeSH
- biologická evoluce * MeSH
- fylogeneze * MeSH
- modely genetické MeSH
- Myxozoa klasifikace MeSH
- pravděpodobnostní funkce MeSH
- ribozomální DNA genetika MeSH
- sekvenční analýza DNA MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Epigenetic variation has been proposed to contribute to the success of asexual plants, either as a contributor to phenotypic plasticity or by enabling transient adaptation via selection on transgenerationally stable, but reversible, epialleles. While recent studies in experimental plant populations have shown the potential for epigenetic mechanisms to contribute to adaptive phenotypes, it remains unknown whether heritable variation in ecologically relevant traits is at least partially epigenetically determined in natural populations. Here, we tested the hypothesis that DNA methylation variation contributes to heritable differences in flowering time within a single widespread apomictic clonal lineage of the common dandelion (Taraxacum officinale s. lat.). Apomictic clone members of the same apomictic lineage collected from different field sites showed heritable differences in flowering time, which was correlated with inherited differences in methylation-sensitive AFLP marker profiles. Differences in flowering between apomictic clone members were significantly reduced after in vivo demethylation using the DNA methyltransferase inhibitor zebularine. This synchronization of flowering times suggests that flowering time divergence within an apomictic lineage was mediated by differences in DNA methylation. While the underlying basis of the methylation polymorphism at functional flowering time-affecting loci remains to be demonstrated, our study shows that epigenetic variation contributes to heritable phenotypic divergence in ecologically relevant traits in natural plant populations. This result also suggests that epigenetic mechanisms can facilitate adaptive divergence within genetically uniform asexual lineages.
- MeSH
- analýza polymorfismu délky amplifikovaných restrikčních fragmentů MeSH
- epigeneze genetická * MeSH
- květy fyziologie MeSH
- metylace DNA * MeSH
- mikrosatelitní repetice MeSH
- nepohlavní rozmnožování MeSH
- populační genetika MeSH
- Taraxacum genetika fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Finsko MeSH
- Německo MeSH
Myxosporeans (Myxozoa) are eukaryotic parasites, primarily of fish, whose classification is in a state of flux as taxonomists attempt to synthesize the traditional morphology-based system with emerging DNA sequence-based phylogenies. The genus Sphaerospora Thélohan, 1892, which includes pathogenic species that cause significant impacts on fisheries and aquaculture, is one of the most polyphyletic taxa and exemplifies the current challenges facing myxozoan taxonomists. The type species, S. elegans, clusters within the Sphaerospora sensu stricto clade, members of which share similar tissue tropism and long insertions in their variable rRNA gene regions. However, other morphologically similar sphaerosporids lie in different branches of myxozoan phylogenetic trees. Herein, we significantly extend taxonomic sampling of sphaerosporids with SSU+LSU rDNA and EF-2 sequence data for 12 taxa including three representatives of the morphologically similar genus Polysporoplasma Sitjà-Bobadilla et Álvarez-Pellitero, 1995. These taxa were sampled from different vertebrate host groups, biogeographic realms and environments. Our phylogenetic analyses and statistical tests of single and concatenated datasets revealed Sphaerospora s. s. as a strongly supported monophyletic lineage, that clustered sister to the whole myxosporean clade (freshwater+marine lineages). Generally, Sphaerospora s. s. rDNA sequences (up to 3.7 kb) are the longest of all myxozoans and indeed metazoans. The sphaerosporid clade has two lineages, which have specific morphological, biological and sequence traits. Lineage A taxa (marine Sphaerospora spp.) have a single binucleate sporoplasm and shorter AT-rich rDNA inserts. Lineage B taxa (freshwater/brackish Sphaerospora spp.+marine/brackish Polysporoplasma spp.) have 2-12 uninucleate sporoplasms and longer GC-rich rDNA inserts. Lineage B has four subclades that correlate with host group and habitat; all Polysporoplasma species, including the type species, cluster together in one of these subclades. We thus suppress the genus Polysporoplasma and the family Polysporoplasmidae and emend the generic diagnosis of the genus Sphaerospora. The combination of morphological, biological and DNA sequence data applied in this study helped to elucidate an important part of the taxonomic puzzle within the phylum Myxozoa.
- MeSH
- biologická evoluce * MeSH
- elongační faktor 2 klasifikace genetika MeSH
- fylogeneze MeSH
- genetická variace MeSH
- malé podjednotky ribozomu genetika MeSH
- Myxozoa klasifikace genetika MeSH
- nemoci ryb parazitologie MeSH
- ribozomální DNA klasifikace genetika MeSH
- ryby parazitologie MeSH
- sekvenční analýza DNA MeSH
- velké ribozomální podjednotky genetika MeSH
- zastoupení bazí MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
