Genomický imprinting je jedním z epigenetických faktorů, které ovlivňují genové exprese. V užším (exaktně badatelském) slova smyslu představuje genomický imprinting fáze aktivity a inaktivity určitých genů, a to nejen v různých obdobích ontogeneze, ale dokonce i v různých tkáních téhož jedince ve stejném čase. Identický gen pak exprimuje různě a klinické projevy jsou velmi variabilní. V širším (klinickém) významu je zdůrazňována závislost aktivace genu na jeho rodičovském původu. Genomický imprinting se projeví jako výjimka z 3. Mendelova zákona, neboť závažnost klinické manifestace některých autozomálních mutací je závislá na pohlaví rodiče, od kterého je mutace děděna. V minulém století byla rozpoznána velká a různorodá skupina genetických syndromů a chorob, jejichž klinické projevy se liší v závislosti na rodičovském původu odpovědné mutace, jako jsou Albrightova hereditární osteodysplazie, progresivní oseální hyperplazie, Curschmannova-Steinertova dystrofická myotonie, Huntingtonova chorea, Beckwith-Wiedemannův EMG, Silver-Russellův, Angelmanův, Prader-Williho syndrom. Genomický imprinting přispívá k objasnění variabilní expresivity, neúplné penetrance, generační anticipace aj.

Genomic imprinting is one of epigenetic factors, which influences expression of genes. It represents specific marking of some chromosome segments depending on the parental origin of the mutation. Imprinted genes are for some time inactive; such period varies in different developmental stage and in different tissues. Such inactivation is manifested as expriming genes and represents an exception to the 3rd Mendel’s rule. In the last 10 years, a large group of disorders was recognised, the clinical manifestation of which depends on the parental origin of the mutation, such as Albright’s hereditary osteodystrophy, progressive osseous hyperplasia, Curschmann-Steinert myotonic dystrophy, Huntington disease, Beckwith-Wiedemann EMG syndrome, Silver-Russell syndrome, Angelman syndrome, Prader-Willi syndrome. Genomic imprinting contributes to the clarification of mechanisms of the variable expressivity, incomplete penetration, generation anticipation etc.

• MeSH
• Angelmanův syndrom etiologie   genetika   MeSH
• Beckwithův-Wiedemannův syndrom diagnóza   etiologie   genetika   MeSH
• finanční podpora výzkumu jako téma MeSH
• genomový imprinting MeSH
• lidé MeSH
• mutace MeSH
• Praderův-Williho syndrom etiologie   genetika   MeSH
• syndrom fragilního X genetika   MeSH
• syndrom diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

Ťahyňa virus (TAHV), a member of the Bunyaviridae family (California complex), is an important but neglected human mosquito-borne pathogen. The virus genome is composed of three segments, i.e., small (S), medium (M), and large (L). Previous studies on genetic variability of viruses within the California complex were focused on S and M segments, but the L segment remains relatively unstudied. To assess the genetic variation and the relation to virus phenotype we analyzed the L segment sequences of biologically diverse TAHV strains isolated in the Czech Republic and Slovakia. Phylogenetic analysis covering all available sequences of the L segment of TAHV clearly revealed two distinguished lineages, tentatively named as "European" and "Asian". The L segment strains within the European lineage are highly conserved (identity 99.3%), whilst Asian strains are more genetically diverse (identity 97%). Based on sequence comparison with other bunyaviruses, several non-synonymous nucleotide substitutions unique for TAHV in the L segment were identified. We also identified specific residue substitutions in the endonuclease domain of TAHV compared with the La Crosse virus. Since the endonuclease domain of the La Crosse virus has been resolved, we employed an all energy landscape algorithm to analyze the ligand migration of a viral polymerase inhibitor. This allowed us to demonstrate, at the atomic level, that this viral polymerase inhibitor randomly explored the specific residue substitutions in the endonuclease domain of the TAHV L segment.

• MeSH
• antivirové látky farmakologie   MeSH
• fylogeneze MeSH
• genetická variace MeSH
• genom virový genetika   MeSH
• genotyp MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• RNA virová genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• sekvenční seřazení MeSH
• virová léková rezistence genetika   MeSH
• virové proteiny genetika   MeSH
• viry kalifornské encefalitidy účinky léků   genetika   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Following the discovery in 1998 of -H2AX, the first histone modification induced by DNA damage, interest in the changes to chromatin induced by DNA damage has exploded, and a vast amount of information has been generated. However, there has been a discrepancy between our rapidly advancing knowledge of how chromatin responds to DNA damage and the understanding of why cells mobilize large segments of chromatin to protect the genome against destabilizing effects posed by tiny DNA lesions. Recent research has provided insights into these issues and suggests that chromatin responses induced by DNA damage are not simply the accumulation of 'nuclear foci' but are mechanisms required to guard genome integrity.

• MeSH
• buněčný cyklus * genetika   MeSH
• histony * metabolismus   MeSH
• lidé MeSH
• nestabilita genomu * MeSH
• oprava DNA MeSH
• poškození DNA * MeSH
• posttranslační úpravy proteinů MeSH
• restrukturace chromatinu * genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

Hantaviruses, well-known human pathogens, have only recently been identified on the African continent. Tigray virus (TIGV) was found in Ethiopia in 2012 in a Murinae species, Stenocephalemys albipes, but the genetic data obtained at that time were too limited to correctly assess its phylogenetic position within the hantavirus tree. We used high throughput sequencing to determine the complete genome of TIGV, which showed a typical hantavirus organisation. The large (L), medium (M), and small (S) genome segments were found to be 6532, 3594 and 1908 nucleotides long, respectively, and the 5' and 3' termini for all three segments were predicted to form the panhandle-like structure typical for bunyaviruses. Nucleotide-based phylogenetic analyses revealed that all three coding segments cluster in the phylogroup III sensu Guo et al. (2013). However, while TIGV S segment is basal to the Murinae-associated hantaviruses, the M and L segments are basal to the Soricomorpha-associated hantaviruses. TIGV is the first Murinae-borne hantavirus showing this inconsistent segmental clustering in the hantavirus phylogenetic tree. We finally propose non-exclusive scenarios that could explain the original phylogenetic position of TIGV.

• MeSH
• genom virový genetika   MeSH
• genomika MeSH
• hantavirové infekce veterinární   virologie   MeSH
• Hantavirus genetika   MeSH
• Murinae virologie   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Etiopie MeSH

Uropathogenic Escherichia coli (UPEC) isolates contain large genomic segments, termed pathogenicity islands (PAIs), that contribute to their virulence. A total of 150 UPEC and 50 commensal E. coli isolates from outpatients were investigated for antimicrobial susceptibility and the presence of eight PAI markers. One hundred ninety (95 %) isolates were resistant to one or more antimicrobial agents. The most frequent resistance found against amoxicillin (68 %), amoxicillin/clavulanic acid (55 %), aztreonam (50 %), trimethoprim/sulfamethoxazole (46 %) and tetracycline (43.5 %). Antimicrobial resistance among UPEC isolates was higher than that of commensals. PAI markers were detected in substantial percentage of commensal (88 %) and UPEC isolates (98.6 %) (P > 0.05). The most prevalent PAI marker among UPEC and commensal isolates was PAI IV536 (98.7 % UPEC vs. 84 % commensal). We found a high number of PAI markers such as PAI ICFT073, PAI IICFT073, PAI I536, PAI II536, PAI III536 and PAI IIJ96 significantly associated with UPEC. PAI III536 (21.3 %) and PAI IIJ96 (8 %) were detected only in the uropathogenic isolates. Several different combinations of PAIs were found among UPEC isolates. Comparison of PAIs among UPEC and commensal isolates showed that many UPEC isolates (79.3 %) carried two or more PAI markers, while 6 % of commensals had two PAI markers (P < 0.05). The most frequent combinations of PAI markers in UPEC isolates were PAI IV536 + PAI IICFT073 (18 %) and PAI IV536 + PAI ICFT073 + PAI IICFT073 (18 %). These results indicate that PAI markers are widespread among commensal and UPEC isolates and these commensal isolates may be reservoirs for transmission of these markers.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence MeSH
• genetické markery * MeSH
• genom bakteriální * MeSH
• genomové ostrovy * MeSH
• infekce vyvolané Escherichia coli mikrobiologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• studie případů a kontrol MeSH
• symbióza MeSH
• uropatogenní Escherichia coli účinky léků   genetika   patogenita   MeSH
• virulence genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Missing heritability in human diseases represents a major challenge, and this is particularly true for ABCA4-associated Stargardt disease (STGD1). We aimed to elucidate the genomic and transcriptomic variation in 1054 unsolved STGD and STGD-like probands. METHODS: Sequencing of the complete 128-kb ABCA4 gene was performed using single-molecule molecular inversion probes (smMIPs), based on a semiautomated and cost-effective method. Structural variants (SVs) were identified using relative read coverage analyses and putative splice defects were studied using in vitro assays. RESULTS: In 448 biallelic probands 14 known and 13 novel deep-intronic variants were found, resulting in pseudoexon (PE) insertions or exon elongations in 105 alleles. Intriguingly, intron 13 variants c.1938-621G>A and c.1938-514G>A resulted in dual PE insertions consisting of the same upstream, but different downstream PEs. The intron 44 variant c.6148-84A>T resulted in two PE insertions and flanking exon deletions. Eleven distinct large deletions were found, two of which contained small inverted segments. Uniparental isodisomy of chromosome 1 was identified in one proband. CONCLUSION: Deep sequencing of ABCA4 and midigene-based splice assays allowed the identification of SVs and causal deep-intronic variants in 25% of biallelic STGD1 cases, which represents a model study that can be applied to other inherited diseases.

• MeSH
• ABC transportéry genetika   MeSH
• genomika MeSH
• introny MeSH
• lidé MeSH
• makulární degenerace * genetika   MeSH
• mutace MeSH
• rodokmen MeSH
• Stargardtova nemoc MeSH
• transkriptom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Acipenseriformes is a basal lineage of ray-finned fishes and comprise 27 extant species of sturgeons and paddlefishes. They are characterized by several specific genomic features as broad ploidy variation, high chromosome numbers, presence of numerous microchromosomes and propensity to interspecific hybridization. The presumed palaeotetraploidy of the American paddlefish was recently validated by molecular phylogeny and Hox genes analyses. A whole genome duplication in the paddlefish lineage was estimated at approximately 42 Mya and was found to be independent from several genome duplications evidenced in its sister lineage, i.e. sturgeons. We tested the ploidy status of available chromosomal markers after the expected rediploidization. Further we tested, whether paralogs of Hox gene clusters originated from this paddlefish specific genome duplication are cytogenetically distinguishable. RESULTS: We found that both paralogs HoxA alpha and beta were distinguishable without any overlapping of the hybridization signal - each on one pair of large metacentric chromosomes. Of the HoxD, only the beta paralog was unequivocally identified, whereas the alpha paralog did not work and yielded only an inconclusive diffuse signal. Chromosomal markers on three diverse ploidy levels reflecting different stages of rediploidization were identified: quadruplets retaining their ancestral tetraploid condition, semi-quadruplets still reflecting the ancestral tetraploidy with clear signs of advanced rediploidization, doublets were diploidized with ancestral tetraploidy already blurred. Also some of the available microsatellite data exhibited diploid allelic band patterns at their loci whereas another locus showed more than two alleles. CONCLUSIONS: Our exhaustive staining of paddlefish chromosomes combined with cytogenetic mapping of ribosomal genes and Hox paralogs and with microsatellite data, brings a closer look at results of the process of rediploidization in the course of paddlefish genome evolution. We show a partial rediploidization represented by a complex mosaic structure comparable with segmental paleotetraploidy revealed in sturgeons (Acipenseridae). Sturgeons and paddlefishes with their high propensity for whole genome duplication thus offer suitable animal model systems to further explore evolutionary processes that were shaping the early evolution of all vertebrates.

• MeSH
• diploidie * MeSH
• duplikace genu * MeSH
• genomika * MeSH
• genotypizační techniky MeSH
• hybridizace in situ fluorescenční * MeSH
• mikrosatelitní repetice genetika   MeSH
• ribozomy genetika   MeSH
• rybí proteiny genetika   MeSH
• ryby genetika   MeSH
• sekvenční homologie nukleových kyselin * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• cytogenetika * MeSH
• genomika * MeSH
• Publikační typ
• terminologické slovníky MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• genetika, lékařská genetika

Labeling of oligonucleotide reporter probes (RP) with electroactive markers has frequently been utilized in electrochemical detection of DNA hybridization. Osmium tetroxide complexes with tertiary amines (Os,L) bind covalently to pyrimidine (predominantly thymine) bases in DNA, forming stable, electrochemically active adducts. We propose a technique of electrochemical "multicolor" DNA coding based on RP labeling with Os,L markers involving different nitrogenous ligands (such as 2,2' -bipyridine, 1,10-phenanthroline derivatives or N,N,N',N'-tetramethylethylenediamine). At carbon electrodes the Os,L-labeled RPs produce specific signals, with the potentials of these differing depending on the ligand type. When using Os,L markers providing sufficiently large differences in their peak potentials, parallel analysis of multiple target DNA sequences can easily be performed via DNA hybridization at magnetic beads followed by voltammetric detection at carbon electrodes. Os,L labeling of oligonucleotide probes comprising a segment complementary to target DNA and an oligo(T) tail (to be modified with the osmium complex) does not require any organic chemistry facilities and can be achieved in any molecular biological laboratory. We also for the first time show that this technology can be used for labeling of oligonucleotide probes hybridizing with target DNAs that contain both purine and pyrimidine bases.

• MeSH
• barva MeSH
• DNA sondy MeSH
• elektrochemie MeSH
• elektrody MeSH
• financování organizované MeSH
• hybridizace nukleových kyselin MeSH
• oxid osmičelý MeSH

Mastomys natalensis is a rodent of African origin afflicted with a very high incidence of skin tumors (keratoacanthomas and squamous carcinomas), which are associated with a papillomavirus, M. natalensis papillomavirus (MnPV). We have determined the genomic sequence of MnPV, which has a size of 7687 bp. The genomic organization is similar to that of other papillomaviruses, with open reading frames E6, E7, E1, E2, and E4 in the early and L2 and L1 in the late region. Due to an unusually large hinge region, the transcriptional activator E2 has a size of 542 amino acids rather than 400 to 460 amino acids, as in other papillomaviruses. An open reading frame E5 coding for a small hydrophobic membrane protein is missing, as is the case for some cutaneous human papillomaviruses (HPV). This fact, together with the composition of cis-responsive elements in its long control region and phylogenetic evaluation of segments of its E6, E1, and L1 genes, indicates a relationship of MnPV to the cottontail rabbit papillomavirus and several HPV types found in lesions of cutaneous epithelia, in particular to those that are associated with epidermodysplasia verruciformis. MnPV may be a useful model system for tumorigenesis of cutaneous epithelia in humans.

• MeSH
• genom virový * MeSH
• keratoakantom virologie   MeSH
• klonování DNA MeSH
• molekulární sekvence - údaje MeSH
• Muridae * virologie   MeSH
• nádory kůže virologie   MeSH
• otevřené čtecí rámce MeSH
• Papillomaviridae * genetika   klasifikace   MeSH
• regulační oblasti nukleových kyselin genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• sekvenční homologie nukleových kyselin MeSH
• sekvenční seřazení MeSH
• spinocelulární karcinom virologie   MeSH
• virové geny * MeSH
• virové proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH