Fakt evoluce se nejčastěji opírá o paleontologická pozorování, výsledky srovnávací anatomie, znaky embryonálního vývoje a popis vestigiálních struktur, geografickou distribuci druhů a výsledky molekulárních metod. Článek dokládá fakt evoluce stručně a výběrově třemi evolučními proudy: – voda-souš na příkladu čtvernožců, – souš-voda na příkladu velryb, – země-vzduch na příkladu „opeřených dinosaurů“, a dále srovnávací anatomií korových polí savčího mozku, geografickou distribucí druhů, evolucí genomu a proteosyntézy.

Proof of evolution as a fact is most often based on paleontological observations, results of comparative anatomy, signs of embryonal development, description of vestigial structures, geographical distribution species and results of molecular methods. The paper supports evolution as a fact by three evolutionary streams: – water-land using a tetrapod example, – land-water using whales as an example, – land-air using „feathered dinosaurs“ as examples, and by comparative anatomy of cortical fields of the mammalian brain, by geographical distribution species, and by evolution of genome and proteosynthesis.

• MeSH
• alternativní sestřih MeSH
• anatomie srovnávací metody   MeSH
• genetický kód genetika   MeSH
• sestřih RNA genetika   MeSH
• vývojová biologie MeSH
• zoologie MeSH
• Publikační typ
• úvodní články MeSH

BACKGROUND: The programmed cell death 2 (Pdcd2) gene on mouse chromosome 17 was evaluated as a member of a highly conserved synteny, a candidate for an imprinted locus, and a candidate for the Hybrid sterility 1 (Hst1) gene. RESULTS: New mouse transcripts were identified at this locus: an alternative Pdcd2 mRNA skipping the last two coding exons and two classes of antisense RNAs. One class of the antisense RNA overlaps the alternative exon and the other the entire Pdcd2 gene. The antisense RNAs are alternative transcripts of the neighboring TATA-binding protein gene (Tbp) that are located mainly in the cell nucleus. Analogous alternative PDCD2 forms truncating the C-terminal domain were also detected in human and chicken. Alternative transcripts of the chicken PDCD2 and TBP genes also overlap. No correlation in the transcription of the alternative and overlapping mRNAs was detected. Allelic sequencing and transcription studies did not reveal any support for the candidacy of Pdcd2 for Hst1. No correlated expression of Pdcd2 with the other two genes of the highly conserved synteny was observed. Pdcd2, Chd1, and four other genes from this region were not imprinted in the embryo. CONCLUSION: The conservation of alternative transcription of the Pdcd2 gene in mouse, human and chicken suggests the biological importance of such truncated protein. The biological function of the alternative PDCD2 is likely to be opposite to that of the constitutive form. The ratio of the constitutive and alternative Pdcd2 mRNAs differs in the tissues, suggesting a developmental role.The identified Tbp-alternative Pdcd2-antisense transcripts may interfere with the transcription of the Pdcd2 gene, as they are transcribed at a comparable level. The conservation of the Pdcd2/Tbp sense-antisense overlap in the mouse and chicken points out its biological relevance. Our results also suggest that some cDNAs in databases labeled as noncoding are incomplete alternative cDNAs of neighboring protein-coding genes.

• MeSH
• alely MeSH
• alternativní sestřih MeSH
• apoptóza imunologie   MeSH
• exprimované sekvenční adresy MeSH
• financování organizované MeSH
• genomový imprinting MeSH
• krysa rodu rattus MeSH
• kur domácí MeSH
• lidé MeSH
• mapování chromozomů MeSH
• messenger RNA genetika   MeSH
• molekulární sekvence - údaje MeSH
• myši MeSH
• polymerázová řetězová reakce MeSH
• proteiny regulující apoptózu genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

Of 34 breeds kept in the Czech Republic 45,604 sheep were genotyped for codons 136, 154 and 171 in the prion protein gene (PRNP) during the years 2006-2014. In this cohort, haplotypes ARR, ARQ, ARH, AHQ, VRQ, AHR and ARK were detected. The haplotype AF141RQ associated with susceptibility to atypical scrapie was observed in nine out of 30 breeds analysed for this purpose. In addition, six rare nonsynonymous substitutions producing haplotypes AT137RQ, AN138RQ, AG151RQ, AH151RQ, ARL168Q and ARQE175 were identified in various breeds. Due to their low frequencies, these polymorphisms are of no potential importance for the breeding programme. With regard to their genetic particularity, Sumavka, Valachian and Cameroon breeds were screened for additional polymorphisms. Further haplotypes, AR143RQ and AS146RQ, were found in Sumavka and Cameroon, and in Valachian sheep, respectively. Frequencies of the ARR (resistance-associated), VRQ (susceptibility-associated) haplotypes, and of the most resistant ARR/ARR genotype calculated for sheep born in the years 2001-2003 and 2011-2013 documented effects of the 10 year-lasting national breeding programme. The total frequency of ARR doubled from 36.8 to 75.8 %, while the frequency of VRQ decreased from 4 to 0.7 %. The total frequency of the ARR/ARR genotype increased from 17.7 to 59 %. These data show that the national scrapie resistance breeding programme has had an important desirable effect on haplotype and genotype frequencies of PRNP in Czech sheep.

• MeSH
• chov MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• haplotypy MeSH
• ovce domácí genetika   MeSH
• polymorfismus genetický MeSH
• prionová bílkovina genetika   MeSH
• scrapie genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Alternative splicing of the proteolipid protein 1 gene (PLP1) produces two forms, PLP1 and DM20, due to alternative use of 5' splice sites with the same acceptor site in intron 3. The PLP1 form predominates in central nervous system RNA. Mutations that reduce the ratio of PLP1 to DM20, whether mutant or normal protein is formed, result in the X-linked leukodystrophy Pelizaeus-Merzbacher disease (PMD). We investigated the ability of sequences throughout PLP1 intron 3 to regulate alternative splicing using a splicing minigene construct transfected into the oligodendrocyte cell line, Oli-neu. Our data reveal that the alternative splice of PLP1 is regulated by a long-distance interaction between two highly conserved elements that are separated by 581 bases within the 1071-base intron 3. Further, our data suggest that a base-pairing secondary structure forms between these two elements, and we demonstrate that mutations of either element designed to destabilize the secondary structure decreased the PLP1/DM20 ratio, while swap mutations designed to restore the structure brought the PLP1/DM20 ratio to near normal levels. Sequence analysis of intron 3 in families with clinical symptoms of PMD who did not have coding-region mutations revealed mutations that segregated with disease in three families. We showed that these patient mutations, which potentially destabilize the secondary structure, also reduced the PLP1/DM20 ratio. This is the first report of patient mutations causing disease by disruption of a long-distance intronic interaction controlling alternative splicing. This finding has important implications for molecular diagnostics of PMD.

• MeSH
• alternativní sestřih * MeSH
• buněčné linie MeSH
• introny * MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• messenger RNA chemie   metabolismus   MeSH
• molekulární modely MeSH
• mutace MeSH
• myelinový proteolipidový protein genetika   metabolismus   MeSH
• oligodendroglie metabolismus   MeSH
• párování bází MeSH
• Pelizaeusova-Merzbacherova nemoc genetika   MeSH
• rodokmen MeSH
• sekvenční analýza DNA MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• DNA analýza   MeSH
• genetické techniky MeSH
• lékařská genetika MeSH
• lidský růstový hormon nedostatek   MeSH
• poruchy růstu genetika   MeSH
• Publikační typ
• příručky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• endokrinologie
• genetika, lékařská genetika

Motivation: Sanger sequencing is still being employed for sequence variant detection by many laboratories, especially in a clinical setting. However, chromatogram interpretation often requires manual inspection and in some cases, considerable expertise. Results: We present GLASS, a web-based Sanger sequence trace viewer, editor, aligner and variant caller, built to assist with the assessment of variations in 'curated' or user-provided genes. Critically, it produces a standardized variant output as recommended by the Human Genome Variation Society. Availability and implementation: GLASS is freely available at http://bat.infspire.org/genomepd/glass/ with source code at https://github.com/infspiredBAT/GLASS. Contact: nikos.darzentas@gmail.com or malcikova.jitka@fnbrno.cz. Supplementary information: Supplementary data are available at Bioinformatics online.

• MeSH
• alternativní sestřih MeSH
• genotypizační techniky metody   MeSH
• lidé MeSH
• nádorový supresorový protein p53 genetika   MeSH
• polymorfismus genetický MeSH
• sekvenční analýza DNA metody   MeSH
• sekvenční analýza RNA metody   MeSH
• software * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cancer is viewed as a genetic disease. According to the currently accepted model of carcinogenesis, several consequential mutations in oncogenes or tumor suppressor genes are necessary for cancer development. In this model, mutated DNA sequence is transcribed to mRNA that is finally translated into functionally aberrant protein. mRNA is viewed solely as an intermediate between DNA (with 'coding' potential) and protein (with 'executive' function). However, recent findings suggest that (m)RNA is actively regulated by a variety of processes including nonsense-mediated decay, alternative splicing, RNA editing or RNA interference. Moreover, RNA molecules can regulate a variety of cellular functions through interactions with RNA, DNA as well as protein molecules. Although, the precise contribution of RNA molecules by themselves and RNA-regulated processes on cancer development is currently unknown, recent data suggest their important role in carcinogenesis. Here, we summarize recent knowledge on RNA-related processes and discuss their potential role in cancer development.

• MeSH
• alternativní sestřih MeSH
• editace RNA MeSH
• financování organizované MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• modely genetické MeSH
• nádory genetika   patologie   MeSH
• regulace genové exprese MeSH
• RNA interference MeSH
• stabilita RNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Gastrointestinální stromální nádory (GIST) tvoří nejčastější mezenchymální nádory gastrointestinálního traktu. Velká část z nich vzniká na základě aktivačních mutací v genech KIT (75 - 85 %) nebo PDGFRA (méně než 10 %). Identifikace aktivačních mutací v genech KIT a PDGFRA, které kódují příslušné receptorové tyrozinkinázy (RTK), znamenala významný průlom v cílené terapii metastatických, neoperabilních nebo recidivujících GIST. Primární a/nebo sekundární rezistence je významným problémem biologické terapie imatinib mesylátem (IM) u pacientů s GIST. Oba typy rezistence vedou ke snížené terapeutické odpovědi na IM, případně k selhání této léčby a progresi onemocnění. Hlavním mechanizmem sekundární rezistence je vznik sekundárních mutací. Problémem progrese onemocnění je kromě primární a sekundární rezistence také selhání úplné eradikace nádorových buněk i při dlouhotrvající terapii inhibitory RTK. GIST bez přítomnosti mutací v genech KIT/PDGFRA tvoří u dospělých 10 - 15 %, u pediatrických GIST je to až 85 % případů. KIT/PDGFRA nemutované GIST tvoří heterogenní skupinu nádorů s několika molekulárně-genetickými i morfologickými odlišnostmi. Molekulárně se KIT/PDGFRA nemutované GIST liší např. mutacemi v genech BRAF, KRAS, NF1 nebo defekty v sukcinát dehydrogenázových (SDH) podjednotkách. GIST s nemutovanými geny KIT/PDGFRA vykazují nižší citlivost na cílenou terapii IM v porovnání s mutovanými GIST. Terapeutické možnosti se ve skupině KIT/PDGFRA nemutovaných GIST soustřeďují na BRAF inhibitory, inhibitory PI3K dráhy (mTOR), nebo na inhibitory receptorů IGF1R a VEGFR.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Most of them arise due to activating mutations in KIT (75 – 85 %) or PDGFRA (less than 10 %) genes. Identification of the activating mutations in KIT and PDGFRA genes, which code for receptor tyrosine kinases (RTKs), has improved the outcome of targeted therapy of metastatic, unresectable or recurrent GISTs. Primary and/or secondary resistance represents a significant problem in the targeted therapy by Imatinib mesylate (IM) in patients with GIST. An important mechanism of the secondary resistance is the evolvement of secondary mutations. Except for primary and secondary resistance, there is another problem of disease progression - a failure of tumor cells eradication even in the long term therapy of tyrosine kinase inhibitors. GISTs without mutations in KIT/PDGFRA genes constitute 10 - 15% GISTs in adults, and a majority (85 %) of pediatric GISTs. KIT/PDGFRA wild-type GISTs represent a heterogeneous group of tumors with several molecular-genetics and/or morphologic differences. KIT/PDGFRA wild-type GISTs are different in their molecular features, for example in mutations in the BRAF, KRAS, NF1 genes or defects of succinate dehydrogenase (SDH) subunits. KIT/PDGFRA wild-type GISTs are generally less sensitive to targeted therapy by tyrosine kinase inhibitors in comparison with KIT/PDGFRA mutated GISTs. Inhibitors of BRAF, PI3K (mTOR) or inhibitors of IGF1R and VEGFR receptors provide alternative therapeutic strategies.

• Klíčová slova
• IGH systém,
• MeSH
• biologická terapie MeSH
• chemorezistence * fyziologie   MeSH
• DNA analýza   MeSH
• gastrointestinální stromální tumory * etiologie   terapie   MeSH
• imatinib mesylát terapeutické užití   MeSH
• lidé MeSH
• mutace genetika   MeSH
• protinádorové látky MeSH
• protoonkogenní proteiny B-raf antagonisté a inhibitory   fyziologie   terapeutické užití   MeSH
• receptor IGF typ 1 fyziologie   MeSH
• sukcinátdehydrogenasa fyziologie   MeSH
• tyrosinkinasy antagonisté a inhibitory   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Telomerase is essential for proper functioning of telomeres in eukaryotes. We cloned and characterised genes for the protein subunit of telomerase (TERT) in the allotetraploid Nicotiana tabacum (tobacco) and its diploid progenitor species Nicotiana sylvestris and Nicotiana tomentosiformis with the aim of determining if allopolyploidy (hybridisation and genome duplication) influences TERT activity and divergence. Two of the three sequence variants present in the tobacco genome (NtTERT-C/s and NtTERT-D) revealed similarity to two sequence variants found in N. sylvestris and another variant (NtTERT-C/t) was similar to TERT of N. tomentosiformis. Variants of N. sylvestris origin showed less similarity to each other (80.5 % in the genomic region; 90.1 % in the coding sequence) than that between the NtTERT-C/s and NtTERT-C/t variants (93.6 and 97.2 %, respectively). The NtTERT-D variant was truncated at the 5' end, and indels indicated that it was a pseudogene. All tobacco variants were transcribed and alternatively spliced sequences were detected. Analysis of gene arrangements uncovered a novel exon in the N-terminal domain of TERT variants, a feature that is likely to be commonly found in Solanaceae species. In addition, species-specific duplications were observed within exon 5. The putative function, copy number and evolutionary origin of these NtTERT sequence variants are discussed.

• MeSH
• alternativní sestřih MeSH
• exony MeSH
• genetická transkripce MeSH
• genetické lokusy MeSH
• genom rostlinný MeSH
• genová přestavba MeSH
• introny MeSH
• izoformy RNA MeSH
• molekulární evoluce MeSH
• molekulární sekvence - údaje MeSH
• pořadí genů MeSH
• pseudogeny MeSH
• repetitivní sekvence nukleových kyselin MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• tabák genetika   MeSH
• telomerasa genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Biallelic pathogenic GJB2 gene mutations cause pre-lingual genetic hearing loss in up to 50% of individuals with bilateral sensorineural hearing loss worldwide. Sequencing of the entire GJB2 gene-coding region in Czech patients with pre-lingual bilateral hearing loss revealed that 10.3% of Czech patients carry only one monoallelic pathogenic mutation in the coding region of the GJB2 gene, which is significantly more than the population frequency of 3.4%. The 309-kb GJB6 deletion, frequent in Spain and France, is very rare in the Czech population. In order to evaluate the impact of the IVS1 + 1 G to A splice site mutation in the non-coding part of the GJB2 gene among Czech patients, we tested all available patients with pre-lingual hearing loss with only one monoallelic mutation in the coding part of GJB2. By sequencing of the exon 1 region of the GJB2 gene and HphI restriction analysis in 20 Czech patients we identified nine patients carrying IVS1 + 1 G to A. Testing for this mutation explained deafness in 45% of Czech GJB2 monoallelic patients. This mutation represents now 4% of GJB2 pathogenic mutations in Czech patients and is the third most common GJB2 mutation found in our cohort of 242 unrelated Czech patients with prelingual hearing loss. A similar frequency may also be expected in other Central European or Slavic populations.

• MeSH
• alely MeSH
• financování organizované MeSH
• genetické testování MeSH
• kohortové studie MeSH
• konexiny genetika   MeSH
• lidé MeSH
• místa sestřihu RNA genetika   MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• oboustranná nedoslýchavost diagnóza   epidemiologie   genetika   MeSH
• restrikční mapování MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH