gene fragmentation
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Východisko. Rettův syndrom je onemocnění, které se projevuje poruchou psychomotorického vývoje dítěte a které se manifestuje téměř výlučně u dívek. Dědičnost onemocnění je gonozomálně dominantní s výskytem přibližně 1 na 10 000–15 000 děvčat. Molekulární podstatou onemocnění jsou mutace v genu pro metyl-CpG vážící protein 2, označovaném MeCP 2. Tento protein má významnou úlohu v komplikovaném systému regulace genové exprese. V genu pro metyl-CpG vážící protein 2 bylo u dívek s Rettovým syndromem popsáno 5 častých mutací v jeho třetím exonu. Čtyři z nich lze určit pomocí restrikčního štěpení. Cílem předkládané práce bylo studium výskytu těchto čtyř mutací ve skupině 22 českých a slovenských dívek s klinickou diagnózou Rettova syndromu. Metody a výsledky. Bylo vyšetřeno 22 dívek s Rettovým syndromem. V genu pro mety-CpG vážící protein 2 byly pomocí restrikční analýzy nalezeny 3 ze 4 hledaných mutací (T158M, R168X, R270X) u 6 postižených dívek (27 %). Mutace byly následně potvrzeny přímým sekvenováním v obou směrech. Mutace R306C, která je častá u švédských a anglických nemocných, nebyla v našem souboru nalezena. Závěry. Diagnostika Rettova syndromu i genetické poradenství v postižených rodinách by měly vycházet z úzké spolupráce pediatrických, neurologických a genetických pracovišť se specializovanými laboratořemi, které se zabývají molekulárně biologickou diagnostikou.
Background. Rett syndrome is an X-linked dominant neurodevelopmental disorder affecting 1 from 10,000 to 15,000 females worldwide. The responsible gene, encoding methyl-CpG binding protein 2 was recently identified. Methyl-CpG binding protein 2 is thought to act as a global transcriptional repressor. In the methyl-CpG binding protein 2 gene are known 5 prevalent mutations that cause Rett syndrome. Four of them are detectable by restriction analysis. In this study we present the results of the molecular study of four prevalent mutations in the gene for methyl-CpG binding protein 2 in Czech and Slovak patients with Rett syndrome. Methods and Results. 22 females with Rett syndrome were investigated by methods of molecular biology. Restriction analysis and direct sequencing of PCR products revealed in methyl-CpG binding protein 2 gene 3 different mutations (T158M, R168X, R270X) in six unrelated patients with Rett syndrome. Mutation R306C, frequent in Great Britain and Sweeden, was not detected in our group of patients with Rett syndrome. Conclusions. The diagnosis of Rett syndrome and genetic counselling in affected families should go out from the close cooperation of the pediatric, neurologic, and genetic departments with the specialized laboratories dealing with the molecular biological diagnosis.
Diplonemids are highly abundant heterotrophic marine protists. Previous studies showed that their strikingly bloated mitochondrial genome is unique because of systematic gene fragmentation and manifold RNA editing. Here we report a comparative study of mitochondrial genome architecture, gene structure and RNA editing of six recently isolated, phylogenetically diverse diplonemid species. Mitochondrial gene fragmentation and modes of RNA editing, which include cytidine-to-uridine (C-to-U) and adenosine-to-inosine (A-to-I) substitutions and 3' uridine additions (U-appendage), are conserved across diplonemids. Yet as we show here, all these features have been pushed to their extremes in the Hemistasiidae lineage. For example, Namystynia karyoxenos has its genes fragmented into more than twice as many modules than other diplonemids, with modules as short as four nucleotides. Furthermore, we detected in this group multiple A-appendage and guanosine-to-adenosine (G-to-A) substitution editing events not observed before in diplonemids and found very rarely elsewhere. With >1,000 sites, C-to-U and A-to-I editing in Namystynia is nearly 10 times more frequent than in other diplonemids. The editing density of 12% in coding regions makes Namystynia's the most extensively edited transcriptome described so far. Diplonemid mitochondrial genome architecture, gene structure and post-transcriptional processes display such high complexity that they challenge all other currently known systems.
Phylum Euglenozoa comprises three groups of eukaryotic microbes (kinetoplastids, diplonemids, and euglenids), the mitochondrial (mt) genomes of which exhibit radically different modes of organization and expression. Gene fragmentation is a striking feature of both euglenid and diplonemid mtDNAs. To rationalize the emergence of these highly divergent mtDNA types and the existence of insertion/deletion RNA editing (in kinetoplastids) and trans-splicing (in diplonemids), we propose that in the mitochondrion of the common evolutionary ancestor of Euglenozoa, small expressed gene fragments promoted a rampant neutral evolutionary pathway. Interactions between small antisense transcripts of these gene fragments and full-length transcripts, assisted by RNA-processing enzymes, permitted the emergence of RNA editing and/or trans-splicing activities, allowing the system to tolerate indel mutations and further gene fragmentation, respectively, and leading to accumulation of additional mutations. In this way, dramatically different mitochondrial genome structures and RNA-processing machineries were able to evolve. The paradigm of constructive neutral evolution acting on the widely different mitochondrial genetic systems in Euglenozoa posits the accretion of initially neutral molecular interactions by genetic drift, leading inevitably to the observed 'irremediable complexity'.
Booklice in the genus Liposcelis (Psocodea: Liposcelididae) are essential storage pests worldwide. Fragmented mt genomes have been identified in the Liposcelis species together with the typical mitochondrial (mt) genome, which is a single circular chromosome with 37 genes. Gene rearrangement, pseudogenes, and repeat regions (RRs) are very common among fragmented mt genomes. We sequenced the mt genome of the booklouse L. brunnea, the type species of the genus Liposcelis. We identified 37 genes in the mt genome of L. brunnea, which was fragmented into three chromosomes. The chromosomes I, II, III were 7.3 kb, 5.5 kb, and 5.3 kb in size with 9, 19, and 15 genes, respectively. In addition, 16 pseudogenes and four repeat regions were present in three chromosomes. Gene rearrangement in the mt genome of L. brunnea was obvious compared to that in other mt genomes in the genus Liposcelis. We found a possible correlation among mt genome rearrangement, the morphological classification standard, and phylogenetic relationships. In summary, a three-chromosome mt genome in an insect was identified for the first time, which may aid in understanding mt genome fragmentation, gene rearrangement, and evolution.
- MeSH
- fylogeneze MeSH
- genom mitochondriální genetika MeSH
- hmyz genetika MeSH
- hmyzí geny genetika MeSH
- molekulární evoluce MeSH
- multigenová rodina genetika MeSH
- pořadí genů MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Using two primer pairs constructed in silico for the amplification of the intervening sequences (IVSs) of the 23S rRNA gene sequences of the genus Taylorella, none of the three representative T. equigenitalis strains NCTC11184(T), Kentucky 188 and EQ59 was shown to contain any IVSs in the first quarter region. In the central region, all three strains possessed one approximately 70 bp IVS (TeIVS2) different from any IVSs found in T. asinigenitalis. The predicted secondary structure model of the IVSs contained stem and loop structures. The central region of the IVS-stem structure contains an identical double-stranded consensus 15-bp sequence. The purified RNA fraction from the three strains contained 16S and 4-5S RNA species but no 23S rRNA species. Thus, the primary 23S rRNA transcripts from the three strains would be cleaved into approximately 1.2- and 1.6-kb rRNA fragments and approximately 70-bp IVS. In addition, 16 other T. equigenitalis isolates were found to carry a similar 70-bp IVS in the central region and to produce fragmented 23S rRNA.
- MeSH
- bakteriální geny MeSH
- bakteriální RNA genetika MeSH
- druhová specificita MeSH
- gramnegativní bakteriální infekce mikrobiologie veterinární MeSH
- introny genetika MeSH
- koně MeSH
- konformace nukleové kyseliny MeSH
- konsenzuální sekvence MeSH
- molekulární sekvence - údaje MeSH
- nemoci koní mikrobiologie MeSH
- posttranskripční úpravy RNA MeSH
- RNA ribozomální 23S genetika MeSH
- sekvence nukleotidů MeSH
- sekvenční homologie nukleových kyselin MeSH
- sekvenční seřazení MeSH
- Taylorella equigenitalis genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
V minulých letech bylo publikováno mnoho rozporuplných studií týkajících se souvislosti mezi inzerčně-delečním polymorfizmem a renálními a kardiovaskulárními onemocněními. Většina studií podporuje vztah mezi homozygoty pro deleční alelu (DD polymorfizmus) a progresivnějším průběhem některých renálních onemocnění (především IgA nefropatie a diabetické nefropatie). Dále je pravděpodobný vztah mezi nositeli deleční alely a orgánovým poškozením u hypertoniků. Existuje i určitý vztah mezi inzerčně delečním polymorfizmem a terapeutickou odpovědí na inhibitory angiotenzinkonvertujícího enzymu, pravděpodobně v závislosti na pohlaví. Zatím neexistují jednoznač- né vztahy mezi inzerčně delečním polymorfizmem a určitými patofyziologickými mechanizmy.
Many controversial studies concerning relation between angiotensin converting enzyme polymorphism and renal and cardiovascular disease have been published during the last years. Most of the papers have suggested that the DD genotype plays an important negative role in the progression of some renal diseases (e.g. IgA nephropathy, diabetic nepropathy). The D allele may be an independent risk factor for development of the target organ damage in essential hypertension. The therapeutic response on inhibitors of angiotensin converting enzyme depends on insertion-deletion polymorphism. It probably also depends on the gender. The pathological mechanisms of insertion-deletion polymor- phism have not yet been clearly identified.
