• MeSH
• genetické jevy MeSH
• typy dědičnosti genetika   MeSH
• Publikační typ
• historické články MeSH

• O autorovi
• Mendel, Johann Gregor, 1822-1884 Autorita

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

• MeSH
• anotace sekvence MeSH
• genetická predispozice k nemoci * MeSH
• genotypizační techniky MeSH
• HEK293 buňky MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 14 genetika   MeSH
• lidské chromozomy, pár 6 genetika   MeSH
• mikro RNA metabolismus   MeSH
• proliferace buněk MeSH
• reportérové geny MeSH
• reprodukovatelnost výsledků MeSH
• rizikové faktory MeSH
• rodina MeSH
• sekvence nukleotidů MeSH
• typy dědičnosti genetika   MeSH
• Waldenströmova makroglobulinemie genetika   MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Studies have suggested a role for the mammalian (or mechanistic) target of rapamycin (mTOR) in skeletal development and homeostasis, yet there is no evidence connecting mTOR with the key signaling pathways that regulate skeletogenesis. We identified a parathyroid hormone (PTH)/PTH-related peptide (PTHrP)-salt-inducible kinase 3 (SIK3)-mTOR signaling cascade essential for skeletogenesis. While investigating a new skeletal dysplasia caused by a homozygous mutation in the catalytic domain of SIK3, we observed decreased activity of mTOR complex 1 (mTORC1) and mTORC2 due to accumulation of DEPTOR, a negative regulator of both mTOR complexes. This SIK3 syndrome shared skeletal features with Jansen metaphyseal chondrodysplasia (JMC), a disorder caused by constitutive activation of the PTH/PTHrP receptor. JMC-derived chondrocytes showed reduced SIK3 activity, elevated DEPTOR, and decreased mTORC1 and mTORC2 activity, indicating a common mechanism of disease. The data demonstrate that SIK3 is an essential positive regulator of mTOR signaling that functions by triggering DEPTOR degradation in response to PTH/PTHrP signaling during skeletogenesis.

• MeSH
• HEK293 buňky MeSH
• homozygot MeSH
• intracelulární signální peptidy a proteiny metabolismus   MeSH
• lidé MeSH
• missense mutace genetika   MeSH
• mTORC1 metabolismus   MeSH
• mTORC2 metabolismus   MeSH
• mutantní proteiny chemie   metabolismus   MeSH
• osteogeneze * MeSH
• parathormon metabolismus   MeSH
• protein podobný parathormonu metabolismus   MeSH
• proteinkinasy chemie   nedostatek   genetika   metabolismus   MeSH
• proteolýza MeSH
• růstová ploténka metabolismus   MeSH
• sekvence aminokyselin MeSH
• signální transdukce * MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• typy dědičnosti genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• časná diagnóza MeSH
• dominantní geny MeSH
• geny recesivní MeSH
• hluchota genetika   MeSH
• lidé MeSH
• mitochondriální DNA genetika   MeSH
• mnohočetné abnormality epidemiologie   genetika   MeSH
• mutace MeSH
• novorozenecký screening MeSH
• poruchy sluchu * epidemiologie   genetika   vrozené   MeSH
• sekvenování celého genomu metody   MeSH
• typy dědičnosti genetika   MeSH
• Check Tag
• lidé MeSH

Chromatin is assembled by histone chaperones such as chromatin assembly factor CAF-1. We had noticed that vigor of Arabidopsis thaliana CAF-1 mutants decreased over several generations. Because changes in mutant phenotype severity over generations are unusual, we asked how repeated selfing of Arabidopsis CAF-1 mutants affects phenotype severity. CAF-1 mutant plants of various generations were grown, and developmental phenotypes, transcriptomes and DNA cytosine-methylation profiles were compared quantitatively. Shoot- and root-related growth phenotypes were progressively more affected in successive generations of CAF-1 mutants. Early and late generations of the fasciata (fas)2-4 CAF-1 mutant displayed only limited changes in gene expression, of which increasing upregulation of plant defense-related genes reflects the transgenerational phenotype aggravation. Likewise, global DNA methylation in the sequence context CHG but not CG or CHH (where H = A, T or C) changed over generations in fas2-4. Crossing early and late generation fas2-4 plants established that the maternal contribution to the phenotype severity exceeds the paternal contribution. Together, epigenetic rather than genetic mechanisms underlie the progressive developmental phenotype aggravation in the Arabidopsis CAF-1 mutants and preferred maternal transmission reveals a more efficient reprogramming of epigenetic information in the male than the female germline.

• MeSH
• alely MeSH
• Arabidopsis genetika   MeSH
• epigeneze genetická * MeSH
• fenotyp MeSH
• fyziologický stres genetika   MeSH
• genová ontologie MeSH
• metylace DNA genetika   MeSH
• mutace genetika   MeSH
• neplodnost rostlin MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• regulace genové exprese u rostlin MeSH
• sekvence nukleotidů MeSH
• semena rostlinná embryologie   MeSH
• sestřihové faktory genetika   metabolismus   MeSH
• transkriptom genetika   MeSH
• typy dědičnosti genetika   MeSH
• vajíčko rostlin embryologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The considerable genome size variation in Arabidopsis thaliana has been shown largely to be due to copy number variation (CNV) in 45S ribosomal RNA (rRNA) genes. Surprisingly, attempts to map this variation by means of genome-wide association studies (GWAS) failed to identify either of the two likely sources, namely the nucleolus organizer regions (NORs). Instead, GWAS implicated a trans-acting locus, as if rRNA gene CNV was a phenotype rather than a genotype. To explain these results, we investigated the inheritance and stability of rRNA gene copy number using the variety of genetic resources available in A. thaliana - F2 crosses, recombinant inbred lines, the multiparent advanced-generation inter-cross population, and mutation accumulation lines. Our results clearly show that rRNA gene CNV can be mapped to the NORs themselves, with both loci contributing equally to the variation. However, NOR size is unstably inherited, and dramatic copy number changes are visible already within tens of generations, which explains why it is not possible to map the NORs using GWAS. We did not find any evidence of trans-acting loci in crosses, which is also expected since changes due to such loci would take very many generations to manifest themselves. rRNA gene copy number is thus an interesting example of "missing heritability"-a trait that is heritable in pedigrees, but not in the general population.

• MeSH
• Arabidopsis genetika   MeSH
• genetické lokusy MeSH
• genová dávka MeSH
• inbreeding MeSH
• křížení genetické MeSH
• organizátor jadérka genetika   MeSH
• rekombinace genetická genetika   MeSH
• repetitivní sekvence nukleových kyselin genetika   MeSH
• RNA ribozomální genetika   MeSH
• rostlinné geny * MeSH
• typy dědičnosti genetika   MeSH
• variabilita počtu kopií segmentů DNA genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Gene targeting is becoming an important tool for precision genome engineering in plants. During gene replacement, a variant of gene targeting, transformed DNA integrates into the genome by homologous recombination (HR) to replace resident sequences. We have analysed gene targeting in barley (Hordeum vulgare) using a model system based on double-strand break (DSB) induction by the meganuclease I-SceI and a transgenic, artificial target locus. In the plants we obtained, the donor construct was inserted at the target locus by homology-directed DNA integration in at least two transformants obtained in a single experiment and was stably inherited as a single Mendelian trait. Both events were produced by one-sided integration. Our data suggest that gene replacement can be achieved in barley with a frequency suitable for routine application. The use of a codon-optimized nuclease and co-transfer of the nuclease gene together with the donor construct are probably the components important for efficient gene targeting. Such an approach, employing the recently developed synthetic nucleases/nickases that allow DSB induction at almost any sequence of a genome of interest, sets the stage for precision genome engineering as a routine tool even for important crops such as barley.

• MeSH
• dvouřetězcové zlomy DNA * MeSH
• genetické lokusy MeSH
• geneticky modifikované rostliny MeSH
• genový targeting metody   MeSH
• ječmen (rod) genetika   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• modely genetické MeSH
• reprodukovatelnost výsledků MeSH
• rostlinné geny MeSH
• transformace genetická MeSH
• typy dědičnosti genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions.

• MeSH
• Bayesova věta MeSH
• biologická evoluce * MeSH
• Chiroptera virologie   MeSH
• genom virový MeSH
• interakce hostitele a patogenu * MeSH
• mikrosatelitní repetice genetika   MeSH
• roční období MeSH
• typy dědičnosti genetika   MeSH
• virus vztekliny genetika   MeSH
• vzteklina epidemiologie   MeSH
• zeměpis MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Geografické názvy
• Peru epidemiologie   MeSH

The incidence of metabolic syndrome increases in the developed countries, therefore biomedical research is focused on the understanding of its etiology. The study of exact mechanisms is very complicated because both genetic and environmental factors contribute to this complex disease. The ability of environmental factors to promote phenotype changes by epigenetic DNA modifications (i.e. DNA methylation, histone modifications) was demonstrated to play an important role in the development and predisposition to particular symptoms of metabolic syndrome. There is no doubt that the early life, such as the fetal and perinatal periods, is critical for metabolic syndrome development and therefore critical for prevention of this disease. Moreover, these changes are visible not only in individuals exposed to environmental factors but also in the subsequent progeny for multiple generations and this phenomenon is called transgenerational inheritance. The knowledge of molecular mechanisms, by which early minor environmental stimuli modify the expression of genetic information, might be the desired key for the understanding of mechanisms leading to the change of phenotype in adulthood. This review provides a short overview of metabolic syndrome epigenetics.

• MeSH
• epigeneze genetická genetika   MeSH
• lidé MeSH
• metabolický syndrom genetika   metabolismus   MeSH
• náchylnost k nemoci metabolismus   MeSH
• typy dědičnosti genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

It is notable that the occurrence of multiple sex chromosomes differs significantly between major lineages of amniote vertebrates. In this respect, birds are especially conspicuous, as multiple sex chromosomes have not been observed in this lineage so far. On the other hand, in mammals, multiple sex chromosomes have evolved many times independently. We hypothesize that this contrast can be related to the different involvement of sex-specific sex chromosomes in female meiosis subjected to the female meiotic drive under male versus female heterogamety. Essentially, the male-specific Y chromosome is not involved in female meiosis and is therefore sheltered against the effects of the female meiotic drive affecting the X chromosome and autosomes. Conversely, the Z and W sex chromosomes are both present in female meiosis. Nonrandom segregation of these sex chromosomes as a consequence of their rearrangements connected with the emergence of multiple sex chromosomes would result in a biased sex ratio, which should be penalized by selection. Therefore, the emergence of multiple sex chromosomes should be less constrained in the lineages with male rather than female heterogamety. Our broader phylogenetic comparison across amniotes supports this prediction. We suggest that our results are consistent with the widespread occurrence of female meiotic drive in amniotes.

• MeSH
• fylogeneze MeSH
• meióza fyziologie   MeSH
• modely genetické MeSH
• plazi genetika   MeSH
• pohlavní chromozomy genetika   MeSH
• ptáci genetika   MeSH
• savci genetika   MeSH
• segregace chromozomů fyziologie   MeSH
• typy dědičnosti genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH