AIM: Estimating polymorphic allele frequencies of the NADPH-CYP450 oxidoreductase (POR) gene in a Czech Slavic population. METHODS: The POR gene was analyzed in 322 individuals from a control cohort by sequencing and high resolution melting analysis. RESULTS: We identified seven unreported SNP genetic variations, including two SNPs in the 5' flanking region (g.4965C>T and g.4994G>T), one intronic variant (c.1899-20C>T), one synonymous SNP (p.20Ala=) and three nonsynonymous SNPs (p.Thr29Ser, p.Pro384Leu and p.Thr529Met). The p.Pro384Leu variant exhibited reduced enzymatic activities compared with wild-type. CONCLUSION: New POR variant identification indicates the number of uncommon variants might be specific for each subpopulation being investigated, particularly germane to the singular role that POR plays in providing reducing equivalents to all CYP450s in the endoplasmic reticulum. Original submitted 15 September 2014; Revision submitted 17 November 2014.

• Klíčová slova
• CYP, Czech Slavic population, NADPH-cytochrome, P450 oxidoreductase, P450 reductase, POR, allele frequencies, haplotype, pharmacogenetics,
• MeSH
• DNA genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická variace MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus * MeSH
• kinetika MeSH
• kohortové studie MeSH
• konformace proteinů MeSH
• lidé MeSH
• missense mutace MeSH
• molekulární modely MeSH
• novorozenec MeSH
• sekvence nukleotidů MeSH
• substituce aminokyselin MeSH
• systém (enzymů) cytochromů P-450 chemie   genetika   metabolismus   MeSH
• vazebná nerovnováha MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• DNA MeSH
• POR protein, human MeSH Prohlížeč
• systém (enzymů) cytochromů P-450 MeSH

Genome-wide and candidate gene studies for pulmonary sarcoidosis have highlighted several candidate variants among different populations. However, the genetic basis of functional rare variants in sarcoidosis still needs to be explored. To identify functional rare variants in sarcoidosis, we sequenced exomes of 22 sarcoidosis cases from six families. Variants were prioritized using linkage and high-penetrance approaches, and filtered to identify novel and rare variants. Functional networking and pathway analysis of identified variants was performed using gene ontology based gene-phenotype, gene-gene, and protein-protein interactions. The linkage (n = 1007-7640) and high-penetrance (n = 11,432) prioritized variants were filtered to select variants with (a) reported allele frequency < 5% in databases (1.2-3.4%) or (b) novel (0.7-2.3%). Further selection based on functional properties and validation revealed a panel of 40 functional rare variants (33 from linkage region, 6 highly penetrant and 1 shared by both approaches). Functional network analysis implicated these gene variants in immune responses, such as regulation of pro-inflammatory cytokines including production of IFN-γ and anti-inflammatory cytokine IL-10, leukocyte proliferation, bacterial defence, and vesicle-mediated transport. The KEGG pathway analysis indicated inflammatory bowel disease as most relevant. This study highlights the subsets of functional rare gene variants involved in pulmonary sarcoidosis, such as, regulations of calcium ions, G-protein-coupled receptor, and immune system including retinoic acid binding. The implicated mechanisms in etiopathogenesis of familial sarcoidosis thus include Wnt signalling, inflammation mediated by chemokine and cytokine signalling and cadherin signalling pathways.

• MeSH
• celogenomová asociační studie MeSH
• exom * MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• genetická variace * MeSH
• genetické markery * MeSH
• genotyp MeSH
• genové regulační sítě * MeSH
• lidé MeSH
• plicní sarkoidóza genetika   patologie   MeSH
• rodokmen MeSH
• sekvenční analýza DNA metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• genetické markery * MeSH

We discovered that Sarcoleotia globosa (Geoglossomycetes) fruited on the soil of ornamental Erica pot cultures, and its ascospores can germinate on plain agar. These findings prompted us to collect isolates from horticultural and natural environments in Japan and analyze their phylogeny and root colonizing ability. Pure cultures were successfully obtained from ascospores and surface-sterilized ericaceous roots. Phylogenetic analysis based on rRNA internal transcribed spacer sequences revealed that Japanese samples were separated into three strongly supported clades. Individual clade consisted of samples derived from (1) Erica pot cultures, (2) Rhododendron planted in a garden or Vaccinium pot culture, and (3) natural habitats in Hokkaido. Colony characteristics and in vitro root-colonizing morphology observed may correspond to these phylogenetic variations. Irrespective of the clades, all tested strains formed hyphal coils in vital rhizodermal cells of V. virgatum seedlings, which resembled those of ericoid mycorrhizae. Our results represent novel findings that can be the first step in unraveling the currently unknown ecology of geoglossoid fungi.

• Klíčová slova
• Earth tongues, Ericoid mycorrhiza, Geoglossomycetes, Hyphal coil, In vitro re-synthesis,
• MeSH
• Ascomycota MeSH
• fylogeneze MeSH
• genetická variace MeSH
• kořeny rostlin * MeSH
• mykorhiza * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In the present work, we introduce a new type of DNA variation detection. This method represents a transfer of melting gel technique onto multicapillary electrophoresis DNA sequencing instrument with further improvements to achieve maximum sample throughput while maintaining a high performance. The main improvement comes from application of cycling (revolving) temporal temperature gradient in place of a single-sweep gradient, commonly used in similar gel-based techniques. This improvement enables utilization of multiple-injection technique, in which multiple samples are injected into the same capillary (or sets of capillaries) separated by predefined time intervals of partial electrophoresis. The periodic oscillation of the temperature results in identical separation conditions of all samples injected in such series. Using this novel approach, we demonstrate a dramatic increase in separation throughput by turning a standard commercial 96-capillary array instrument into a semicontinuous flow mutation detection system capable to screen over 15 000 samples in 24 h of operation on a single 96-capillary commercial instrument. This represents a 10-fold increase in sample throughput over the current comparable technology.

• MeSH
• časové faktory MeSH
• elektroforéza kapilární přístrojové vybavení   metody   MeSH
• genetická variace genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• mutační analýza DNA přístrojové vybavení   metody   MeSH
• polymery MeSH
• sekvenční analýza DNA přístrojové vybavení   metody   MeSH
• teplota * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• polymery MeSH

• MeSH
• antibiotická rezistence MeSH
• genetická variace * MeSH
• konjugace genetická MeSH
• mutace * MeSH
• radiační účinky MeSH
• rekombinace genetická * MeSH
• Rhizobium * účinky léků   metabolismus   účinky záření   MeSH
• streptomycin farmakologie   MeSH
• ultrafialové záření MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• streptomycin MeSH

BACKGROUND: Factor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data. METHODS: A total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR). RESULTS: Eight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters. CONCLUSIONS: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.

• Klíčová slova
• C3 glomerulonephritis (C3GN), C3 glomerulopathy, dense deposit disease (DDD), immune complex-mediated glomerulonephritis, membranoproliferative glomerulonephritis,
• MeSH
• aktivace komplementu MeSH
• alely MeSH
• biologické markery * MeSH
• dospělí MeSH
• ELISA MeSH
• genetická predispozice k nemoci MeSH
• genetická variace * MeSH
• imunokomplex imunologie   MeSH
• jednonukleotidový polymorfismus MeSH
• komplement C3 imunologie   MeSH
• komplement genetika   metabolismus   MeSH
• lidé MeSH
• management nemoci MeSH
• membranoproliferativní glomerulonefritida krev   diagnóza   etiologie   mortalita   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• náchylnost k nemoci MeSH
• prognóza MeSH
• ROC křivka MeSH
• studie případů a kontrol MeSH
• určení symptomu MeSH
• vyšetření funkce ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery * MeSH
• CFHR5 protein, human MeSH Prohlížeč
• imunokomplex MeSH
• komplement C3 MeSH
• komplement MeSH

OBJECTIVES: The term "copy number variation/variant" (CNV) denotes a DNA sequence with a magnitude of 1 kb at least which is differently represented among individuals based on its deletion or duplication. Since 2008, multiple studies have reported copy number variations in schizophrenia, and they seem to fill in a gap in our knowledge on the genetic background of schizophrenia. The aim of this review is to sum up the current findings related to CNVs in schizophrenia in order to facilitate further research. METHODS: We searched the PubMed computer database using the key words "schizophrenia AND CNVs" on 26th October 2011. Out of 91 obtained results, we selected the references based on their relevance. RESULTS: The CNVs at genome loci 1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, 16p13.1 and 22q11.2 were associated with schizophrenia most frequently. The data provide evidence for low prevalent, but highly penetrant CNVs associated with schizophrenia. CNV deletions show higher penetrance than duplications. Larger CNVs often have higher penetrance than smaller CNVs. Although the vast majority of CNVs are inherited, CNVs that have newly occurred as de novo mutations have more readily been implicated in schizophrenia. De novo CNVs may be responsible for the presence of schizophrenia in only one of the two monozygotic twins, who otherwise have identical genomes. CONCLUSION: Identifying CNVs in schizophrenia can lead to changes in the treatment and genetic counselling. Our knowledge on the genetic background of neurodevelopmental disorders may also reduce stigma in schizophrenia.

• MeSH
• celogenomová asociační studie statistika a číselné údaje   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genom lidský genetika   MeSH
• lidé MeSH
• schizofrenie genetika   MeSH
• variabilita počtu kopií segmentů DNA genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In the present study, the cDNA sequences of Hsp70 and Hsp90 genes of Isaria farinosa (designated IFHSP70 and IFHSP90) were cloned and characterized using multiple techniques of molecular biology and bioinformatics. The genetic differentiation of the two genes was investigated among 10 geographically separated populations distributed in the Yunnan province. The complete sequence of the IFHSP70 cDNA had a length of 2158 bp, and contained an open reading frame (ORF) of 1962 bp, encoding a 71-kDa polypeptide comprising of 653 amino acids. IFHSP90 cDNA had a length of 2144 bp, and contained an ORF of 2103 bp, encoding a polypeptide of 79.23 kDa, comprising of 700 amino acids. The deduced amino acid sequences of IFHSP70 and IFHSP90 shared high sequence identities with other fungi. Fundamental information pertaining to the protein families, signatures, and conserved motifs of Hsp70 and Hsp90 were also identified. Analysis of molecular variances (AMOVA) from the Hsp70 and Hsp90 genes showed that the genetic variation within-population (83.26%, 83.08%) was greater than among the populations (16.74%, 16.92%). The values of nucleotide diversity (Pi), haplotype diversity (Hd), coefficient of genetic differentiation (Fst), and gene flow (Nm) were calculated. For Hsp70, Pi = 0.0425, Hd = 0.888, Fst = 0.167, Nm = 1.24; For Hsp90, Pi = 0.0420, Hd = 0.894, Fst = 0.169, and Nm = 1.22. These data indicated that the genetic differentiation among 10 different geographical populations of I. farinosa was limited. This study describes, for the first time, cloning, characterization and identification of Isaria farinosa Hsp70 and Hsp90 genes, and provides a preliminary basis for exploring the genetic structure of the genus Isaria using the sequences of Hsp70 and Hsp90 as molecular markers.

• MeSH
• Cordyceps klasifikace   genetika   metabolismus   MeSH
• fungální proteiny chemie   genetika   metabolismus   MeSH
• fylogeneze MeSH
• genetická variace * MeSH
• otevřené čtecí rámce MeSH
• proteiny tepelného šoku HSP70 chemie   genetika   metabolismus   MeSH
• proteiny tepelného šoku HSP90 chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Čína MeSH
• Názvy látek
• fungální proteiny MeSH
• proteiny tepelného šoku HSP70 MeSH
• proteiny tepelného šoku HSP90 MeSH

BACKGROUND AND AIMS: The observed positive diversity effect on ecosystem functioning has rarely been assessed in terms of intraspecific trait variability within populations. Intraspecific phenotypic variability could stem both from underlying genetic diversity and from plasticity in response to environmental cues. The latter might derive from modifications to a plant's epigenome and potentially last multiple generations in response to previous environmental conditions. We experimentally disentangled the role of genetic diversity and diversity of parental environments on population productivity, resistance against environmental fluctuations and intraspecific phenotypic variation. METHODS: A glasshouse experiment was conducted in which different types of Arabidopsis thaliana populations were established: one population type with differing levels of genetic diversity and another type, genetically identical, but with varying diversity levels of the parental environments (parents grown in the same or different environments). The latter population type was further combined, or not, with experimental demethylation to reduce the potential epigenetic diversity produced by the diversity of parental environments. Furthermore, all populations were each grown under different environmental conditions (control, fertilization and waterlogging). Mortality, productivity and trait variability were measured in each population. KEY RESULTS: Parental environments triggered phenotypic modifications in the offspring, which translated into more functionally diverse populations when offspring from parents grown under different conditions were brought together in mixtures. In general, neither the increase in genetic diversity nor the increase in diversity of parental environments had a remarkable effect on productivity or resistance to environmental fluctuations. However, when the epigenetic variation was reduced via demethylation, mixtures were less productive than monocultures (i.e. negative net diversity effect), caused by the reduction of phenotypic differences between different parental origins. CONCLUSIONS: A diversity of environmental parental origins within a population could ameliorate the negative effect of competition between coexisting individuals by increasing intraspecific phenotypic variation. A diversity of parental environments could thus have comparable effects to genetic diversity. Disentangling the effect of genetic diversity and that of parental environments appears to be an important step in understanding the effect of intraspecific trait variability on coexistence and ecosystem functioning.

• Klíčová slova
• Arabidopsis thaliana, DNA methylation, competition, epigenetic diversity, functional traits, genetic diversity, intraspecific phenotypic variability, parental effects, productivity, transgenerational effects,
• MeSH
• Arabidopsis * genetika   MeSH
• biologická variabilita populace MeSH
• ekosystém MeSH
• fenotyp MeSH
• genetická variace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.

• MeSH
• akutní myeloidní leukemie etiologie   metabolismus   patologie   MeSH
• alely MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetická variace * MeSH
• genotyp MeSH
• hodnocení rizik MeSH
• imunita genetika   MeSH
• imunomodulace genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• náchylnost k nemoci * imunologie   MeSH
• nádorové biomarkery MeSH
• rizikové faktory MeSH
• senioři MeSH
• steroidy metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH
• steroidy MeSH