Feline coronavirus (FCoV) is a complex pathogen causing feline infectious peritonitis (FIP). Host genetics represents a factor contributing to the pathogenesis of the disease. Differential susceptibility of various breeds to FIP was reported with controversial results. The objective of this study was to compare the genetic diversity of different breeds on a panel of candidate genes potentially affecting FCoV infection. One hundred thirteen cats of six breeds were genotyped on a panel of sixteen candidate genes. SNP allelic/haplotype frequencies were calculated; pairwise FST and molecular variance analyses were performed. Principal coordinate (PCoA) and STRUCTURE analyses were used to infer population structure. Interbreed differences in allele frequencies were observed. PCoA analysis performed for all genes of the panel indicated no population substructure. In contrast to the full marker set, PCoA of SNP markers associated with FCoV shedding (NCR1 and SLX4IP) showed three clusters containing only alleles associated with susceptibility to FCoV shedding, homozygotes and heterozygotes for the susceptibility alleles, and all three genotypes, respectively. Each cluster contained cats of multiple breeds. Three clusters of haplotypes were identified by PCoA, two clusters by STRUCTURE. Haplotypes of a single gene (SNX5) differed significantly between the PCoA clusters.

• Klíčová slova
• SNP, candidate genes, feline coronavirus (FCoV), interbreed differences, principal coordinate analysis (PCoA),
• Publikační typ
• časopisecké články MeSH

In Saccharomyces cerevisiae, the Yap family of basic leucine zipper (bZip) proteins contains eight members. The Yap family proteins are implicated in a variety of stress responses; among these proteins, Yap1 acts as a major regulator of oxidative stress responses. However, the functional roles of the remaining Yap family members are poorly understood. To elucidate the function of Yap2, we mined candidate target genes of Yap2 by proteomic analysis. Among the identified genes, FRM2 was previously identified as a target gene of Yap2, which confirmed the validity of our screening method. YNL134C and YDL124W were also identified as candidate Yap2 target genes. These genes were upregulated in strains overexpressing Yap2 and possess Yap2 target sequences in their promoter regions. Furthermore, chromatin immunoprecipitation assays showed that YNL134C and YDL124W have Yap2 binding motif. These data will help to elucidate the functional role of Yap2.

• MeSH
• alkoholoxidoreduktasy biosyntéza   genetika   MeSH
• chromatinová imunoprecipitace MeSH
• DNA fungální genetika   MeSH
• geny hub * MeSH
• oxidoreduktasy biosyntéza   genetika   MeSH
• promotorové oblasti (genetika) MeSH
• proteomika metody   MeSH
• regulace genové exprese u hub * MeSH
• Saccharomyces cerevisiae - proteiny biosyntéza   genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkoholoxidoreduktasy MeSH
• CAD1 protein, S cerevisiae MeSH Prohlížeč
• DNA fungální MeSH
• oxidoreduktasy MeSH
• Saccharomyces cerevisiae - proteiny MeSH
• transkripční faktory MeSH
• YDL124W protein, S cerevisiae MeSH Prohlížeč
• YNL134C protein, S cerevisiae MeSH Prohlížeč

Transdifferentiation of fibroblasts into induced neuronal cells (iNs) by the neuron-specific transcription factors Brn2, Myt1l, and Ascl1 is a paradigmatic example of inter-lineage conversion across epigenetically distant cells. Despite tremendous progress regarding the transcriptional hierarchy underlying transdifferentiation, the enablers of the concomitant epigenome resetting remain to be elucidated. Here, we investigated the role of KMT2A and KMT2B, two histone H3 lysine 4 methylases with cardinal roles in development, through individual and combined inactivation. We found that Kmt2b, whose human homolog's mutations cause dystonia, is selectively required for iN conversion through suppression of the alternative myocyte program and induction of neuronal maturation genes. The identification of KMT2B-vulnerable targets allowed us, in turn, to expose, in a cohort of 225 patients, 45 unique variants in 39 KMT2B targets, which represent promising candidates to dissect the molecular bases of dystonia.

• Klíčová slova
• KMT2B, MLL2, cell fate conversion, dystonia, epigenetics, histone H3 lysine 4 methylation, induced neuronal cells, mouse embryonic fibroblasts, myocytes, transdifferentiation,
• MeSH
• buněčná diferenciace genetika   MeSH
• dystonie genetika   MeSH
• embryo savčí cytologie   MeSH
• epigeneze genetická MeSH
• fibroblasty cytologie   MeSH
• genetické asociační studie * MeSH
• histonlysin-N-methyltransferasa metabolismus   MeSH
• histony metabolismus   MeSH
• lidé MeSH
• lysin metabolismus   MeSH
• metylace MeSH
• myši knockoutované MeSH
• neurony metabolismus   patologie   MeSH
• protoonkogenní protein MLL metabolismus   MeSH
• transdiferenciace buněk * genetika   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• histony MeSH
• Kmt2a protein, mouse MeSH Prohlížeč
• KMT2B protein, human MeSH Prohlížeč
• Kmt2d protein, mouse MeSH Prohlížeč
• lysin MeSH
• protoonkogenní protein MLL MeSH

Hybrid sterility is a common first step in the evolution of postzygotic reproductive isolation. According to Haldane's Rule, it affects predominantly the heterogametic sex. While the genetic basis of hybrid male sterility in organisms with heterogametic males has been studied for decades, the genetic basis of hybrid female sterility in organisms with heterogametic females has received much less attention. We investigated the genetic basis of reproductive isolation in two closely related avian species, the common nightingale (Luscinia megarhynchos) and the thrush nightingale (L. luscinia), that hybridize in a secondary contact zone and produce viable hybrid progeny. In accordance with Haldane's Rule, hybrid females are sterile, while hybrid males are fertile, allowing gene flow to occur between the species. Using transcriptomic data from multiple individuals of both nightingale species, we identified genomic islands of high differentiation (FST ) and of high divergence (Dxy ), and we analysed gene content and patterns of molecular evolution within these islands. Interestingly, we found that these islands were enriched for genes related to female meiosis and metabolism. The islands of high differentiation and divergence were also characterized by higher levels of linkage disequilibrium than the rest of the genome in both species indicating that they might be situated in genomic regions of low recombination. This study provides one of the first insights into genetic basis of hybrid female sterility in organisms with heterogametic females.

• Klíčová slova
• birds, genomic islands of differentiation, hybrid female sterility, oogenesis, speciation,
• MeSH
• chromozomy genetika   MeSH
• genetická variace MeSH
• genetické asociační studie * MeSH
• genomové ostrovy genetika   MeSH
• hybridizace genetická * MeSH
• meióza genetika   MeSH
• molekulární evoluce MeSH
• vazebná nerovnováha genetika   MeSH
• ženská infertilita genetika   MeSH
• zpěvní ptáci genetika   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) - craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia - have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population.

• Klíčová slova
• candidate gene, craniofacial dysmorphism, pediatric obstructive sleep apnea, skeletal anomaly, syndrome,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In the past years, dogs have served as a convenient natural model organism for longevity due to their similarity with humans concerning not only their environment but also the diseases and complications occurring in older age. Since many dog breeds have significantly shorter lifespan than their closely related breeds, identification of genes associated with longevity may help to elucidate its background and serve as a possible tool for selective breeding of long-living dogs. This genome-wide association study (GWAS) was undertaken to identify the candidate genes associated with longevity in Cavalier King Charles Spaniel individuals that have reached the age of more than 13 years. We described 15 SNPs localized in nine genes: B3GALNT1, NLRP1 like, PARP14, IQCJ-SCHIP1, COL9A1, COL19A1, SDHAF4, B3GAT2, and DIRC2 that are associated with longevity in purebred Cavalier King Charles Spaniels. These results are promising for future research and possible selective breeding of companion dogs with extended lifespan.

• Klíčová slova
• Cavalier King Charles Spaniel dog, Extending lifespan, GWAS, Longevity testing, Longevity-associated genes,
• Publikační typ
• časopisecké články MeSH

Plant-rhizobia symbiosis can activate key genes involved in regulating nodulation associated with biological nitrogen fixation (BNF). Although the general molecular basis of the BNF process is frequently studied, little is known about its intraspecific variability and the characteristics of its allelic variants. This study's main goals were to describe phenotypic and genotypic variation in the context of nitrogen fixation in red clover (Trifolium pretense L.) and identify variants in BNF candidate genes associated with BNF efficiency. Acetylene reduction assay validation was the criterion for selecting individual plants with particular BNF rates. Sequences in 86 key candidate genes were obtained by hybridization-based sequence capture target enrichment of plants with alternative phenotypes for nitrogen fixation. Two genes associated with BNF were identified: ethylene response factor required for nodule differentiation (EFD) and molybdate transporter 1 (MOT1). In addition, whole-genome population genotyping by double-digest restriction-site-associated sequencing (ddRADseq) was performed, and BNF was evaluated by the natural 15N abundance method. Polymorphisms associated with BNF and reflecting phenotype variability were identified. The genetic structure of plant accessions was not linked to BNF rate of measured plants. Knowledge of the genetic variation within BNF candidate genes and the characteristics of genetic variants will be beneficial in molecular diagnostics and breeding of red clover.

• Klíčová slova
• associated genes, associated polymorphisms, biological nitrogen fixation, genome-wide association, red clover,
• MeSH
• alely MeSH
• fenotyp MeSH
• fixace dusíku genetika   MeSH
• genotyp MeSH
• interakce mikroorganismu a hostitele MeSH
• kořeny rostlin genetika   mikrobiologie   MeSH
• polymorfismus genetický * MeSH
• Rhizobium fyziologie   MeSH
• rostlinné geny genetika   MeSH
• sekvenční analýza DNA metody   MeSH
• symbióza genetika   MeSH
• Trifolium genetika   mikrobiologie   MeSH
• Publikační typ
• časopisecké články MeSH

Establishing links between phenotypes and molecular variants is of central importance to accelerate genetic improvement of economically important plant species. Our work represents the first genome-wide association study to the inherently complex and currently poorly understood genetic architecture of industrially relevant wood traits. Here, we employed an Illumina Infinium 34K single nucleotide polymorphism (SNP) genotyping array that generated 29,233 high-quality SNPs in c. 3500 broad-based candidate genes within a population of 334 unrelated Populus trichocarpa individuals to establish genome-wide associations. The analysis revealed 141 significant SNPs (α ≤ 0.05) associated with 16 wood chemistry/ultrastructure traits, individually explaining 3-7% of the phenotypic variance. A large set of associations (41% of all hits) occurred in candidate genes preselected for their suggested a priori involvement with secondary growth. For example, an allelic variant in the FRA8 ortholog explained 21% of the total genetic variance in fiber length, when the trait's heritability estimate was considered. The remaining associations identified SNPs in genes not previously implicated in wood or secondary wall formation. Our findings provide unique insights into wood trait architecture and support efforts for population improvement based on desirable allelic variants.

• Klíčová slova
• Populus, association genetics, cellulose, lignin, single nucleotide polymorphism (SNP), wood traits, wood ultrastructure,
• MeSH
• alely MeSH
• buněčná stěna MeSH
• dřevo * růst a vývoj   metabolismus   ultrastruktura   MeSH
• fenotyp * MeSH
• genetické asociační studie MeSH
• genom rostlinný * MeSH
• genotyp * MeSH
• jednonukleotidový polymorfismus * MeSH
• Populus genetika   růst a vývoj   metabolismus   ultrastruktura   MeSH
• rostlinné geny * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

The Feline coronavirus (FCoV) can cause a fatal disease, the Feline Infectious Peritonitis. Persistent shedders represent the most important source of infection. The role of the host in FCoV fecal shedding is unknown. The objective of this study was to develop gene markers and to test their associations with FCoV shedding patterns. Fecal samples were taken from 57 cats of 12 breeds on the day 0 and after 2, 4 and 12 months. Variation from persistent and/or high-intensity shedding to no shedding was observed. Thirteen immunity-related genes were selected as functional and positional/functional candidates. Positional candidates were selected in a candidate region detected by a GWAS analysis. Tens to hundreds of single nucleotide polymorphisms (SNPs) per gene were identified using next generation sequencing. Associations with different phenotypes were assessed by chi-square and Fisher's exact tests. SNPs of one functional and one positional candidate (NCR1 and SLX4IP, respectively) and haplotypes of four genes (SNX5, NCR2, SLX4IP, NCR1) were associated with FCoV shedding at pcorected < 0.01. Highly significant associations were observed for extreme phenotypes (persistent/high-intensity shedders and non-shedders) suggesting that there are two major phenotypes associated with different genotypes, highly susceptible cats permanently shedding high amounts of viral particles and resistant non-shedders.

• Klíčová slova
• association study, fecal shedding patterns, feline enteric coronavirus, genetic susceptibility, immunity-related candidate genes, polymerase-chain reaction,
• Publikační typ
• časopisecké články MeSH

We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of "candidate ciliopathy genes." From this list, 32 genes encoded proteins predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology. Histological and morphological evidence of phenotypes found in ciliopathies in knockout mouse lines are presented as examples (genes Abi2, Wdr62, Ap4e1, Dync1li1, and Prkab1). Phenotyping data and descriptions generated on IMPC mouse line are useful for mechanistic studies, target discovery, rare disease diagnosis, and preclinical therapeutic development trials. Here we demonstrate the effective use of the IMPC phenotype data to uncover genes with no previous role in ciliary biology, which may be clinically relevant for identification of novel disease genes implicated in ciliopathies.

• MeSH
• cilie genetika   MeSH
• ciliopatie * genetika   MeSH
• databáze faktografické MeSH
• genový knockout MeSH
• myši knockoutované MeSH
• myši MeSH
• proteiny buněčného cyklu MeSH
• proteiny nervové tkáně MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• proteiny buněčného cyklu MeSH
• proteiny nervové tkáně MeSH
• WDR62 protein, mouse MeSH Prohlížeč