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1.
Nat Commun ; 11(1): 4778, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963241

RESUMO

Obtaining genetic variation information from indica rice hybrid parents and identification of loci associated with heterosis are important for hybrid rice breeding. Here, we resequence 1,143 indica accessions mostly selected from the parents of superior hybrid rice cultivars of China, identify genetic variations, and perform kinship analysis. We find different hybrid rice crossing patterns between 3- and 2-line superior hybrid lines. By calculating frequencies of parental variation differences (FPVDs), a more direct approach for studying rice heterosis, we identify loci that are linked to heterosis, which include 98 in superior 3-line hybrids and 36 in superior 2-line hybrids. As a proof of concept, we find two accessions harboring a deletion in OsNramp5, a previously reported gene functioning in cadmium absorption, which can be used to mitigate rice grain cadmium levels through hybrid breeding. Resource of indica rice genetic variation reported in this study will be valuable to geneticists and breeders.


Assuntos
Variação Genética , Vigor Híbrido/genética , Oryza/genética , Cruzamento , Proteínas de Transporte de Cátions/genética , China , Cruzamentos Genéticos , Deleção de Genes , Genes de Plantas , Hibridização Genética , Oryza/classificação , Filogenia , Proteínas de Plantas/genética , Polimorfismo de Nucleotídeo Único
2.
Nat Commun ; 11(1): 4468, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901021

RESUMO

Speciation constrains the flow of genetic information between populations of sexually reproducing organisms. Gaining control over mechanisms of speciation would enable new strategies to manage wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such control would provide safe biocontainment of transgenes and gene drives. Here, we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. EGI couples a dominant lethal transgene with a recessive resistance allele. Strains homozygous for both elements are fertile and fecund when they mate with similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. EGI genotypes can also be tuned to cause hybrid lethality at different developmental life-stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be engineered to be mutually incompatible with wild-type and with each other. EGI is a simple and robust approach in multiple sexually reproducing organisms.


Assuntos
Drosophila melanogaster/genética , Engenharia Genética/métodos , Especiação Genética , Animais , Animais Geneticamente Modificados , Cruzamentos Genéticos , Feminino , Genes de Insetos , Genes Letais , Genótipo , Hibridização Genética , Masculino , Modelos Genéticos , Transgenes
3.
PLoS Biol ; 18(8): e3000756, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745139

RESUMO

Recognition of self and nonself is important for outcrossing organisms, and different mating types establish the barrier against self-mating. In the unicellular ciliate T. thermophila, mating type determination requires complex DNA rearrangements at a single mat locus during conjugation to produce a type-specific gene pair (MTA and MTB) for 1 of 7 possible mating types. Surprisingly, we found that decreased expression of the DNA breakage-repair protein Ku80 at late stages of conjugation generated persistent selfing phenotype in the progeny. DNA analysis revealed multiple mating-type gene pairs as well as a variety of mis-paired, unusually arranged mating-type genes in these selfers that resemble some proposed rearrangement intermediates. They are found also in normal cells during conjugation and are lost after 10 fissions but are retained in Ku mutants. Silencing of TKU80 or TKU70-2 immediately after conjugation also generated selfing phenotype, revealing a hidden DNA rearrangement process beyond conjugation. Mating reactions between the mutant and normal cells suggest a 2-component system for self-nonself-recognition through MTA and MTB genes.


Assuntos
DNA de Protozoário/genética , Rearranjo Gênico , Autoantígeno Ku/genética , Proteínas de Protozoários/genética , Tetrahymena thermophila/genética , Conjugação Genética , Cruzamentos Genéticos , DNA de Protozoário/metabolismo , Expressão Gênica , Inativação Gênica , Autoantígeno Ku/metabolismo , Fenótipo , Proteínas de Protozoários/metabolismo , Reprodução , Tetrahymena thermophila/metabolismo
4.
Mol Genet Genomics ; 295(5): 1187-1195, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32476049

RESUMO

Cowpea (Vigna unguiculate (L.) Walp.) is a worldwide important multifunctional legume crop for food grain, vegetable, fodder, and cover crop. Nevertheless, only limited research has been conducted on agronomic traits. Here, we report quantitative trait locus (QTL) analysis of the days to flowering (DTF) and plant height (PH) using a dense SNP linkage map recently developed from a recombinant inbred line (RIL) population derived from a cross between Golden Eye Cream and IT98K-476-8. The population was phenotyped for DTF and PH through field and greenhouse trials under two environments. The QTLs controlling these traits were mapped using multiple-environment combined and individual trial phenotypic data. The combined data analysis identified one major QTL (qDTF9.1) for DTF, and one major QTL (qPH9.1) and a minor QTL (qPH4.1) for PH. qDTF9.1 and qPH9.1 were adjacent to each other on Chromosome 9 and each explained 29.3% and 29.5% of the phenotypic variation (PVE), respectively. The individual trial data analysis identified a minor QTL (qDTF2.1) on Chromosome 2 for DTF and two minor QTLs (qPH4.1 and qPH4.2) on Chromosome 4 for PH, while the major QTLs, qDTF9.1 and qPH9.1, were consistently identified in all trials conducted. Epistasis analysis revealed that qDTF9.1 interacted with one locus on Chromosome 4, contributed 50% of the PVE, and qPH9.1 interacted with one locus on each of Chromosomes 4 and 6, contributing 30% and 23% of the PVE, respectively, suggesting that epistasis plays an important role in the trait performance. These results, therefore, provide a deeper understanding of the genetic architecture of plant DTF and PH, and molecular tools necessary for cloning the genes and for enhanced cowpea breeding.


Assuntos
Mapeamento Cromossômico/métodos , Locos de Características Quantitativas , Vigna/fisiologia , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Epistasia Genética , Flores/genética , Flores/crescimento & desenvolvimento , Fenótipo , Polimorfismo de Nucleotídeo Único , Vigna/anatomia & histologia , Vigna/genética
5.
Nat Rev Genet ; 21(7): 428-444, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32424311

RESUMO

Knowing phylogenetic relationships among species is fundamental for many studies in biology. An accurate phylogenetic tree underpins our understanding of the major transitions in evolution, such as the emergence of new body plans or metabolism, and is key to inferring the origin of new genes, detecting molecular adaptation, understanding morphological character evolution and reconstructing demographic changes in recently diverged species. Although data are ever more plentiful and powerful analysis methods are available, there remain many challenges to reliable tree building. Here, we discuss the major steps of phylogenetic analysis, including identification of orthologous genes or proteins, multiple sequence alignment, and choice of substitution models and inference methodologies. Understanding the different sources of errors and the strategies to mitigate them is essential for assembling an accurate tree of life.


Assuntos
Genoma , Genômica , Modelos Genéticos , Filogenia , Animais , Biologia Computacional/métodos , Cruzamentos Genéticos , Bases de Dados Genéticas , Evolução Molecular , Heterogeneidade Genética , Genômica/métodos , Humanos
6.
PLoS One ; 15(5): e0233382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32437473

RESUMO

Experimental corn hybrids are created in plant breeding programs by crossing two parents, so-called inbred and tester, together. Identification of best parent combinations for crossing is challenging since the total number of possible cross combinations of parents is large and it is impractical to test all possible cross combinations due to limited resources of time and budget. In the 2020 Syngenta Crop Challenge, Syngenta released several large datasets that recorded the historical yield performances of around 4% of total cross combinations of 593 inbreds with 496 testers which were planted in 280 locations between 2016 and 2018 and asked participants to predict the yield performance of cross combinations of inbreds and testers that have not been planted based on the historical yield data collected from crossing other inbreds and testers. In this paper, we present a collaborative filtering method which is an ensemble of matrix factorization method and a neural network to solve this problem. Our computational results suggested that the proposed model significantly outperformed other models such as deep factorization machines (DeepFM), generalized matrix factorization (GMF), LASSO, random forest (RF), and neural networks. Presented method and results were produced within the 2020 Syngenta Crop Challenge.


Assuntos
Cruzamentos Genéticos , Modelos Genéticos , Melhoramento Vegetal , Zea mays/genética , Hibridização Genética , Redes Neurais de Computação
7.
PLoS One ; 15(5): e0233885, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470029

RESUMO

In the Danio species, interspecific hybridization has been conducted in several combinations. Among them, only the hybrid between a zebrafish (D. rerio) female and a spotted danio (D. nigrofasciatus) male was reported to be fertile. However, beyond these investigations, by means of reproductive biology, gametes of the hybrid have also not been investigated genetically. For this study, we induced a hybrid of the D. rerio female and D. nigrofasciatus male in order to study its developmental capacity, reproductive performance and gametic characteristics. Its hybrid nature was genetically verified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the rhodopsin gene. Almost all the hybrids (36/37) were males, and only one was female. Developing oocytes were observed in the hybrid female, but ovulated eggs have not been obtained thus far. Microscopic observation revealed various head sizes of sperm in the hybrid males. Flow cytometry showed that the hybrid males generated aneuploid sperm with various ploidy levels up to diploidy. In backcrosses between D. rerio females and hybrid males, fertilization rates were significantly lower than the control D. rerio, and most resultant progeny with abnormal appearance exhibited various kinds of aneuploidies ranging from haploidy to triploidy, but only one viable progeny, which survived more than four months, was triploid. This suggested the contribution of fertile diploid sperm of the hybrid male to successful fertilization and development.


Assuntos
Aneuploidia , Fertilização/fisiologia , Hibridização Genética , Espermatozoides/fisiologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia , Animais , Cruzamentos Genéticos , DNA/genética , Feminino , Masculino , Ovário/citologia , Ploidias , Rodopsina/genética , Razão de Masculinidade , Espermatozoides/citologia
8.
PLoS Genet ; 16(5): e1008766, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32365090

RESUMO

Complex traits are known to be influenced by a combination of environmental factors and rare and common genetic variants. However, detection of such multivariate associations can be compromised by low statistical power and confounding by population structure. Linear mixed effects models (LMM) can account for correlations due to relatedness but have not been applicable in high-dimensional (HD) settings where the number of fixed effect predictors greatly exceeds the number of samples. False positives or false negatives can result from two-stage approaches, where the residuals estimated from a null model adjusted for the subjects' relationship structure are subsequently used as the response in a standard penalized regression model. To overcome these challenges, we develop a general penalized LMM with a single random effect called ggmix for simultaneous SNP selection and adjustment for population structure in high dimensional prediction models. We develop a blockwise coordinate descent algorithm with automatic tuning parameter selection which is highly scalable, computationally efficient and has theoretical guarantees of convergence. Through simulations and three real data examples, we show that ggmix leads to more parsimonious models compared to the two-stage approach or principal component adjustment with better prediction accuracy. Our method performs well even in the presence of highly correlated markers, and when the causal SNPs are included in the kinship matrix. ggmix can be used to construct polygenic risk scores and select instrumental variables in Mendelian randomization studies. Our algorithms are available in an R package available on CRAN (https://cran.r-project.org/package=ggmix).


Assuntos
Algoritmos , Estudo de Associação Genômica Ampla/métodos , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Animais , Simulação por Computador , Cruzamentos Genéticos , Genética Populacional/métodos , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Leishmania tropica/genética , Leishmaniose Cutânea/genética , Modelos Lineares , Camundongos , Camundongos Endogâmicos , Herança Multifatorial/genética , Mycobacterium bovis , Dinâmica Populacional , Tamanho da Amostra , Software , Tuberculose/genética , Tuberculose/patologia
9.
Nat Commun ; 11(1): 2412, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415063

RESUMO

Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here, we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2ARS2 protein in association with splicing factors, which recruit RNA processing and chromatin-modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs.


Assuntos
Regulação Fúngica da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Íntrons , RNA Longo não Codificante/metabolismo , Schizosaccharomyces/genética , Processamento Alternativo , Cromatina/metabolismo , Cruzamentos Genéticos , Inativação Gênica , Genoma Fúngico , Proteínas de Choque Térmico/genética , Interferência de RNA , Sítios de Splice de RNA , RNA Longo não Codificante/genética , RNA-Seq , Schizosaccharomyces/metabolismo , Transcrição Genética
10.
Invest Ophthalmol Vis Sci ; 61(5): 25, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32416604

RESUMO

Purpose: Ophthalmic disorders are among the most prevalent Down syndrome (DS) comorbidities. Therefore, when studying mouse models of DS, ignoring how vision is affected can lead to misinterpretation of results from assessments dependent on the integrity of the visual system. Here, we used imaging and electroretinography (ERG) to study eye structure and function in two important mouse models of DS: Ts65Dn and Dp(16)1Yey/+. Methods: Cornea and anterior segment were examined with a slit-lamp. Thickness of retinal layers was quantified by optical coherence tomography (OCT). Eye and lens dimensions were measured by magnetic resonance imaging (MRI). Retinal vasculature parameters were assessed by bright field and fluorescent imaging, and by retinal flat-mount preparations. Ganzfeld ERG responses to flash stimuli were used to assess retinal function in adult mice. Results: Total retinal thickness is significantly increased in Ts65Dn and Dp(16)1Yey/+ compared with control mice, because of increased thickness of inner retinal layers, including the inner nuclear layer (INL). Increased retinal vessel caliber was found in both chromosomally altered mice when compared with controls. ERG responses in Ts65Dn and Dp(16)1Yey/+ mice showed subtle alterations compared with controls. These, however, seemed to be unrelated to the thickness of the INL, but instead dependent on the anesthetic agent used (ketamine, tribromoethanol, or urethane). Conclusions: We provide evidence of retinal alterations in Ts65Dn and Dp(16)1Yey/+ mice that are similar to those reported in persons with DS. Our ERG results are also a reminder that consideration should be given to the choice of anesthetic agents in such experiments.


Assuntos
Cromossomos de Mamíferos/genética , Modelos Animais de Doenças , Síndrome de Down/fisiopatologia , Retina/fisiopatologia , Animais , Córnea/fisiologia , Cruzamentos Genéticos , Síndrome de Down/genética , Eletrorretinografia , Feminino , Angiofluoresceinografia , Cristalino/fisiologia , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Midriáticos/administração & dosagem , Estimulação Luminosa , Pupila/efeitos dos fármacos , Vasos Retinianos/fisiopatologia , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Campos Visuais/fisiologia
11.
Gene ; 747: 144671, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304782

RESUMO

In diploid organisms, each gene locus is composed of two parental alleles, which would interact with each other for determining the phenotypic variation. Better understanding of the allele-specific expression (ASE) in farm animals is much important to explore the genetic basis underlying economically important traits, which have been poorly understood yet. In this study, genome-wide analysis was applied to explore the spatiotemporal pattern of ASE in the F1 hybrids of chicken. First, meat- and egg-type chickens were selected for producing a full-sib F1 hybrid population (n = 57). Then, genome resequencing of two parents and 38 offspring were performed and liver and breast muscle samples (n = 38) were subjected to strand-specific RNA sequencing (ssRNA-seq) for ASE detection at 1, 28, and 56 days of age, respectively. The results accurately identified a total of 465 informative genes that could be distinguished with respect to their parental origins. There were 0.4% - 4.1% of informative genes showing ASE, and 57 of them were found across different tissues and time points. Besides, most ASE genes in chickens were tissue-specific, and no matter what the time-point pattern of one ASE gene, the same parental allele of this gene almost showed consistently higher or lower expression across all time points in the same type tissue. In conclusion, this study indicated that most of ASE genes were tissue-specific and time-dependent.


Assuntos
Alelos , Galinhas/genética , Cruzamentos Genéticos , Ovos , Regulação da Expressão Gênica , Genoma , Hibridização Genética , Carne , Animais , Feminino , Masculino , Especificidade de Órgãos/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Tempo
12.
PLoS One ; 15(4): e0228357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275662

RESUMO

Increasingly, studies are revealing that endocrine disrupting chemicals (EDCs) can alter animal behavior. Early life exposure to EDCs may permanently alter phenotypes through to adulthood. In addition, the effects of EDCs may not be isolated to a single generation - offspring may indirectly be impacted, via non-genetic processes. Here, we analyzed the effects of paternal atrazine exposure on behavioral traits (distance moved, exploration, bottom-dwelling time, latency to enter the top zone, and interaction with a mirror) and whole-brain mRNA of genes involved in the serotonergic system regulation (slc6a4a, slc6a4b, htr1Aa, htr1B, htr2B) of zebrafish (Danio rerio). F0 male zebraFIsh were exposed to atrazine at 0.3, 3 or 30 part per billion (ppb) during early juvenile development, the behavior of F1 progeny was tested at adulthood, and the effect of 0.3 ppb atrazine treatment on mRNA transcription was quantified. Paternal exposure to atrazine significantly reduced interactions with a mirror (a proxy for aggression) and altered the latency to enter the top zone of a tank in unexposed F1 offspring. Bottom-dwelling time (a proxy for anxiety) also appeared to be somewhat affected, and activity (distance moved) was reduced in the context of aggression. slc6a4a and htr1Aa mRNA transcript levels were found to correlate positively with anxiety levels in controls, but we found that this relationship was disrupted in the 0.3 ppb atrazine treatment group. Overall, paternal atrazine exposure resulted in alterations across a variety of behavioral traits and showed signs of serotonergic system dysregulation, demonstrating intergenerational effects. Further research is needed to explore transgenerational effects on behavior and possible mechanisms underpinning behavioral effects.


Assuntos
Comportamento Animal/efeitos dos fármacos , Herbicidas/toxicidade , Exposição Paterna , Serotonina/metabolismo , Peixe-Zebra/fisiologia , Animais , Atrazina/toxicidade , Cruzamentos Genéticos , Comportamento Exploratório/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento
13.
PLoS One ; 15(4): e0231129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240263

RESUMO

Aegilops umbellulata is a wild diploid wheat species with the UU genome that is an important genetic resource for wheat breeding. To exploit new synthetic allohexaploid lines available as bridges for wheat breeding, a total of 26 synthetic hexaploid lines were generated through crossing between the durum wheat cultivar Langdon and 26 accessions of Ae. umbellulata. In nascent synthetic hexaploids with the AABBUU genome, the presence of the set of seven U-genome chromosomes was confirmed with U-genome chromosome-specific markers developed based on RNA-seq-derived data from Ae. umbellulata. The AABBUU synthetic hexaploids showed large variations in flowering- and morphology-related traits, and these large variations transmitted well from the parental Ae. umbellulata accessions. However, the variation ranges in most traits examined were reduced under the AABBUU hexaploid background compared with under the diploid parents. The AABBUU and AABBDD synthetic hexaploids were clearly discriminated by several morphological traits, and an increase of plant height and in the number of spikes and a decrease of spike length were commonly observed in the AABBUU synthetics. Thus, interspecific differences in several morphological traits between Ae. umbellulata and A. tauschii largely affected the basic plant architecture of the synthetic hexaploids. In conclusion, the AABBUU synthetic hexaploid lines produced in the present study are useful resources for the introgression of desirable genes from Ae. umbellulata to common wheat.


Assuntos
Aegilops/genética , Cruzamentos Genéticos , Diploide , Variação Genética , Genoma de Planta , Poliploidia , Triticum/genética , Cromossomos de Plantas/genética , Ecótipo , Marcadores Genéticos , Dureza , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Análise de Componente Principal , Característica Quantitativa Herdável , Sementes/genética , Especificidade da Espécie
14.
PLoS One ; 15(4): e0230422, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271764

RESUMO

The inability of beef cattle to maintain full term pregnancies has become an economic concern for the beef industry. Herd management and nutritional improvements have alleviated environmental impacts on embryonic and fetal loss, yet additional gains can be made through genomic selection. The objectives of this study were to identify loci and gene-sets in crossbred beef heifers associated with the number of services required to become pregnant (TBRD) and heifer conception rate at first service (HCR1). Heifers (n = 709) from a commercial beef operation underwent one round of artificial insemination, before exposure to bulls for natural service for 50 days. Pregnancy and time of conception was determined by ultrasound 35 days after the breeding season. Heifers were genotyped using the GeneSeek (Lincoln, NE) Bovine GGP50K BeadChip prior to genome-wide association analyses (GWAA) conducted using an EIGENSTRAT-like model to identify loci associated (P < 1 × 10-5) with TBRD and HCR1. One locus was associated (P = 8.97 × 10-6) with TBRD on BTA19 and included the positional candidate gene ASIC2, which is differentially expressed in the endometrium of fertility classified heifers, and the positional candidate gene, SPACA3. Gene-set enrichment analyses using SNP (GSEA-SNP) data, was performed and identified one gene-set, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen as enriched (NES = 3.15) with TBRD and contained nine leading edge genes that contributed to the enrichment of the gene set. The enriched gene-set is involved in catalyzing oxidation-reduction reactions, which have been associated with oxidative stressors impacting pregnancy success. No loci were associated nor gene-sets enriched with HCR1. Identification of loci, positional candidate genes, gene-sets and leading edge genes enriched for fertility facilitate genomic selection that allows producers to select for reproductively superior cattle, reduce costs associated with infertility, and increase percent calf crop.


Assuntos
Bovinos/genética , Loci Gênicos , Hibridização Genética/genética , Taxa de Gravidez , Prenhez , Reprodução/genética , Animais , Cruzamento , Quimera/genética , Cruzamentos Genéticos , Feminino , Fertilidade/genética , Fertilização/genética , Estudos de Associação Genética/veterinária , Técnicas de Genotipagem , Masculino , Polimorfismo de Nucleotídeo Único , Gravidez , Prenhez/genética
15.
Arterioscler Thromb Vasc Biol ; 40(6): 1491-1509, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295421

RESUMO

OBJECTIVE: Galectin-3 (formerly known as Mac-2), encoded by the LGALS3 gene, is proposed to regulate macrophage adhesion, chemotaxis, and apoptosis. We investigated the role of galectin-3 in determining the inflammatory profile of macrophages and composition of atherosclerotic plaques. Approach and Results: We observed increased accumulation of galectin-3-negative macrophages within advanced human, rabbit, and mouse plaques compared with early lesions. Interestingly, statin treatment reduced galectin-3-negative macrophage accrual in advanced plaques within hypercholesterolemic (apolipoprotein E deficient) Apoe-/- mice. Accordingly, compared with Lgals3+/+:Apoe-/- mice, Lgals3-/-:Apoe-/- mice displayed altered plaque composition through increased macrophage:smooth muscle cell ratio, reduced collagen content, and increased necrotic core area, characteristics of advanced plaques in humans. Additionally, macrophages from Lgals3-/- mice exhibited increased invasive capacity in vitro and in vivo. Furthermore, loss of galectin-3 in vitro and in vivo was associated with increased expression of proinflammatory genes including MMP (matrix metalloproteinase)-12, CCL2 (chemokine [C-C motif] ligand 2), PTGS2 (prostaglandin-endoperoxide synthase 2), and IL (interleukin)-6, alongside reduced TGF (transforming growth factor)-ß1 expression and consequent SMAD signaling. Moreover, we found that MMP12 cleaves macrophage cell-surface galectin-3 resulting in the appearance of a 22-kDa fragment, whereas plasma levels of galectin-3 were reduced in Mmp12-/-:Apoe-/- mice, highlighting a novel mechanism where MMP12-dependent cleavage of galectin-3 promotes proinflammatory macrophage polarization. Moreover, galectin-3-positive macrophages were more abundant within plaques of Mmp12-/-:Apoe-/- mice compared with Mmp12+/+:Apoe-/- animals. CONCLUSIONS: This study reveals a prominent protective role for galectin-3 in regulating macrophage polarization and invasive capacity and, therefore, delaying plaque progression.


Assuntos
Aterosclerose/patologia , Galectina 3/fisiologia , Macrófagos/fisiologia , Animais , Cruzamentos Genéticos , Feminino , Galectina 3/análise , Galectina 3/deficiência , Humanos , Inflamação/patologia , Macrófagos/química , Macrófagos/patologia , Masculino , Metaloproteinase 12 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/metabolismo
16.
Arterioscler Thromb Vasc Biol ; 40(6): 1523-1532, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32321308

RESUMO

OBJECTIVE: Although the molecular components of circadian rhythms oscillate in discrete cellular components of the vasculature and many aspects of vascular function display diurnal variation, the cellular connections between the molecular clock and inflammatory cardiovascular diseases remain to be elucidated. Previously we have shown that pre- versus postnatal deletion of Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1), the nonredundant core clock gene has contrasting effects on atherogenesis. Here we investigated the effect of myeloid cell Bmal1 deletion on atherogenesis and abdominal aortic aneurysm formation in mice. Approach and Results: Mice lacking Bmal1 in myeloid cells were generated by crossing Bmal1 flox/flox mice with lysozyme 2 promoter-driven Cre recombinase mice on a hyperlipidemic low-density lipoprotein receptor-deficient background and were fed on a high-fat diet to induce atherosclerosis. Atherogenesis was restrained, concomitant with a reduction of aortic proinflammatory gene expression in myeloid cell Bmal1 knockout mice. Body weight, blood pressure, blood glucose, triglycerides, and cholesterol were unaltered. Similarly, myeloid cell depletion of Bmal1 also restrained Ang II (angiotensin II) induced formation of abdominal aortic aneurysm in hyperlipidemic mice. In vitro, RNA-Seq analysis demonstrated a proinflammatory response in cultured macrophages in which there was overexpression of Bmal1. CONCLUSIONS: Myeloid cell Bmal1 deletion retards atherogenesis and restrains the formation of abdominal aortic aneurysm and may represent a potential therapeutic target for inflammatory cardiovascular diseases.


Assuntos
Fatores de Transcrição ARNTL/deficiência , Fatores de Transcrição ARNTL/fisiologia , Aneurisma da Aorta Abdominal/prevenção & controle , Aterosclerose/prevenção & controle , Hiperlipidemias/complicações , Células Mieloides/química , Fatores de Transcrição ARNTL/genética , Angiotensina II/farmacologia , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aterosclerose/etiologia , Aterosclerose/patologia , Células Cultivadas , Cruzamentos Genéticos , Dieta Hiperlipídica , Deleção de Genes , Expressão Gênica , Hiperlipidemias/etiologia , Inflamação , Integrases/genética , Macrófagos Peritoneais/química , Macrófagos Peritoneais/fisiologia , Camundongos , Camundongos Knockout , Muramidase/genética , Regiões Promotoras Genéticas/genética , Receptores de LDL/deficiência , Receptores de LDL/genética
17.
Cytogenet Genome Res ; 160(1): 47-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32172236

RESUMO

The chromosomal constitution of 9 dwarf (D) and 8 semidwarf (SD) lines derived by crossing hexaploid Triticale line NA-75 (AABBRR, 2n = 6x = 42) with Triticumaestivum (AABBDD, 2n = 6x = 42) cv. Chinese Spring was investigated using molecular cytogenetic techniques: fluorescence in situ hybridization and genomic in situ hybridization. A wheat-rye translocation (T4DS.7RL), 8 substitution lines, and a ditelosomic addition line (7RSdt) were identified. In the substitution lines, 1, 2, or 4 pairs of wheat chromosomes, belonging to the A, B, or D genome, were replaced by rye chromosomes. Substitutions between chromosomes belonging to different wheat genomes [5B(5A), 1D(1B)] also occurred. The lines were genetically stable, each carrying 42 chromosomes, except the wheat-rye ditelosomic addition line, which carried 21 pairs of wheat chromosomes and 1 pair of rye telocentric chromosomes (7RS). The chromosome pairing behavior of the lines was studied during metaphase I of meiosis. The chromosome pairing level and the number of ring bivalents were different for each line. Besides rod bivalents, univalent and multivalent associations (tri- and quadrivalents) were also detected. The main goal of the experiment was to develop genetically stable wheat/Triticale recombinant lines carrying chromosomes/chromatin fragments originating from the R genome of Triticale line NA-75. Introgression of rye genes into hexaploid wheat can broaden its genetic diversity, and the newly developed lines can be used in wheat breeding programs.


Assuntos
Meiose/genética , Triticale/genética , Triticum/genética , Cromatina/metabolismo , Pareamento Cromossômico , Cromossomos de Plantas , Cruzamentos Genéticos , Análise Citogenética , Genes de Plantas , Variação Genética , Hibridização In Situ , Hibridização in Situ Fluorescente , Metáfase , Ploidias , Secale/genética , Especificidade da Espécie , Translocação Genética
18.
PLoS One ; 15(3): e0230326, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160264

RESUMO

Milling properties and flour color are essential selection criteria in soft wheat breeding. However, high phenotypic screening costs restrict selection to relatively few breeding lines in late generations. To achieve marker-based selection of these traits in early generations, we performed genetic dissection of quality traits using three doubled haploid populations that shared the high-quality soft wheat variety Kitahonami as the paternal parent. An amplicon sequencing approach allowed effective construction of well-saturated linkage maps of the populations. Marker-based heritability estimates revealed that target quality traits had relatively high values, indicating the possibility of selection in early generations. Taking advantage of Chinese Spring reference sequences, joint linkage maps of the three populations were generated. Based on the maps, multifamily quantitative trait locus (QTL) analysis revealed a total of 86 QTLs for ten traits investigated. In terms of target quality traits, 12 QTLs were detected for flour yield, and 12 were detected for flour redness (a* value). Among these QTLs, six for flour yield and nine for flour a* were segregating in more than two populations. Some relationships among traits were explained by QTL collocations on chromosomes, especially group 7 chromosomes. Ten different ideotypes with various combinations of favorable alleles for the flour yield and flour a* QTLs were generated. Phenotypes of derivatives from these ideotypes were predicted to design ideal genotypes for high-quality wheat. Simulations revealed the possibility of breeding varieties with better quality than Kitahonami.


Assuntos
Farinha , Melhoramento Vegetal/métodos , Locos de Características Quantitativas , Triticum/genética , Alelos , Mapeamento Cromossômico , Cruzamentos Genéticos , Ligação Genética , Haploidia , Fenótipo
19.
PLoS One ; 15(3): e0229912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191715

RESUMO

The flag leaf is the main organ of photosynthesis during grain-filling period of wheat, and flag leaf-related traits affect plant morphology and yield potential. In this study, two BC3F6 introgression line (IL) populations derived from the common recipient parent Lumai 14 with Jing 411 and Shaanhan 8675, respectively, were used to map quantitative trait loci (QTL) for flag leaf length (FLL), flag leaf width (FLW), flag leaf area (FLA) and chlorophyll content (CC) at flowering stage and 15 and 20 days after anthesis (DAA) in 2016-2017 (E1) and 2017-2018 (E2) two environments. A total of 14 and 15 QTLs for flag leaf-related traits were detected in Lumai 14 / Jing 411 and Lumai 14 / Shaanhan 8675 populations, respectively. Among them, Both QFLW-6A and QFLA-6A were detected in Lumai 14 / Jing 411 population under E2 and in Lumai 14 / Shaanhan 8675 population under E1 and E2 environments, respectively. QCCS2-3A from Lumai 14 / Jing 411 population and QCCS3-1A, QFLL-4A and QFLL-6A from Lumai 14 / Shaanhan 8675 population were repeatedly identified under two tested environments. Moreover, eight QTL clusters controlling flag leaf-related traits were identified, which provided a genetic basis for significant correlations in phenotype among these traits. On the other hand, positive alleles of QFLW-6A for FLW detected in two populations were derived from their donors. Eighteen lines and 44 lines carried this QTL were found in Lumai 14 / Jing 411 and Lumai 14 / Shaanhan 8675 populations, respectively. The means of FLW in these lines were wider than that of the recipient parent, Lumai 14, in two environments, suggesting that QFLW-6A played an important role for increasing FLW. The IL 124 in Lumai 14 / Jing 411 population and the IL 59 and IL 127 in Lumai 14 / Shaanhan 8675 population had five, five and four donor chromosomal segments which carried no other QTL controlling FLW than QFLW-6A, respectively. And the FLWs of these lines were significantly greater than that of Lumai 14 under two environments. So these lines and their donor parent can be regarded as potential near-isogenic lines. Further, a synteny analysis found QFLW-6A was near the 574,283,851-574,283,613 bp fragment on chromosome 6A and 10 genes were in the range of 500 kb upstream and downstream of the fragment. These results provide the basis for identification of candidate gene and map-based cloning and functional verification of the QTL.


Assuntos
Cromossomos de Plantas/genética , Folhas de Planta/genética , Locos de Características Quantitativas/genética , Triticum/genética , Alelos , Clorofila/genética , Mapeamento Cromossômico , Cruzamentos Genéticos , Grão Comestível/genética , Genótipo , Fenótipo , Fotossíntese/genética , Folhas de Planta/anatomia & histologia , Triticum/crescimento & desenvolvimento
20.
PLoS One ; 15(3): e0226448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214345

RESUMO

Rapid Alkalinization Factors (RALFs) are cysteine-rich peptides ubiquitous within plant kingdom. They play multiple roles as hormonal signals in diverse processes, including root elongation, cell growth, pollen tube development, and fertilization. Their involvement in host-pathogen crosstalk as negative regulators of immunity in Arabidopsis has also been recognized. In addition, peptides homologous to RALF are secreted by different fungal pathogens as effectors during early stages of infection. Previous studies have identified nine RALF genes in the diploid strawberry (Fragaria vesca) genome. This work describes the genomic organization of the RALF gene families in commercial octoploid strawberry (Fragaria × ananassa) and the re-annotated genome of F. vesca, and then compares findings with orthologs in Arabidopsis thaliana. We reveal the presence of 15 RALF genes in F. vesca genotype Hawaii 4 and 50 in Fragaria x ananassa cv. Camarosa, showing a non-homogenous localization of genes among the different Fragaria x ananassa subgenomes. Expression analysis of Fragaria x ananassa RALF genes upon infection with Colletotrichum acutatum or Botrytis cinerea showed that FanRALF3-1 was the only fruit RALF gene upregulated after fungal infection. In silico analysis was used to identify distinct pathogen inducible elements upstream of the FanRALF3-1 gene. Agroinfiltration of strawberry fruit with deletion constructs of the FanRALF3-1 promoter identified a 5' region required for FanRALF3-1 expression in fruit, but failed to identify a region responsible for fungal induced expression.


Assuntos
Botrytis , Colletotrichum , Cruzamentos Genéticos , Fragaria , Frutas , Família Multigênica , Proteínas de Neoplasias , Doenças das Plantas , Proteínas de Plantas , Fragaria/genética , Fragaria/microbiologia , Frutas/genética , Frutas/microbiologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
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