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1.
Nat Commun ; 11(1): 4374, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873787

RESUMO

Oncogene amplification, a major driver of cancer pathogenicity, is often mediated through focal amplification of genomic segments. Recent results implicate extrachromosomal DNA (ecDNA) as the primary driver of focal copy number amplification (fCNA) - enabling gene amplification, rapid tumor evolution, and the rewiring of regulatory circuitry. Resolving an fCNA's structure is a first step in deciphering the mechanisms of its genesis and the fCNA's subsequent biological consequences. We introduce a computational method, AmpliconReconstructor (AR), for integrating optical mapping (OM) of long DNA fragments (>150 kb) with next-generation sequencing (NGS) to resolve fCNAs at single-nucleotide resolution. AR uses an NGS-derived breakpoint graph alongside OM scaffolds to produce high-fidelity reconstructions. After validating its performance through multiple simulation strategies, AR reconstructed fCNAs in seven cancer cell lines to reveal the complex architecture of ecDNA, a breakage-fusion-bridge and other complex rearrangements. By reconstructing the rearrangement signatures associated with an fCNA's generative mechanism, AR enables a more thorough understanding of the origins of fCNAs.


Assuntos
Amplificação de Genes , Genômica/métodos , Neoplasias/genética , Oncogenes/genética , Linhagem Celular Tumoral , Mapeamento Cromossômico/métodos , Análise Citogenética , Genoma Humano/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
2.
Phytopathology ; 110(10): 1721-1726, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32915112

RESUMO

Stem rust is an important disease of cultivated oat (Avena sativa) caused by Puccinia graminis f. sp. avenae. In North America, host resistance is the primary strategy to control this disease and is conferred by a relatively small number of resistance genes. Pg2 is a widely deployed stem rust resistance gene that originates from cultivated oat. Oat breeders wish to develop cultivars with multiple Pg genes to slow the breakdown of single gene resistance, and often require DNA markers suited for marker-assisted selection. Our objectives were to (i) construct high density linkage maps for a major oat stem rust resistance gene using three biparental mapping populations, (ii) develop Kompetitive allele-specific PCR (KASP) assays for Pg2-linked single-nucleotide polymorphisms (SNPs), and (iii) test the prediction accuracy of those markers with a diverse panel of spring oat lines and cultivars. Genotyping-by-sequencing SNP markers linked to Pg2 were identified in an AC Morgan/CDC Morrison recombinant inbred line (RIL) population. Pg2-linked SNPs were then analyzed in an AC Morgan/RL815 F2 population and an AC Morgan/CDC Dancer RIL population. Linkage analysis identified a common location for Pg2 in all three populations on linkage group Mrg20 of the oat consensus genetic map. The most predictive markers were identified and converted to KASP assays for use in oat breeding programs. When used in combination, the KASP assays for the SNP loci avgbs2_126549.1.46 and avgbs_cluster_23819.1.27 were highly predictive of Pg2 status in panel of 54 oat breeding lines and cultivars.


Assuntos
Avena/genética , Basidiomycota , Mapeamento Cromossômico , Resistência à Doença/genética , Ligação Genética , Humanos , América do Norte , Doenças das Plantas , Polimorfismo de Nucleotídeo Único/genética
3.
Genome Res ; 30(10): 1434-1448, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32878977

RESUMO

The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the twenty-first century. We analyzed more than 4700 SARS-CoV-2 genomes and associated metadata retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus genome. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and more than 160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a rather uniform mutation occurrence along branches that could have implications for diagnostics and the design of future vaccines. Identification of the root of SARS-CoV-2 genomes is not without problems, owing to conflicting interpretations derived from either using the bat coronavirus genomes as an outgroup or relying on the sampling chronology of the SARS-CoV-2 genomes and TMRCA estimates; however, the overall scenario favors haplogroup A as the ancestral node. Phylogenetic analysis indicates a TMRCA for SARS-CoV-2 genomes dating to November 12, 2019, thus matching epidemiological records. Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to subclade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe. Multiple founder effect episodes, most likely associated with super-spreader hosts, might explain COVID-19 pandemic to a large extent.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Genoma Viral/genética , Pneumonia Viral/epidemiologia , Animais , Ásia/epidemiologia , Sequência de Bases/genética , Quirópteros/virologia , Mapeamento Cromossômico , Europa (Continente)/epidemiologia , Evolução Molecular , Variação Genética/genética , Humanos , Pandemias , Filogenia , Filogeografia , Homologia de Sequência do Ácido Nucleico
4.
Plant Mol Biol ; 104(1-2): 173-185, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32734417

RESUMO

KEY MESSAGE: A novel and major QTL for the effective tiller number was identified on chromosomal arm 1BL and validated in two genetic backgrounds The effective tiller number (ETN) substantially influences plant architecture and the wheat yield improvement. In this study, we constructed a genetic map of the 2SY (20828/SY95-71) recombinant inbred line population based on the Wheat 55K array as well as the simple sequence repeat (SSR) and Kompetitive Allele Specific PCR (KASP) markers. A comparison between the genetic and physical maps indicated the marker positions were consistent in the two maps. Additionally, we identified seven tillering-related quantitative trait locus (QTLs), including Qetn-sau-1B.1, which is a major QTL localized to a 6.17-cM interval flanked by markers AX-89635557 and AX-111544678 on chromosome 1BL. The Qetn-sau-1B.1 QTL was detected in eight environments and explained 12.12-55.71% of the phenotypic variance. Three genes associated with the ETN were detected in the physical interval of Qetn-sau-1B.1. We used a tightly linked KASP marker, KASP-AX-110129912, to further validate this QTL in two other populations with different genetic backgrounds. The results indicated that Qetn-sau-1B.1 significantly increased the ETN by up to 23.5%. The results of this study will be useful for the precise mapping and cloning of Qetn-sau-1B.1.


Assuntos
Cromossomos de Plantas , Locos de Características Quantitativas/genética , Triticum/genética , Bangladesh , Mapeamento Cromossômico , Marcadores Genéticos/genética , Genótipo , Repetições de Microssatélites , Anotação de Sequência Molecular , Fenótipo
5.
PLoS One ; 15(8): e0232806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785265

RESUMO

There is an increasing consumer demand for minimally processed, preservative free and microbiologically safe food. These factors, combined with risks of antibiotic resistance, have led to interest in bacteriocins produced by lactic acid bacteria (LAB) as natural food preservatives and as potential protein therapeutics. We previously reported the discovery of plantacyclin B21AG, a circular bacteriocin produced by Lactobacillus plantarum B21. Here, we describe the cloning and functional expression of the bacteriocin gene cluster in the probiotic Lactobacillus plantarum WCFS1. Genome sequencing demonstrated that the bacteriocin is encoded on a 20 kb native plasmid, designated as pB21AG01. Seven open reading frames (ORFs) putatively involved in bacteriocin production, secretion and immunity were cloned into an E. coli/Lactobacillus shuttle vector, pTRKH2. The resulting plasmid, pCycB21, was transformed into L. plantarum WCFS1. The cell free supernatants (CFS) of both B21 and WCFS1 (pCycB21) showed an antimicrobial activity of 800 AU/mL when tested against WCFS1 (pTRKH2) as the indicator strain, showing that functional expression of plantacyclin B21AG had been achieved. Real-time PCR analysis revealed that the relative copy number of pB21AG01 was 7.60 ± 0.79 in L. plantarum B21 whilst pCycB21 and pTRKH2 was 0.51 ± 0.05 and 25.19 ± 2.68 copies respectively in WCFS1. This indicates that the bacteriocin gene cluster is located on a highly stable low copy number plasmid pB21AG01 in L. plantarum B21. Inclusion of the native promoter for the bacteriocin operon from pB21AG01 results in similar killing activity being observed in both the wild type and recombinant hosts despite the lower copy number of pCycB21.


Assuntos
Bacteriocinas/genética , Microbiologia de Alimentos , Lactobacillus plantarum/genética , Probióticos , Mapeamento Cromossômico , Clonagem Molecular , Conservantes de Alimentos , Dosagem de Genes , Genes Bacterianos , Humanos , Família Multigênica , Plasmídeos/genética
6.
PLoS One ; 15(8): e0236285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841250

RESUMO

Characterizing meiotic recombination rates across the genomes of nonhuman primates is important for understanding the genetics of primate populations, performing genetic analyses of phenotypic variation and reconstructing the evolution of human recombination. Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primates in biomedical research. We constructed a high-resolution genetic map of the rhesus genome based on whole genome sequence data from Indian-origin rhesus macaques. The genetic markers used were approximately 18 million SNPs, with marker density 6.93 per kb across the autosomes. We report that the genome-wide recombination rate in rhesus macaques is significantly lower than rates observed in apes or humans, while the distribution of recombination across the macaque genome is more uniform. These observations provide new comparative information regarding the evolution of recombination in primates.


Assuntos
Evolução Molecular , Macaca mulatta/genética , Meiose/genética , Recombinação Genética , Animais , Mapeamento Cromossômico , Marcadores Genéticos , Variação Genética , Genoma , Humanos , Polimorfismo de Nucleotídeo Único , Especificidade da Espécie , Sequenciamento Completo do Genoma
7.
PLoS Negl Trop Dis ; 14(7): e0008330, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32609739

RESUMO

Sporotrichosis is a chronic subcutaneous mycosis caused by Sporothrix species, of which the main aetiological agents are S. brasiliensis, S. schenckii, and S. globosa. Infection occurs after a traumatic inoculation of Sporothrix propagules in mammals' skin and can follow either a classic route through traumatic inoculation by plant debris (e.g., S. schenckii and S. globosa) or an alternative route through zoonotic transmission from animals (e.g., S. brasiliensis). Epizootics followed by a zoonotic route occur in Brazil, with Rio de Janeiro as the epicenter of a recent cat-transmitted epidemic. DNA-based markers are needed to explore the epidemiology of these Sporothrix expansions using molecular methods. This paper reports the use of amplified-fragment-length polymorphisms (AFLP) to assess the degree of intraspecific variability among Sporothrix species. We used whole-genome sequences from Sporothrix species to generate 2,304 virtual AFLP fingerprints. In silico screening highlighted 6 primer pair combinations to be tested in vitro. The protocol was used to genotype 27 medically relevant Sporothrix. Based on the overall scored AFLP markers (97-137 fragments), the values of polymorphism information content (PIC = 0.2552-0.3113), marker index (MI = 0.002-0.0039), effective multiplex ratio (E = 17.8519-35.2222), resolving power (Rp = 33.6296-63.1852), discriminating power (D = 0.9291-0.9662), expected heterozygosity (H = 0.3003-0.3857), and mean heterozygosity (Havp = 0.0001) demonstrated the utility of these primer combinations for discriminating Sporothrix. AFLP markers revealed cryptic diversity in species previously thought to be the most prevalent clonal type, such as S. brasiliensis, responsible for cat-transmitted sporotrichosis, and S. globosa responsible for large sapronosis outbreaks in Asia. Three combinations (#3 EcoRI-FAM-GA/MseI-TT, #5 EcoRI-FAM-GA/MseI-AG, and #6 EcoRI-FAM-TA/MseI-AA) provide the best diversity indices and lowest error rates. These methods make it easier to track routes of disease transmission during epizooties and zoonosis, and our DNA fingerprint assay can be further transferred between laboratories to give insights into the ecology and evolution of pathogenic Sporothrix species and to inform management and mitigation strategies to tackle the advance of sporotrichosis.


Assuntos
Doenças do Gato/epidemiologia , Mapeamento Cromossômico , Sporothrix/classificação , Esporotricose/epidemiologia , Esporotricose/veterinária , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Animais , Brasil/epidemiologia , Doenças do Gato/microbiologia , Gatos , Surtos de Doenças , Genótipo , Epidemiologia Molecular , Sporothrix/isolamento & purificação , Esporotricose/microbiologia
8.
Plant Dis ; 104(9): 2411-2417, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32658634

RESUMO

Chinese wheat landrace Youbailan has excellent resistance to powdery mildew caused by Blumeria graminis f. sp. tritici. In the present study, genetic analysis indicated that a recessive gene, tentatively designated pmYBL, was responsible for the powdery mildew resistance of Youbailan. pmYBL was located in the 695-to-715-Mb genomic region of chromosome 7BL, with 19 gene-linked single-nucleotide polymorphism (SNP) markers. It was flanked by SNP1-12 and SNP1-2 with genetic distances of 0.6 and 1.8 centimorgans, respectively. The disease reaction patterns of Youbailan and four cultivars (lines) carrying the powdery mildew (Pm) genes located on chromosome arm 7BL indicated that pmYBL may be allelic or closely linked to these genes. All of the SNP markers linked to pmYBL were diagnostic, indicating that these markers will be useful for pyramiding pmYBL using marker-assisted selection.


Assuntos
Resistência à Doença/genética , Triticum/genética , Mapeamento Cromossômico , Genes de Plantas , Humanos , Doenças das Plantas
9.
PLoS One ; 15(7): e0235434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649700

RESUMO

The genetic diversity of North American soybean cultivars has been largely influenced by a small number of ancestors. High yielding breeding lines that possess exotic pedigrees have been developed, but identifying beneficial exotic alleles has been difficult as a result of complex interactions of yield alleles with genetic backgrounds and environments as well as the highly quantitative nature of yield. PI 416937 has been utilized in the development of many high yielding lines that have been entered into the USDA Southern States Uniform Tests over the past ~20 years. The primary goal of this research was to identify genomic regions under breeding selection from PI 416937 and introduce a methodology for identifying and potentially utilizing beneficial diversity from lines prevalent in the ancestry of elite cultivars. Utilizing SoySNP50K Infinium BeadChips, 52 high yielding PI 416937-derived lines as well as their parents were genotyped to identify PI 416937 alleles under breeding selection. Nine genomic regions across three chromosomes and 17 genomic regions across seven chromosomes were identified where PI 416937 alleles were under positive or negative selection. Minimal significant associations between PI 416937 alleles and yield were observed in replicated yield trials of five RIL populations, highlighting the difficulty of consistently detecting yield associations.


Assuntos
Cruzamento , Variação Genética/genética , Soja/genética , Alelos , Mapeamento Cromossômico , Cromossomos de Plantas , Genoma de Planta/genética , Genômica , Genótipo , Humanos , Locos de Características Quantitativas/genética , Sementes/genética , Sementes/crescimento & desenvolvimento , Soja/crescimento & desenvolvimento , Estados Unidos
10.
Nat Commun ; 11(1): 3294, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620744

RESUMO

Systemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage multiple tissues. Genome-wide association studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are largely unknown. We generated high-resolution spatial maps of SLE variant accessibility and gene connectivity in human follicular helper T cells (TFH), a cell type required for anti-nuclear antibodies characteristic of SLE. Of the ~400 potential regulatory variants identified, 90% exhibit spatial proximity to genes distant in the 1D genome sequence, including variants that loop to regulate the canonical TFH genes BCL6 and CXCR5 as confirmed by genome editing. SLE 'variant-to-gene' maps also implicate genes with no known role in TFH/SLE disease biology, including the kinases HIPK1 and MINK1. Targeting these kinases in TFH inhibits production of IL-21, a cytokine crucial for class-switched B cell antibodies. These studies offer mechanistic insight into the SLE-associated regulatory architecture of the human genome.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Linfócitos T Auxiliares-Indutores/metabolismo , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Células Cultivadas , Mapeamento Cromossômico/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Células Jurkat , Lúpus Eritematoso Sistêmico/imunologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Interferência de RNA , Receptores CXCR5/genética , Linfócitos T Auxiliares-Indutores/imunologia
11.
Nat Commun ; 11(1): 3613, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680994

RESUMO

Common fragile sites (CFSs) are regions susceptible to replication stress and are hotspots for chromosomal instability in cancer. Several features were suggested to underlie CFS instability, however, these features are prevalent across the genome. Therefore, the molecular mechanisms underlying CFS instability remain unclear. Here, we explore the transcriptional profile and DNA replication timing (RT) under mild replication stress in the context of the 3D genome organization. The results reveal a fragility signature, comprised of a TAD boundary overlapping a highly transcribed large gene with APH-induced RT-delay. This signature enables precise mapping of core fragility regions in known CFSs and identification of novel fragile sites. CFS stability may be compromised by incomplete DNA replication and repair in TAD boundaries core fragility regions leading to genomic instability. The identified fragility signature will allow for a more comprehensive mapping of CFSs and pave the way for investigating mechanisms promoting genomic instability in cancer.


Assuntos
Sítios Frágeis do Cromossomo/genética , Período de Replicação do DNA/genética , Genoma Humano , Instabilidade Genômica , Afidicolina/farmacologia , Linhagem Celular , Sequenciamento de Cromatina por Imunoprecipitação , Mapeamento Cromossômico/métodos , DNA/química , Período de Replicação do DNA/efeitos dos fármacos , Fibroblastos , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/genética , Conformação de Ácido Nucleico , Sensibilidade e Especificidade , Transcrição Genética/efeitos dos fármacos
12.
PLoS One ; 15(7): e0235756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702059

RESUMO

Genome-wide association studies (GWAS) have routinely detected human quantitative trait loci (QTLs) for complex traits. Viewing that most GWAS single nucleotide polymorphisms (SNPs) are found in non-coding regions unrelated to the physiology of a polygenic trait of interest, a vital question to answer is whether or not any of these SNPs can functionally alter the phenotype with which it is associated. The study of blood pressure (BP) is a case in point. Conserved mechanisms in controlling BP by modularity is now unifying differing mammalian orders in that understanding mechanisms in rodents is tantamount to revealing the same in humans, while overcoming experimental limitations imposed by human studies. As a proof of principle, we used BP QTLs from Dahl salt-sensitive rats (DSS) as substitutes to capture distinct human functional orthologs. 3 DSS BP QTLs are located into distinct genome regions and correspond to several human GWAS genes. Each of the QTLs independently exerted a major impact on BP in vivo. BP was functionally changed by normotensive alleles from each of these QTLs, and yet, the human GWAS SNPs do not exist in the rat. They cannot be responsible for physiological alterations in BP caused by these QTLs. These SNPs are genome emblems for QTLs nearby, rather than being QTLs per se, since they only emerged during primate evolution after BP-regulating mechanisms have been established. We then identified specific mutated coding domains that are conserved between rodents and humans and that may implicate different steps of a common pathway or separate pathways.


Assuntos
Pressão Sanguínea/genética , Estudo de Associação Genômica Ampla , Hipertensão/genética , Hipertensão/prevenção & controle , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Animais , Determinação da Pressão Arterial , Mapeamento Cromossômico , Humanos , Masculino , Fenótipo , Ratos , Ratos Endogâmicos Dahl
13.
Nat Commun ; 11(1): 3676, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32719321

RESUMO

The genomes of non-bilaterian metazoans are key to understanding the molecular basis of early animal evolution. However, a full comprehension of how animal-specific traits, such as nervous systems, arose is hindered by the scarcity and fragmented nature of genomes from key taxa, such as Porifera. Ephydatia muelleri is a freshwater sponge found across the northern hemisphere. Here, we present its 326 Mb genome, assembled to high contiguity (N50: 9.88 Mb) with 23 chromosomes on 24 scaffolds. Our analyses reveal a metazoan-typical genome architecture, with highly shared synteny across Metazoa, and suggest that adaptation to the extreme temperatures and conditions found in freshwater often involves gene duplication. The pancontinental distribution and ready laboratory culture of E. muelleri make this a highly practical model system which, with RNAseq, DNA methylation and bacterial amplicon data spanning its development and range, allows exploration of genomic changes both within sponges and in early animal evolution.


Assuntos
Mapeamento Cromossômico , Cromossomos/genética , Evolução Molecular , Poríferos/genética , Adaptação Fisiológica/genética , Animais , Epigênese Genética , Água Doce , Regulação da Expressão Gênica no Desenvolvimento , Anotação de Sequência Molecular , Filogenia , Poríferos/crescimento & desenvolvimento , RNA-Seq , Análise de Sequência de DNA , Sintenia
14.
PLoS One ; 15(7): e0236273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722687

RESUMO

Creating a homologous restorer line for Ogura cytoplasmic male sterility (Ogu-CMS) in Brassica napus is meaningful for the wider application of Ogu-CMS system in rapeseed production. Previously, an independent development of a new Ogu-CMS restorer line (CLR650) was reported locally from crossing between Raphanobrassica (AACCRR, 2n = 56) and B. napus and a new version of Ogu CMS lines CLR6430 derived from CLR650 was characterized in this study. The results showed that the fertility restoration gene in CLR6430 presented a distorted segregation in different segregating populations. However, the majority of somatic cells from roots had a regular chromosome number (2n = 38) and no radish signal covered a whole chromosome was detected using GISH. Thirty-two specific markers derived from the introgressed radish fragments were developed based on the re-sequencing results. Unique radish insertions and differences between CLR6430 and R2000 were also identified through both radish-derived markers and PCR product sequences. Further investigations on the genetic behaviors, interactions between the fertility restoration and other traits and specific molecular markers to the introgression in CLR6430 were also conducted in this study. These results should provide the evidence of nucleotide differences between CLR6430 and R2000, and the specific markers will be helpful for breeding new Ogura restore lines in future.


Assuntos
Brassica napus/genética , Marcadores Genéticos/genética , Infertilidade das Plantas/genética , Brassica rapa/genética , Mapeamento Cromossômico , Cromossomos de Plantas , DNA de Plantas/química , DNA de Plantas/isolamento & purificação , DNA de Plantas/metabolismo , Repetições de Microssatélites/genética , Raphanus/genética
15.
PLoS One ; 15(6): e0233377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502155

RESUMO

The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal and facial development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL's peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.


Assuntos
Desenvolvimento Ósseo/genética , Ossos Faciais/anatomia & histologia , Desenvolvimento Maxilofacial/genética , Alelos , Animais , Osso e Ossos/anatomia & histologia , Mapeamento Cromossômico/métodos , Camundongos de Cruzamento Colaborativo/genética , Face/anatomia & histologia , Feminino , Variação Genética/genética , Genótipo , Masculino , Camundongos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
16.
PLoS One ; 15(6): e0234052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502173

RESUMO

Like other crop species, barley, the fourth most important crop worldwide, suffers from the genetic bottleneck effect, where further improvements in performance through classical breeding methods become difficult. Therefore, indirect selection methods are of great interest. Here, genomic prediction (GP) based on 33,005 SNP markers and, alternatively, metabolic prediction (MP) based on 128 metabolites with sampling at two different time points in one year, were applied to predict multi-year agronomic traits in the nested association mapping (NAM) population HEB-25. We found prediction abilities of up to 0.93 for plant height with SNP markers and of up to 0.61 for flowering time with metabolites. Interestingly, prediction abilities in GP increased after reducing the number of incorporated SNP markers. The estimated effects of GP and MP were highly concordant, indicating MP as an interesting alternative to GP, being able to reflect a stable genotype-specific metabolite profile. In MP, sampling at an early developmental stage outperformed sampling at a later stage. The results confirm the value of GP for future breeding. With MP, an interesting alternative was also applied successfully. However, based on our results, usage of MP alone cannot be recommended in barley. Nevertheless, MP can assist in unravelling physiological pathways for the expression of agronomically important traits.


Assuntos
Genoma de Planta , Hordeum/genética , Metaboloma , Teorema de Bayes , Mapeamento Cromossômico , Genótipo , Hordeum/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único
17.
PLoS One ; 15(6): e0234335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516348

RESUMO

Shoot fly (Atherigona naqvii) is one of the major insects affecting spring maize in North India and can cause yield loss up to 60 per cent. The genetics of insect resistance is complex as influenced by genotypic background, insect population and climatic conditions. Therefore, quantitative trait loci (QTL) mapping is a highly effective approach for studying genetically complex forms of insect resistance. The objective of the present study was to dissect the genetic basis of resistance and identification of genomic regions associated with shoot fly resistance. A total of 107 F2 population derived from the cross CM143 (resistant) x CM144 (susceptible) was genotyped with 120 SSR markers. Phenotypic data were recorded on replicated F2:3 progenies for various component traits imparting resistance to shoot fly at different time intervals. Resistance to shoot fly was observed to be under polygenic control as evidenced by the identification of 19 putative QTLs governed by overdominance to partial dominance and additive gene actions. The major QTLs conditioning shoot fly resistance viz., qDH9.1 (deadheart) and qEC9.1 (oviposition) explaining 15.03 and 18.89 per cent phenotypic variance, respectively were colocalized on chromosome 9. These QTLs are syntenic to regions of chromosome 10 of sorghum which were also accounted for deadheart and oviposition suggesting that the same gene block may be responsible for shoot fly resistance. The candidate genes such as cysteine protease, subtilisin-chymotrypsin inhibitor, cytochrome P450 involved in synthesis of alleochemicals, receptor kinases, glossy15 and ubiquitin-proteasome degradation pathway were identified within the predicted QTL regions. This is the first reported mapping of QTLs conferring resistance to shoot fly in maize, and the markers identified here will be a valuable resource for developing elite maize cultivars with resistance to shoot fly.


Assuntos
Resistência à Doença/genética , Sorghum/genética , Zea mays/genética , Animais , Mapeamento Cromossômico/métodos , Grão Comestível/genética , Genômica/métodos , Genótipo , Índia , Insetos , Repetições de Microssatélites/genética , Controle Biológico de Vetores/métodos , Fenótipo , Doenças das Plantas/genética , Locos de Características Quantitativas/genética
18.
Mol Cell ; 79(3): 521-534.e15, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32592681

RESUMO

Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.


Assuntos
Cromatina/metabolismo , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Genoma Humano , Neurogênese/genética , Regiões Promotoras Genéticas , Adulto , Linhagem Celular , Cérebro/citologia , Cérebro/crescimento & desenvolvimento , Cérebro/metabolismo , Cromatina/ultraestrutura , Mapeamento Cromossômico , Feto , Histonas/genética , Histonas/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Neurônios/citologia , Neurônios/metabolismo , Lobo Temporal/citologia , Lobo Temporal/crescimento & desenvolvimento , Lobo Temporal/metabolismo , Fatores de Transcrição/classificação , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
PLoS One ; 15(6): e0234411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511257

RESUMO

The AINTEGUMENTA-like (AIL) proteins, which belong to the AP2 family, play important roles in regulating the growth and development of plant organs. The AIL family has not yet been comprehensively studied in rapeseed (Brassica napus), an allotetraploid and model organism for the study of polyploid evolution. In the present study, 99 AIL family genes were identified and characterized from B. rapa, B. oleracea, B. napus, B. juncea, and B. nigra using a comprehensive genome-wide study, including analyses of phylogeny, gene structure, chromosomal localization, and expression pattern. Using a phylogenetic analysis, the AIL genes were divided into eight groups, which were closely related to the eight AtAIL genes, and which shared highly conserved structural features within the same subfamily. The non-synonymous/synonymous substitution ratios of the paralogs and orthologs were less than 1, suggesting that the AIL genes mainly experienced purifying selection during evolution. In addition, the RNA sequencing data and qRT-PCR analysis revealed that the B. napus AIL genes exhibited organ- and developmental stage-specific expression patterns. Certain genes were highly expressed in the developing seeds (BnaAIL1, BnaAIL2, BnaAIL5, and BnaAIL6), the roots (BnaANT, BnaAIL5, and BnaAIL6), and the stem (BnaAIL7B). Our results provide valuable information for further functional analysis of the AIL family in B. napus and related Brassica species.


Assuntos
Brassica napus/genética , Brassica/genética , Genes de Plantas , Sequência de Aminoácidos , Proteínas de Arabidopsis/genética , Brassica/crescimento & desenvolvimento , Brassica napus/crescimento & desenvolvimento , Mapeamento Cromossômico , Sequência Conservada , Duplicação Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Proteínas de Homeodomínio/genética , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Sintenia
20.
PLoS Comput Biol ; 16(6): e1007770, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32516306

RESUMO

A longstanding goal of regulatory genetics is to understand how variants in genome sequences lead to changes in gene expression. Here we present a method named Bayesian Annotation Guided eQTL Analysis (BAGEA), a variational Bayes framework to model cis-eQTLs using directed and undirected genomic annotations. We used BAGEA to integrate directed genomic annotations with eQTL summary statistics from tissues of various origins. This analysis revealed epigenetic marks that are relevant for gene expression in different tissues and cell types. We estimated the predictive power of the models that were fitted based on directed genomic annotations. This analysis showed that, depending on the underlying eQTL data used, the directed genomic annotations could predict up to 1.5% of the variance observed in the expression of genes with top nominal eQTL association p-values < 10-7. For genes with estimated effect sizes in the top 25% quantile, up to 5% of the expression variance could be predicted. Based on our results, we recommend the use of BAGEA for the analysis of cis-eQTL data to reveal annotations relevant to expression biology.


Assuntos
Biologia Computacional/métodos , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Algoritmos , Teorema de Bayes , Mapeamento Cromossômico , DNA/análise , Epigênese Genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genoma Humano , Genômica , Genótipo , Humanos , Anotação de Sequência Molecular , Monócitos/metabolismo , Software
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