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1.
Gene ; 720: 144078, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473321

RESUMO

Short tandem repeats (STRs) are a widely utilized tool in forensic applications, the latter of which range from human identification and paternity testing to population analysis. The GlobalFiler STR loci, which includes 21 autosomal STRS, were analyzed in the Chechen subpopulation of Jordan. Whole blood samples were withdrawn from 159 Jordanian Chechen individuals, and genomic DNA was extracted from each sample. The GlobalFiler™ kit PCR Amplification Kit amplified and analyzed the STR loci on the 3130xl Genetic Analyzer using GeneMapper ID-X software. The combined match probability for the 21 autosomal STR loci was calculated to be 1.06 × 10-24, a number that is highly discriminatory and informative. The SE33 (0.983) and TPOX (0.806) loci exhibited the highest and lowest powers of discrimination, respectively. Conclusively, the current study indicates that the GlobalFiler loci have a high utility in the Jordanian Chechen population, possibly paving the way for the future establishment of a reference population database in Jordan.


Assuntos
DNA/análise , DNA/genética , Grupos Étnicos/genética , Genética Forense/estatística & dados numéricos , Genética Populacional , Repetições de Microssatélites , Polimorfismo Genético , Impressões Digitais de DNA , Feminino , Frequência do Gene , Loci Gênicos , Humanos , Masculino
2.
BMC Plant Biol ; 19(1): 324, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324149

RESUMO

BACKGROUND: Leaf shape development research is important because leaf shapes such as moderate curling can help to improve light energy utilization efficiency. Leaf growth and development includes initiation of the leaf primordia and polar differentiation of the proximal-distal, adaxial-abaxial, and centrolateral axes. Changes in leaf adaxial-abaxial polarity formation, auxin synthesis and signaling pathways, and development of sclerenchyma and cuticle can cause abnormal leaf shapes such as up-curling leaf. Although many genes related to leaf shape development have been reported, the detailed mechanism of leaf development is still unclear. Here, we report an up-curling leaf mutant plant from our Brassica napus germplasm. We studied its inheritance, mapped the up-curling leaf locus BnUC1, built near-isogenic lines for the Bnuc1 mutant, and evaluated the effect of the dominant leaf curl locus on leaf photosynthetic efficiency and agronomic traits. RESULTS: The up-curling trait was controlled by one dominant locus in a progeny population derived from NJAU5734 and Zhongshuang 11 (ZS11). This BnUC1 locus was mapped in an interval of 2732.549 kb on the A05 chromosome of B. napus using Illumina Brassica 60 K Bead Chip Array. To fine map BnUC1, we designed 201 simple sequence repeat (SSR) primers covering the mapping interval. Among them, 16 polymorphic primers that narrowed the mapping interval to 54.8 kb were detected using a BC6F2 family population with 654 individuals. We found six annotated genes in the mapping interval using the B. napus reference genome, including BnaA05g18250D and BnaA05g18290D, which bioinformatics and gene expression analyses predicted may be responsible for leaf up-curling. The up-curling leaf trait had negative effects on the agronomic traits of 30 randomly selected individuals from the BC6F2 population. The near-isogenic line of the up-curling leaf (ZS11-UC1) was constructed to evaluate the effect of BnUC1 on photosynthetic efficiency. The results indicated that the up-curling leaf trait locus was beneficial to improve the photosynthetic efficiency. CONCLUSIONS: An up-curling leaf mutant Bnuc1 was controlled by one dominant locus BnUC1. This locus had positive effects on photosynthetic efficiency, negative effects on some agronomic traits, and may help to increase planting density in B. napus.


Assuntos
Brassica napus/genética , Genes de Plantas/genética , Folhas de Planta/anatomia & histologia , Brassica napus/anatomia & histologia , Clorofila/metabolismo , Mapeamento Cromossômico , Genes de Plantas/fisiologia , Loci Gênicos , Mutação , Fotossíntese , Reação em Cadeia da Polimerase em Tempo Real
3.
Gene ; 715: 143991, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31357023

RESUMO

BACKGROUND: Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. OBJECTIVE: This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. METHODS: This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). RESULTS: Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44-3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. CONCLUSIONS: We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus.


Assuntos
Asma/genética , Cromossomos Humanos Par 17/genética , Predisposição Genética para Doença , Herpesvirus Humano 3 , Polimorfismo de Nucleotídeo Único , Infecção pelo Vírus da Varicela-Zoster/genética , Asma/virologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Masculino
4.
BMC Plant Biol ; 19(1): 332, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357930

RESUMO

BACKGROUND: Good establishment is important for rapid leaf area development in wheat crops. Poor establishment results in fewer, later-emerging plants, reduced leaf area and tiller number. In addition, poorly established crops suffer from increased soil moisture loss through evaporation and greater competition from weeds while fewer spikes are produced which can reduce grain yield. By protecting the emerging first leaf, the coleoptile is critical for achieving good establishment, and its length and interaction with soil physical properties determine the ability of a cultivar to emerge from depth. RESULTS: Here we characterise a locus on chromosome 1AS, that increases coleoptile length in wheat, which we designate as Lcol-A1. We identified Lcol-A1 by bulked-segregant analysis and used a Halberd-derived population to fine map the gene to a 2 cM region, equivalent to 7 Mb on the IWGSC genome reference sequence of Chinese Spring (RefSeqv1.0). By sowing recently released cultivars and near-isogenic lines in the field at both conventional and deep sowing depths, we confirmed that Locl-A1 was associated with increased emergence from depth in the presence and absence of conventional dwarfing genes. Flanking markers IWB58229 and IWA710 were developed to assist breeders to select for long coleoptile wheats. CONCLUSIONS: Increased coleoptile length is sought in many global wheat production areas to improve crop emergence. The identification of the gene Lcol-A1, together with tools to allow wheat breeders to track the gene, will enable improvements to be made for this important trait.


Assuntos
Cotilédone/crescimento & desenvolvimento , Genes de Plantas/fisiologia , Triticum/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Genes de Plantas/genética , Estudos de Associação Genética , Loci Gênicos , Folhas de Planta/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa Herdável , Triticum/crescimento & desenvolvimento
5.
BMC Bioinformatics ; 20(1): 371, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266441

RESUMO

BACKGROUND: The falling cost of next-generation sequencing technology has allowed deep sequencing across related species and of individuals within species. Whole genome assemblies from these data remain high time- and resource-consuming computational tasks, particularly if best solutions are sought using different assembly strategies and parameter sets. However, in many cases, the underlying research questions are not genome-wide but rather target specific genes or sets of genes. We describe a novel assembly tool, SRAssembler, that efficiently assembles only contigs containing potential homologs of a gene or protein query, thus enabling gene-specific genome studies over large numbers of short read samples. RESULTS: We demonstrate the functionality of SRAssembler with examples largely drawn from plant genomics. The workflow implements a recursive strategy by which relevant reads are successively pulled from the input sets based on overlapping significant matches, resulting in virtual chromosome walking. The typical workflow behavior is illustrated with assembly of simulated reads. Applications to real data show that SRAssembler produces homologous contigs of equivalent quality to whole genome assemblies. Settings can be chosen to not only assemble presumed orthologs but also paralogous gene loci in distinct contigs. A key application is assembly of the same locus in many individuals from population genome data, which provides assessment of structural variation beyond what can be inferred from read mapping to a reference genome alone. SRAssembler can be used on modest computing resources or used in parallel on high performance computing clusters (most easily by invoking a dedicated Singularity image). CONCLUSIONS: SRAssembler offers an efficient tool to complement whole genome assembly software. It can be used to solve gene-specific research questions based on large genomic read samples from multiple sources and would be an expedient choice when whole genome assembly from the reads is either not feasible, too costly, or unnecessary. The program can also aid decision making on the depth of sequencing in an ongoing novel genome sequencing project or with respect to ultimate whole genome assembly strategies.


Assuntos
Genômica/métodos , Software , Arabidopsis/genética , Loci Gênicos , Genoma de Planta , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA
6.
Nat Commun ; 10(1): 3009, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285442

RESUMO

Quantitative genetics theory predicts that X-chromosome dosage compensation (DC) will have a detectable effect on the amount of genetic and therefore phenotypic trait variances at associated loci in males and females. Here, we systematically examine the role of DC in humans in 20 complex traits in a sample of more than 450,000 individuals from the UK Biobank and 1600 gene expression traits from a sample of 2000 individuals as well as across-tissue gene expression from the GTEx resource. We find approximately twice as much X-linked genetic variation across the UK Biobank traits in males (mean h2SNP = 0.63%) compared to females (mean h2SNP = 0.30%), confirming the predicted DC effect. Our DC estimates for complex traits and gene expression are consistent with a small proportion of genes escaping X-inactivation in a trait- and tissue-dependent manner. Finally, we highlight examples of biologically relevant X-linked heterogeneity between the sexes that bias DC estimates if unaccounted for.


Assuntos
Genes Ligados ao Cromossomo X/genética , Loci Gênicos/genética , Variação Genética/genética , Herança Multifatorial/genética , Inativação do Cromossomo X/genética , Conjuntos de Dados como Assunto , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Modelos Genéticos , Fenótipo , Fatores Sexuais
7.
Hum Genet ; 138(10): 1077-1090, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31172260

RESUMO

High hyperopia is a common and severe form of refractive error. Genetic factors play important roles in the development of high hyperopia but the exact gene responsible for this condition is mostly unknown. We identified a large Chinese family with autosomal dominant high hyperopia. A genome-wide linkage scan mapped the high hyperopia to chromosome 11p12-q13.3, with maximum log of the odds scores of 4.68 at theta = 0 for D11S987. Parallel whole-exome sequencing detected a novel c.3377delG (p.Gly1126Valfs*31) heterozygous mutation in the MYRF gene within the linkage interval. Whole-exome sequencing in other 121 probands with high hyperopia identified additional novel mutations in MYRF within two other families: a de novo c.3274_3275delAG (p.Leu1093Profs*22) heterozygous mutation and a c.3194+2T>C heterozygous mutation. All three mutations are located in the C-terminal region of MYRF and are predicted to result in truncation of that portion. Two patients from two of the three families developed angle-closure glaucoma. These three mutations were present in neither the ExAC database nor our in-house whole-exome sequencing data from 3280 individuals. No other truncation mutations in MYRF were detected in the 3280 individuals. Knockdown of myrf resulted in small eye size in zebrafish. These evidence all support that truncation mutations in the C-terminal region of MYRF are responsible for autosomal dominant high hyperopia in these families. Our results may provide useful clues for further understanding the functional role of the C-terminal region of this critical myelin regulatory factor, as well as the molecular pathogenesis of high hyperopia and its associated angle-closure glaucoma.


Assuntos
Cromossomos Humanos Par 11 , Oftalmopatias Hereditárias/genética , Genes Dominantes , Estudos de Associação Genética , Predisposição Genética para Doença , Hiperopia/genética , Proteínas de Membrana/genética , Mutação , Fatores de Transcrição/genética , Animais , Mapeamento Cromossômico , Análise Mutacional de DNA , Oftalmopatias Hereditárias/diagnóstico , Feminino , Angiofluoresceinografia , Técnicas de Inativação de Genes , Loci Gênicos , Humanos , Hiperopia/diagnóstico , Escore Lod , Masculino , Linhagem , Fenótipo , Peixe-Zebra
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(6): 676-681, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31238618

RESUMO

Objective: To study the molecular-epidemiological characteristics of Brucella species isolated from different countries, using the multiple locus tandem-repeat (MLVA) analysis. Methods: Eleven variable-number tandem-repeat (VNTR) loci were selected. VNTR strains of Brucella isolated from 48 different countries in 1953-2013, were analyzed by using the BioNumerics software. Unweighted Paired Arithmetic Average method was used to cluster and draw phylogenetic tree as well as the minimum spannin. Results: The evolutionary relationship of Brucella phylogenetic tree was consistent with the classical biological typing method. However, the Brucella suis biovar 5 strains were different from the other Brucella suis biovars 1, 2, 3 and 4. Brucella ceti strains were divided into two parts and different from each other. Worldwide epidemics of brucellosis were emerged from 2005 to 2008 under the MLVA11 Orsay analysis. China has been a brucellosis-prone regions, with Brucella melitensis as the main epidemic Brucella species, followed by Brucella abortus. Brucella suis was mainly identified in the southern provinces, but Brucella canis was mainly found in dogs. No human cases were found. Conclusion: Molecular-epidemiological characteristics of the Brucella strains were related to factors as time, region and hosts of isolation, which are important to setting up prevention and control programs on brucellosis.


Assuntos
Brucella/genética , Brucella/isolamento & purificação , Brucelose/epidemiologia , Tipagem de Sequências Multilocus/métodos , Brucella/classificação , Brucelose/diagnóstico , Brucelose/microbiologia , China , DNA Bacteriano/genética , Loci Gênicos , Genótipo , Humanos , Repetições de Microssatélites/genética , Repetições Minissatélites/genética , Epidemiologia Molecular , Filogenia , Sequências de Repetição em Tandem
9.
Croat Med J ; 60(3): 191-200, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31187946

RESUMO

AIM: To determine allele frequencies and forensic statistics of 22 autosomal short tandem repeat loci in Chinese Mongolian population. METHODS: Blood specimens were collected from 134 unrelated healthy Mongolian individuals, and 22 short tandem repeat loci were co-amplified and genotyped. Allele frequencies and forensic parameters were calculated, and population genetic differences were analyzed among Mongolian population and other eight Chinese populations: Northern Han, Guangdong Han, Chengdu Han, Xinjiang Hui, Xinjiang Uygur, Hainan Li, Qinghai Tibetan, and Hainan Han. RESULTS: All the loci were in the Hardy-Weinberg equilibrium, and after Bonferroni correction there was no linkage disequilibrium between them. The allele frequencies of these 22 loci were between 0.0037 and 0.3657. This panel had high discriminating power and genetic polymorphism in the Mongolian population, with combined power of discrimination of 0.999999999999999999999999998399 and combined probability of exclusion of 0.9999999999566925. Structure analysis showed no evidence that these nine Chinese populations had different component distribution. However, genetic distance analysis showed significant differences among them (P<0.05). CONCLUSION: The combined application of these 22 loci could be useful for forensic purposes in the Mongolian population. Mongolian population had smaller genetic distances from the populations in northern China (Northern Han, Xinjiang Uygur, and Xinjiang Hui) than from the populations in Hainan province (Hainan Han and Hainan Li populations).


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Repetições de Microssatélites , Polimorfismo Genético , China , Feminino , Genética Forense , Frequência do Gene , Loci Gênicos , Testes Genéticos , Genética Populacional , Genótipo , Humanos , Masculino
10.
Nature ; 571(7763): 107-111, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31217582

RESUMO

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes.


Assuntos
Diarreia/congênito , Diarreia/genética , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes , Intestinos/fisiologia , Deleção de Sequência/genética , Animais , Cromossomos Humanos Par 16/genética , Modelos Animais de Doenças , Feminino , Genes Reporter , Loci Gênicos/genética , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Linhagem , Fenótipo , Ativação Transcricional , Transcriptoma/genética , Transgenes/genética
11.
Hum Genet ; 138(10): 1105-1115, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31230195

RESUMO

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (~ 45%) that manifests before 30 years of age. The genetic locus containing COL4A1 (13q33-34) has been implicated in vesicoureteral reflux (VUR), but mutations in COL4A1 have not been reported in CAKUT. We hypothesized that COL4A1 mutations cause CAKUT in humans. We performed whole exome sequencing (WES) in 550 families with CAKUT. As negative control cohorts we used WES sequencing data from patients with nephronophthisis (NPHP) with no genetic cause identified (n = 257) and with nephrotic syndrome (NS) due to monogenic causes (n = 100). We identified a not previously reported heterozygous missense variant in COL4A1 in three siblings with isolated VUR. When examining 549 families with CAKUT, we identified nine additional different heterozygous missense mutations in COL4A1 in 11 individuals from 11 unrelated families with CAKUT, while no COL4A1 mutations were identified in a control cohort with NPHP and only one in the cohort with NS. Most individuals (12/14) had isolated CAKUT with no extrarenal features. The predominant phenotype was VUR (9/14). There were no clinical features of the COL4A1-related disorders (e.g., HANAC syndrome, porencephaly, tortuosity of retinal arteries). Whereas COL4A1-related disorders are typically caused by glycine substitutions in the collagenous domain (84.4% of variants), only one variant in our cohort is a glycine substitution within the collagenous domain (1/10). We identified heterozygous COL4A1 mutations as a potential novel autosomal dominant cause of CAKUT that is allelic to the established COL4A1-related disorders and predominantly caused by non-glycine substitutions.


Assuntos
Colágeno Tipo IV/genética , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/genética , Rim/anormalidades , Mutação , Fenótipo , Sistema Urinário/anormalidades , Alelos , Substituição de Aminoácidos , Biologia Computacional/métodos , Análise Mutacional de DNA , Bases de Dados Genéticas , Evolução Molecular , Feminino , Estudos de Associação Genética , Loci Gênicos , Genômica/métodos , Heterozigoto , Humanos , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Masculino , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Navegador , Sequenciamento Completo do Exoma
12.
Nat Commun ; 10(1): 2043, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053724

RESUMO

Unlike proteins, glycan chains are not directly encoded by DNA, but by the specificity of the enzymes that assemble them. Theoretical calculations have proposed an astronomical number of possible isomers (> 1012 hexasaccharides) but the actual diversity of glycan structures in nature is not known. Bacteria of the Bacteroidetes phylum are considered primary degraders of polysaccharides and they are found in all ecosystems investigated. In Bacteroidetes genomes, carbohydrate-degrading enzymes (CAZymes) are arranged in gene clusters termed polysaccharide utilization loci (PULs). The depolymerization of a given complex glycan by Bacteroidetes PULs requires bespoke enzymes; conversely, the enzyme composition in PULs can provide information on the structure of the targeted glycans. Here we group the 13,537 PULs encoded by 964 Bacteroidetes genomes according to their CAZyme composition. We find that collectively Bacteroidetes have elaborated a few thousand enzyme combinations for glycan breakdown, suggesting a global estimate of diversity of glycan structures much smaller than the theoretical one.


Assuntos
Proteínas de Bactérias/genética , Bacteroidetes/genética , Enzimas/genética , Genoma Bacteriano/genética , Polissacarídeos/metabolismo , Proteínas de Bactérias/metabolismo , Bacteroidetes/metabolismo , Enzimas/metabolismo , Loci Gênicos , Isomerismo , Polissacarídeos/química
13.
BMC Plant Biol ; 19(1): 200, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092192

RESUMO

BACKGROUND: Rice (Oryza sativa L.) is a staple food crop worldwide. Its yield and quality are affected by its tillering pattern and spikelet development. Although many genes involved in the vegetative and reproductive development of rice have been characterized in previous studies, the genetic mechanisms that control axillary tillering, spikelet development, and panicle exsertion remain incompletely understood. RESULTS: Here, we characterized a novel rice recombinant inbred line (RIL), panicle exsertion defect and aberrant spikelet (pds). It was derived from a cross between two indica varieties, S142 and 430. Intriguingly, no abnormal phenotypes were observed in the parents of pds. This RIL exhibited sheathed panicles at heading stage. Still, a small number of tillers in pds plants were fully exserted from the flag leaves. Elongated sterile lemmas and rudimentary glumes (occurred occasionally) were observed in the spikelets of the exserted panicles and were transformed into palea/lemma-like structures. Furthermore, more interestingly, tillers occasionally grew from the axils of the elongated rudimentary glumes. Via genetic linkage analysis, we found that the abnormal phenotype of pds manifesting as genetic incompatibility or hybrid weakness was caused by genetic interaction between a recessive locus, pds1, which was derived from S142 and mapped to chromosome 8, and a locus pds2, which not yet mapped from 430. We fine-mapped pds1 to an approximately 55-kb interval delimited by the markers pds-4 and 8 M3.51. Six RGAP-annotated ORFs were included in this genomic region. qPCR analysis revealed that Loc_Os080595 might be the target of pds1 locus, and G1 gene might be involved in the genetic mechanism underlying the pds phenotype. CONCLUSIONS: In this study, histological and genetic analyses revealed that the pyramided pds loci resulted in genetic incompatibility or hybrid weakness in rice might be caused by a genetic interaction between pds loci derived from different rice varieties. Further isolation of pds1 and its interactor pds2, would provide new insight into the molecular regulation of grass inflorescence development and exsertion, and the evolution history of the extant rice.


Assuntos
Oryza/genética , Mapeamento Cromossômico , Flores/crescimento & desenvolvimento , Flores/ultraestrutura , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Genes de Plantas/fisiologia , Estudos de Associação Genética , Loci Gênicos , Microscopia Eletrônica de Varredura , Oryza/crescimento & desenvolvimento , Oryza/ultraestrutura , Reação em Cadeia da Polimerase em Tempo Real
14.
Medicine (Baltimore) ; 98(20): e15247, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096432

RESUMO

The aim of the current study was to investigate the expression of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in allergic rhinitis (AR) patients, and to further explore the association of lncRNA ANRIL expression with AR risk, severity, and inflammation.In this case-control study, 96 AR patients and 96 non-atopic obstructive snoring patients who underwent adenoid surgery were consecutively recruited. Disease severity of AR patients was assessed via individual nasal symptom score (INSS) and total nasal symptom score (TNSS). Nasal mucosa samples were collected from AR patients and controls, then lncRNA ANRIL and inflammatory cytokine levels were assessed via quantitative polymerase chain reaction.LncRNA ANRIL expression was increased in AR patients (3.605 [1.763-4.981]) compared with controls (1.183 [0.438-2.985]), and it well distinguished AR patients from controls with an area under curve of 0.746 (95% CI: 0.679-0.814). Correlation analyses revealed that lncRNA ANRIL expression was positively associated with itching score and congestion score, while it was not associated with nasal rhinorrhea score or sneezing score. Besides, lncRNA ANRIL was also positively correlated with TNSS, tumor necrosis factor α, interleukin (IL)-4, IL-6, IL-13, and IL-17, while negatively associated with IL-10 and interferon-γ. And no association of lncRNA ANRIL expression with IL-1ß, IL-5, or IL-8 expression was discovered.LncRNA ANRIL expression correlates with increased AR risk, severity, and inflammation, implying that lncRNA ANRIL might be involved in the pathogenesis of AR.


Assuntos
Loci Gênicos/genética , Inflamação/metabolismo , Mucosa Nasal/metabolismo , RNA Longo não Codificante/genética , Rinite Alérgica/genética , Adolescente , Adulto , Estudos de Casos e Controles , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Inflamação/patologia , Interleucina-1beta/metabolismo , Interleucina-5/metabolismo , Interleucina-8/metabolismo , Masculino , Mucosa Nasal/patologia , Fragmentos de Peptídeos/metabolismo , Rinite Alérgica/patologia , Rinite Alérgica/cirurgia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
15.
Nat Commun ; 10(1): 2128, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086182

RESUMO

Drug resistance diagnostics that rely on the detection of resistance-related mutations could expedite patient care and TB eradication. We perform minimum inhibitory concentration testing for 12 anti-TB drugs together with Illumina whole-genome sequencing on 1452 clinical Mycobacterium tuberculosis (MTB) isolates. We evaluate genome-wide associations between mutations in MTB genes or non-coding regions and resistance, followed by validation in an independent data set of 792 patient isolates. We confirm associations at 13 non-canonical loci, with two involving non-coding regions. Promoter mutations are measured to have smaller average effects on resistance than gene body mutations. We estimate the heritability of the resistance phenotype to 11 anti-TB drugs and identify a lower than expected contribution from known resistance genes. This study highlights the complexity of the genomic mechanisms associated with the MTB resistance phenotype, including the relatively large number of potentially causal loci, and emphasizes the contribution of the non-coding portion of the genome.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano/genética , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Análise Mutacional de DNA , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Regiões Promotoras Genéticas/genética , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Sequenciamento Completo do Genoma
16.
Nat Genet ; 51(6): 1011-1023, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31110352

RESUMO

It is not clear how spontaneous DNA double-strand breaks (DSBs) form and are processed in normal cells, and whether they predispose to cancer-associated translocations. We show that DSBs in normal mammary cells form upon release of paused RNA polymerase II (Pol II) at promoters, 5' splice sites and active enhancers, and are processed by end-joining in the absence of a canonical DNA-damage response. Logistic and causal-association models showed that Pol II pausing at long genes is the main predictor and determinant of DSBs. Damaged introns with paused Pol II-pS5, TOP2B and XRCC4 are enriched in translocation breakpoints, and map at topologically associating domain boundary-flanking regions showing high interaction frequencies with distal loci. Thus, in unperturbed growth conditions, release of paused Pol II at specific loci and chromatin territories favors DSB formation, leading to chromosomal translocations.


Assuntos
Quebras de DNA de Cadeia Dupla , Loci Gênicos , Neoplasias/genética , Neoplasias/metabolismo , RNA Polimerase II/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Reparo do DNA , Elementos Facilitadores Genéticos , Etoposídeo/farmacologia , Citometria de Fluxo , Imunofluorescência , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genômica/métodos , Íntrons , Neoplasias/patologia , Regiões Promotoras Genéticas , Sítios de Splice de RNA , Inibidores da Topoisomerase/farmacologia , Sítio de Iniciação de Transcrição
17.
J Dairy Sci ; 102(7): 5979-6000, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31128867

RESUMO

Some gram-negative bacteria, including Pseudomonas spp., can grow at refrigeration temperatures and cause flavor, odor, and texture defects in fluid milk. Historical and modern cases exist of gray and blue color defects in fluid milk due to Pseudomonas, and several recent reports have detailed fresh cheese spoilage associated with blue-pigment-forming Pseudomonas. Our goal was to investigate the genomes of pigmented Pseudomonas isolates responsible for historical and modern pigmented spoilage of dairy products in the United States to determine the genetic basis of pigment-forming phenotypes. We performed whole genome sequencing of 9 Pseudomonas isolates: 3 from recent incidents of gray-pigmented fluid milk (Pseudomonas fluorescens group), 1 from blue-pigmented cheese (P. fluorescens group), 2 from a historical blue milk spoilage incident (Pseudomonas putida group), and 3 with no evidence for blue or gray pigment formation (2 from P. fluorescens group and 1 from Pseudomonas chlororaphis group). All 6 isolates collected from products with a gray or blue pigment defect were confirmed to produce pigment using potato dextrose agar or pasteurized milk. A subset of 2 isolates was selected for inoculation into milk and onto the surface of a model cheese for subsequent color measurement. These isolates produced different colors on potato dextrose agar, but produced nearly identical color defects in milk and on model cheese. For the same subset of 2 isolates, the gray color defect in milk was produced only in containers with ample headspace and not in full containers, suggesting that oxygen is vital for pigment formation. This work also demonstrated that a Pseudomonas isolate from cheese can produce a pigment defect in milk, and vice versa. Comparative genomics identified an accessory locus encoding tryptophan biosynthesis genes that was present in all isolates that produced gray or blue pigment under laboratory conditions and was only previously reported in 2 P. fluorescens isolates responsible for blue mozzarella in Italy. Because this locus was found in genetically distant isolates belonging to different Pseudomonas species groups, it may have been acquired via horizontal gene transfer. These data suggest that several past and present gray- or blue-pigmented dairy spoilage events share a common genetic etiology that transcends species-level identification and merits further investigation to determine mechanistic details and modes of prevention.


Assuntos
Queijo/análise , Genoma Bacteriano/fisiologia , Leite/química , Pseudomonas fluorescens/genética , Pseudomonas putida/genética , Animais , Queijo/microbiologia , Cor , Loci Gênicos/fisiologia , Genômica , Itália , Leite/microbiologia , Fenótipo , Pigmentação , Pigmentos Biológicos/biossíntese , Pseudomonas fluorescens/metabolismo , Pseudomonas putida/metabolismo
18.
Nat Genet ; 51(6): 1024-1034, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31133748

RESUMO

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , RNA Longo não Codificante/genética , Inativação do Cromossomo X , Animais , Diferenciação Celular/genética , Expressão Ectópica do Gene , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Feminino , Inativação Gênica , Loci Gênicos , Masculino , Camundongos , Modelos Biológicos , Regiões Promotoras Genéticas , Inversão de Sequência , Transcrição Genética
19.
BMC Plant Biol ; 19(1): 183, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060503

RESUMO

BACKGROUND: Triticum timopheevii (2n = 4x = 28; AtAtGG), is an important source for new genetic variation for wheat improvement with genes for potential disease resistance and salt tolerance. By generating a range of interspecific hybrid lines, T. timopheevii can contribute to wheat's narrow gene-pool and be practically utilised in wheat breeding programmes. Previous studies that have generated such introgression lines between wheat and its wild relatives have been unable to use high-throughput methods to detect the presence of wild relative segments in such lines. RESULTS: A whole genome introgression approach, exploiting homoeologous recombination in the absence of the Ph1 locus, has resulted in the transfer of different chromosome segments from both the At and G genomes of T. timopheevii into wheat. These introgressions have been detected and characterised using single nucleotide polymorphism (SNP) markers present on a high-throughput Axiom® Genotyping Array. The analysis of these interspecific hybrid lines has resulted in the detection of 276 putative unique introgressions from T. timopheevii, thereby allowing the generation of a genetic map of T. timopheevii containing 1582 SNP markers, spread across 14 linkage groups representing each of the seven chromosomes of the At and G genomes of T. timopheevii. The genotyping of the hybrid lines was validated through fluorescence in situ hybridisation (FISH). Comparative analysis of the genetic map of T. timopheevii and the physical map of the hexaploid wheat genome showed that synteny between the two species is highly conserved at the macro-level and confirmed the presence of inter- and intra-genomic translocations within the At and G genomes of T. timopheevii that have been previously only detected through cytological techniques. CONCLUSIONS: In this work, we report a set of SNP markers present on a high-throughput genotyping array, able to detect the presence of T. timopheevii in a hexaploid wheat background making it a potentially valuable tool for marker assisted selection (MAS) in wheat pre-breeding programs. These valuable resources of high-density molecular markers and wheat-T. timopheevii hybrid lines will greatly enhance the work being undertaken for wheat improvement through wild relative introgressions.


Assuntos
Genoma de Planta , Hibridização Genética , Poliploidia , Triticum/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Ecótipo , Ligação Genética , Loci Gênicos , Marcadores Genéticos , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Recombinação Genética/genética , Sementes/genética , Especificidade da Espécie
20.
Nat Commun ; 10(1): 2054, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053729

RESUMO

Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10-42, ß = -0.090) and confers risk of hip fracture (P = 1.0 × 10-8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.


Assuntos
Densidade Óssea/genética , Fraturas do Quadril/genética , MicroRNAs/genética , Osteoartrite/genética , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estatura/genética , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Estudos de Casos e Controles , Colágeno Tipo XI/genética , Feminino , Seguimentos , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Fator 5 de Diferenciação de Crescimento/genética , Fraturas do Quadril/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/epidemiologia , Fatores de Risco
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