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1.
Zhonghua Shao Shang Za Zhi ; 36(1): 14-23, 2020 Jan 20.
Artículo en Chino | MEDLINE | ID: mdl-32023713

RESUMEN

Objective: To isolate a bacteriophage against pan-drug resistant Klebsiella pneumoniae in a burn patient, and to study its biological characteristics, genomic information, and effects on bacterial biofilm. Methods: (1) In 2018, pan-drug resistant Klebsiella pneumoniae UA168 (hereinafter referred to as the host bacteria) solution isolated from the blood of a burn patient in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (hereinafter referred to as Ruijin Hospital) was used to isolate and purify the bacteriophage against pan-drug resistant Klebsiella pneumoniae from the sewage of Ruijin Hospital with sewage co-culture method, drip plate method, and double-agar plate method. The bacteriophage was named as phage KP168 and the plaque morphology was observed. (2) The phage KP168 solution was taken for cesium chloride density gradient centrifugation and dialysis, and then the morphology of phage KP168 was observed through transmission electron microscope after phosphotungstic acid negative staining. (3) The phage KP168 solution was taken to determine the lytic ability of the phage KP168 against 20 strains of pan-drug resistant Klebsiella pneumoniae isolated from the burned patients' blood in Ruijin Hospital by the drip plate method, and then the lysis rate was calculated. (4) The phage KP168 solution at a initial titer of 9.3×10(11) plaque-forming unit (PFU)/mL (400 µL per tube) and the host bacteria solution at a concentration of 1×10(9) colony-forming unit (CFU)/mL (4 mL per tube) were conventionally shaking cultured together for 4 hours at multiplicity of infection (MOI) of 10.000, 1.000, 0.100, 0.010, or 0.001, respectively (1 tube per MOI). The titer of phage KP168 was measured by the double-agar plate method (the measurement method was the same below) to select the optimal MOI. The experiment was repeated three times. (5) The host bacteria solution at a concentration of 1×10(9) CFU/mL (4 mL per tube) and the phage KP168 solution at an adjusted titer of 5×10(7) PFU/mL (400 µL per tube) were mixed at the MOI of 0.005. The plaques were counted 0 (immediately), 1, 2, 3, 4, 5, 15, and 30 minutes (1 tube at each time point) after mixing by the double-agar plate method (the counting method was the same below), and the percentage of adsorbed phages was calculated to screen for the optimal adsorption time. The experiment was repeated three times. (6) The host bacteria solution at a concentration of 1×10(9) CFU/mL (300 µL per tube) and the phage KP168 solution at a titer of 5×10(8) PFU/mL (60 µL per tube) were mixed at MOI of 0.005 and conventionally shaking cultured after standing for the optimal adsorption time. The phage KP168 titer was measured 0 (immediately), 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 minutes after culture, and a one-step growth curve was drawn. The experiment was repeated three times. (7) The phage KP168 solution at a titer of 2.5×10(10) PFU/mL was left to stand for 1 hour at 37, 40, 50, 60, or 70 ℃ (3 tubes at each time point, 1 mL per tube) for counting the plaques, and then the thermal stability curve was drawn. SM buffer at a pH values of 5.0, 6.0, 7.0, 7.4, 8.0, 9.0, or 10.0 were added to the phage KP168 solution at a titer of 3.0×10(10) PFU/mL, respectively. The mixed solution was left to stand for 1 hour at 37 ℃ (3 tubes of each pH, each tube containing 100 µL phage KP168 solution and 900 µL SM buffer), and then the plaques were counted, and an acid-base stability curve was drawn. (8) The phage KP168 solution was taken for DNA extraction and sequencing after dialysis as in experiment (2). The whole genome was annotated with Prokka to obtain the coding sequence of phage KP168. Nucleotide's BLAST function was used to proceed nucleic acid sequence alignment for finding a known phage with the highest similarity to the phage KP168 nucleic acid sequence, and Blastx function was used to translate the coding sequence into protein for its function prediction. The comparison with Antibiotic Resistance Genes Database and Virulence Factors Database was proceeded. (9) In a 96-well plate, at a MOI of 1.000, 0.100, 0.010 or 0.001 (3 wells per MOI), 20 µL phage KP168 solution at a initial titer of 5.8×10(10) PFU/mL was added to 200 µL host bacteria solution at a concentration of 1.5×10(8) CFU/mL (the same concentration below) for co-cultivation for 48 hours. After 200 µL host bacteria solution was left to stand for 48 hours, 20 µL phage KP168 solution at a titer of 1×10(6,) 1×10(7,) 1×10(8,) 1×10(9,) or 1×10(10) PFU/mL (3 wells per titer) was added respectively for action for 4 hours. In both experiments, 200 µL host bacteria solution added with 20 µL SM buffer (3 wells) acted as a negative control, and 220 µL LB culture medium (3 wells) acted as a blank control. Absorbance values were measured by a microplate reader, and inhibition/destruction rates of biofilm were calculated. The experiments were both repeated three times. Results: (1) The plaques of phage KP168 successfully isolated and purified were transparent and round, and its diameter was approximately 1.5 mm. (2) The phage KP168 has a regular polyhedron structure with a diameter of about 50 nm and without a tail. (3) The phage KP168 could lyse 13 of 20 strains of Klebsiella pneumoniae from burned patients, with a lysis rate of 65.0%. (4) When MOI was 1.000, the titer was the highest after co-culturing the phage KP168 with the host bacteria for 4 hours, which was the optimal MOI. (5) After the mixing of the phage KP168 with the host bacteria for 4 minutes, the percentage of the adsorbed phage reached the highest, which was the optimal adsorption time. (6) The one-step growth curve showed that during the lysis of the host bacteria by phage KP168, the incubation period was about 10 minutes, and the lysis period was about 40 minutes. (7) With the condition of 40 ℃ or pH 7.4, the number of plaques and the activity of phage KP168 reached the highest. (8) The genome of phage KP168 was a linear double-stranded DNA with a length of 40 114 bp. There were 48 possible coding sequences. It had the highest similarity to Klebsiella phage_vB_Kp1. The most similar known proteins corresponding to the translated proteins of coding sequences contained 23 hypothetical proteins and 25 proteins with known functions. No resistance genes or virulence factor genes were found. The GeneBank accession number was KT367885. (9) After 48 hours of co-cultivation of the phage KP168 and the host bacteria at each MOI, the inhibition rates of biofilm were similar, with an average of about 45%. After the phage KP168 with a titer of 1×10(9) PFU/mL acted on the biofilm formed by the host bacteria for 4 h, the destruction rate of biofilm was the highest, reaching an average of 42%. Conclusions: In this study, a bacteriophage against pan-drug resistant Klebsiella pneumoniae from a burn patient, phage KP168, is isolated from sewage, which belongs to the tailless phage. It has a wide host spectrum, short adsorption time, and short incubation period, with certain thermal and acid-base stability. Its genomic information is clear, and it does not contain resistance genes or virulence factor genes. It also has an inhibitory effect on the formation of bacterial biofilm and a destructive effect on the formed bacterial biofilm.


Asunto(s)
Bacteriófagos , Quemaduras , Biopelículas , China , Genómica , Humanos , Klebsiella pneumoniae
4.
Adv Neurobiol ; 24: 83-96, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32006357

RESUMEN

Autism spectrum disorder (ASD) is a heterogeneous condition affecting >1% of all children, characterized by impaired social interactions, repetitive behavior and a widely variable spectrum of comorbidities. These comorbidities may include developmental delay, gastrointestinal problems, cardiac disorders, immune and autoimmune dysregulation, neurological manifestations (e.g., epilepsy, intellectual disability), and other clinical features. This wide phenotypic heterogeneity is difficult to predict and manifests across a wide range of ages and with a high degree of difference in severity, making disease management and prediction of a successful intervention very difficult. Recently, advances in genomics and other molecular technologies have enabled the study of ASD on a molecular level, illuminating genes and pathways whose perturbations help explain the clinical variability among patients, and whose impairments provide possible opportunities for better treatment options. In fact, there are now >1000 genes that have been linked to ASD through genetic studies of more than 10,000 patients and their families. This chapter discusses these discoveries and in the context of recent developments in genomics and bioinformatics, while also examining the trajectory of gene discovery efforts over the past few decades, as both better ascertainment and global attention have been given to this highly vulnerable patient population.


Asunto(s)
Trastorno del Espectro Autista/genética , Genoma Humano/genética , Genómica , Trastorno del Espectro Autista/complicaciones , Discapacidades del Desarrollo/complicaciones , Discapacidades del Desarrollo/genética , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/genética
5.
Anticancer Res ; 40(1): 535-543, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892609

RESUMEN

BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.


Asunto(s)
Suplementos Dietéticos , Genómica , Metabolómica , Vitamina D/farmacología , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Hormona Paratiroidea/sangre , Análisis de Componente Principal , Mapas de Interacción de Proteínas/efectos de los fármacos , Vitamina D/análogos & derivados , Vitamina D/sangre
6.
Ecol Lett ; 23(3): 495-505, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31919988

RESUMEN

Many generalist species consist of specialised individuals that use different resources. This within-population niche variation can stabilise population and community dynamics. Consequently, ecologists wish to identify environmental settings that promote such variation. Theory predicts that environments with greater resource diversity favour ecological diversity among consumers (via disruptive selection or plasticity). Alternatively, niche variation might be a side-effect of neutral genomic diversity in larger populations. We tested these alternatives in a metapopulation of threespine stickleback. Stickleback consume benthic and limnetic invertebrates, focusing on the former in small lakes, the latter in large lakes. Intermediate-sized lakes support generalist stickleback populations using an even mixture of the two prey types, and exhibit greater among-individual variation in diet and morphology. In contrast, genomic diversity increases with lake size. Thus, phenotypic diversity and neutral genetic polymorphism are decoupled: trophic diversity being greatest in intermediate-sized lakes with high resource diversity, whereas neutral genetic diversity is greatest in the largest lakes.


Asunto(s)
Smegmamorpha , Animales , Dieta , Variación Genética , Genómica , Invertebrados , Lagos
7.
Yi Chuan ; 42(1): 18-31, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31956094

RESUMEN

CRISPR/Cas9 system has significant advantages in gene editing strategy, offering cost-effective and efficient means to modify and edit the genomes of animals, plants, and microorganisms. Three-dimensional (3D) genome is an emerging and interdisciplinary field catapulted by combined technological breakthroughs of chromosome conformation capture with next-generation sequencing and live imaging with super-resolution microscopy. An important aspect of 3D genomics is to model structural variations and label specific genomic fragments to investigate the effects of manipulation of genomic elements on gene expression regulation, cell development and differentiation, and spatial location of chromosomal regions. Therefore, CRISPR/Cas9 system and its derivative technologies of DNA-fragment editing are excellent toolboxes for investigating dynamics and functions of the higher-order chromatin organization and three-dimensional genome structure. In this review, we describe the opportunities and challenges of CRISPR as well as its derivative technologies in 3D genome research, thereby providing some critical references and future research directions in the field.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Genómica , Genoma
8.
Yi Chuan ; 42(1): 32-44, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31956095

RESUMEN

The eukaryotic chromatin is folded into highly complex three-dimensional (3D) structures, which plays an important role in the precise regulation of gene expression and normal physiological function. During differentiation and terminal maturation, cells usually undergo dramatic morphology and gene expression changes, accompanied by significant changes in the 3D structure of the genome. In this review, we provide a comprehensive view of the spatial hierarchical organization of the genome, including chromosome territories, A/B compartment, topologically associating domains (TADs) and looping, focusing on recent progresses in the dynamic 3D genomic structural changes and functional regulation during cell differentiation and terminal maturation. In the end, we summarize the unsolved issues as well as prospects of the 3D genome research in cell differentiation and maturation.


Asunto(s)
Diferenciación Celular , Ensamble y Desensamble de Cromatina , Cromatina/química , Genoma , Genómica
9.
Yi Chuan ; 42(1): 87-99, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31956099

RESUMEN

The spatial interaction of chromosomes is regarded as an important issue affecting the regulation of gene expression, and the high-throughput chromosome conformation capture (Hi-C) technology has become the primary tool to explore the temporal and spatial interactions of chromosomes in three-dimensional genomics. With the continuous accumulation of Hi-C samples and the increasing complexity of pipelines, the bioinformatic analysis of Hi-C data has been considered an opportunity and a challenge for understanding the spatial regulation mechanism of gene expression. In this paper, the current status and development outline of bioinformatic methods for Hi-C data are introduced, including data normalization, multi-level structure analysis, data visualization and 3D modeling, especially of multi-level structure at A/B compartments, topological associated domains (TADs) and chromain looping levels. Based on this, we provide the outlook of future hotspots and trends in this area. Hopefully our insight will be beneficial for the exploration of gene expression regulation from the traditional linear model to the 3D mode.


Asunto(s)
Cromosomas/química , Biología Computacional , Genómica , Cromatina/química
10.
Bioresour Technol ; 297: 122389, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31757614

RESUMEN

In this study, whole genome sequencing and comparative genomic analyses were performed for Mucilaginibacter polytrichastri RG4-7 and its carboxymethyl cellulose degradation potential was assessed. The results showed that the genome of strain RG4-7 was 5.84 Mb and contained 5019 predicted genes, in which a high proportion of strain-specific genes were related to carbohydrate metabolism. The carboxymethyl cellulose (CMC) degradation and cellulase activity tests revealed the strong cellulose degradation ability, CMCase and ß-glucosidase activity in strain RG4-7. Real-time RT-PCR testing of most cellulose degradation related glycoside hydrolase (GH) families showed that GH9 (OKS85969), GH1 (OKS85832), GH3 (OKS89331 and OKS85615) were significantly up-regulated when strain RG4-7 was inoculated with CMC-Na, which suggested that GH9, GH1 and GH3 might determine its cellulose degradation ability. Certainly, further research need to be done to elucidate cellulose degradation mechanisms in strain RG4-7 in order to develop its industrial application value in lignocellulosic biomass degradation and waste management.


Asunto(s)
Celulasa , Celulosa , Bacteroidetes , Metabolismo de los Hidratos de Carbono , Genómica , Secuenciación Completa del Genoma
12.
Plant Dis ; 104(1): 13-15, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31660797

RESUMEN

Xanthomonas translucens pv. translucens causes bacterial leaf streak and bacterial blight diseases of barley. This pathogen limits barley production globally but remains understudied, with limited genomic resources. To better understand the biology of this X. translucens subgroup, we sequenced the complete genome of the X. translucens pv. translucens strain UPB886.


Asunto(s)
Genoma Bacteriano , Xanthomonas , Genoma Bacteriano/genética , Genómica , Hordeum/microbiología , Enfermedades de las Plantas/microbiología , Xanthomonas/genética
13.
Trends Ecol Evol ; 35(1): 34-42, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31703819

RESUMEN

Hybridization has broad evolutionary consequences, from fueling or counteracting speciation to facilitating adaptation to novel environments. Hybridization and subsequent introgression appear widespread along the tree of life. However, our understanding of how distinct evolutionary forces shape admixed genomes and the fate of introgressed genetic variants remains scarce. Most admixture research in animals has focused on diploid organisms. We propose that haplodiploid organisms can help resolve open questions about the genomic consequences of hybridization in natural populations. The ploidy difference between haploid males and diploid females, the availability of genome-wide male haplotypes, and ongoing cases of admixture make haplodiploid organisms promising models to improve our knowledge with regards to the evolution of hybrid genomes.


Asunto(s)
Diploidia , Hibridación Genética , Animales , Femenino , Genómica , Haploidia , Masculino
14.
Hum Genet ; 139(1): 85-94, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31520123

RESUMEN

In recent years, genome-wide association study (GWAS) sample sizes have become larger, the statistical power has improved and thousands of trait-associated variants have been uncovered, offering new insights into the genetic etiology of complex human traits and disorders. However, a large fraction of the polygenic architecture underlying most complex phenotypes still remains undetected. We here review the conditional false discovery rate (condFDR) method, a model-free strategy for analysis of GWAS summary data, which has improved yield of existing GWAS and provided novel findings of genetic overlap between a wide range of complex human phenotypes, including psychiatric, cardiovascular, and neurological disorders, as well as psychological and cognitive traits. The condFDR method was inspired by Empirical Bayes approaches and leverages auxiliary genetic information to improve statistical power for discovery of single-nucleotide polymorphisms (SNPs). The cross-trait condFDR strategy analyses separate GWAS data, and leverages overlapping SNP associations, i.e., cross-trait enrichment, to increase discovery of trait-associated SNPs. The extension of the condFDR approach to conjunctional FDR (conjFDR) identifies shared genomic loci between two phenotypes. The conjFDR approach allows for detection of shared genomic associations irrespective of the genetic correlation between the phenotypes, often revealing a mixture of antagonistic and agonistic directional effects among the shared loci. This review provides a methodological comparison between condFDR and other relevant cross-trait analytical tools and demonstrates how condFDR analysis may provide novel insights into the genetic relationship between complex phenotypes.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genómica/métodos , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Humanos , Fenotipo
15.
Mol Genet Genomics ; 295(1): 177-193, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31620884

RESUMEN

Genetic variation is expressed by the presence of polymorphisms in compared genomes of individuals that can be transferred to next generations. The aim of this work was to reveal genome dynamics by predicting polymorphisms among the genomes of three individuals of the highly inbred B10 cucumber (Cucumis sativus L.) line. In this study, bioinformatic comparative genomics was used to uncover cucumber genome dynamics (also called real-time evolution). We obtained a new genome draft assembly from long single molecule real-time (SMRT) sequencing reads and used short paired-end read data from three individuals to analyse the polymorphisms. Using this approach, we uncovered differentiation aspects in the genomes of the inbred B10 line. The newly assembled genome sequence (B10v3) has the highest contiguity and quality characteristics among the currently available cucumber genome draft sequences. Standard and newly designed approaches were used to predict single nucleotide and structural variants that were unique among the three individual genomes. Some of the variant predictions spanned protein-coding genes and their promoters, and some were in the neighbourhood of annotated interspersed repetitive elements, indicating that the highly inbred homozygous plants remained genetically dynamic. This is the first bioinformatic comparative genomics study of a single highly inbred plant line. For this project, we developed a polymorphism prediction method with optimized precision parameters, which allowed the effective detection of small nucleotide variants (SNVs). This methodology could significantly improve bioinformatic pipelines for comparative genomics and thus has great practical potential in genomic metadata handling.


Asunto(s)
Cucumis sativus/genética , Genoma de Planta/genética , Mapeo Cromosómico/métodos , Biología Computacional/métodos , Genómica/métodos , Anotación de Secuencia Molecular/métodos , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética
17.
Hum Genet ; 139(1): 115-120, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31006046

RESUMEN

Much of modern genomics and the other 'omics' that tag along, assert that the causal bases of biomedical outcomes are genomically enumerable lists whose effects are predictable with 'precision', extensible from samples to all, and enabled by ever-greater hypothesis-free data accumulation. The assertion rests on fundamental, if often implicit assumptions, that (1) the phenomena are based on underlying law-like biological causation, and, therefore, are (2) replicable and (3) even if not deterministic, have specifiable, stable, essentially parametric, probabilities, all of which (4) essentially equates induction with deduction, enabling asymptotically accurate prediction based on past observation. These glowing promises are the four horsemen of a genocentric 'Omicsalypse'. But what if the assumptions are wrong or appropriate only to an extent that is unknowable, even in principle? Might there be better ways to understand complex traits?


Asunto(s)
Ontología de Genes , Genómica/métodos , Humanos , Probabilidad , Reproducibilidad de los Resultados
18.
Plant Dis ; 104(1): 60-70, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31647693

RESUMEN

Rapid detection is key to managing emerging diseases because it allows their spread around the world to be monitored and limited. The first major wheat blast epidemics were reported in 1985 in the Brazilian state of Paraná. Following this outbreak, the disease quickly spread to neighboring regions and countries and, in 2016, the first report of wheat blast disease outside South America was released. This Asian outbreak was due to the trade of infected South American seed, demonstrating the importance of detection tests in order to avoid importing contaminated biological material into regions free from the pathogen. Genomic analysis has revealed that one particular lineage within the fungal species Pyricularia oryzae is associated with this disease: the Triticum lineage. A comparison of 81 Pyricularia genomes highlighted polymorphisms specific to the Triticum lineage, and this study developed a real-time PCR test targeting one of these polymorphisms. The test's performance was then evaluated in order to measure its analytical specificity, analytical sensitivity, and robustness. The C17 quantitative PCR test detected isolates belonging to the Triticum lineage with high sensitivity, down to 13 plasmid copies or 1 pg of genomic DNA per reaction tube. The blast-based approach developed here to study P. oryzae can be transposed to other emerging diseases.


Asunto(s)
Agricultura , Genoma Fúngico , Magnaporthe , Reacción en Cadena en Tiempo Real de la Polimerasa , Triticum , Agricultura/métodos , Genes Fúngicos/genética , Genómica , Magnaporthe/genética , Enfermedades de las Plantas/microbiología , América del Sur , Triticum/microbiología
19.
Gene ; 726: 144174, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-31647999

RESUMEN

At least 1/3 of all acquired solid cancers produce unusual cyst-like structures (CLSs, PGCCs) with simultaneous loss of p53 function. However, p53 deficiency or accumulated mutations are not the causes of aCLS cancers. The cause is the reversal, to unicellularity, of a metabolic stressed cell by activating silenced transition switches and ancestral gene networks inherited from early Metazoans. After reprogramming and transformation the cell-of-origin of cancer bypasses mitosis and forms the polyploid pCLS, the homemade pathogen of aCLS cancers. pCLS's daughter cells (microcells) generate the pretumorigenic cancer stem cell pool (pCSCs) that start in turn the unicellular cancer cell lineage containing reproductive and somatic sublines. While the reproductive subline gives rise to new autonomous aCLSs by asymmetric division and cyclic differentiation, the somatic subline grows aCLS free. In the course of cancer evolution, some of the somatic mutants convert to stem cell precursors (SCPs). Somatic SCPs transfer part of somatic mutations and epimutations to the genome of newly formed reproductive clones. In this way, subsequent generations of tumorigenic and metastatic CSCs are being produced. aCLS cancer development is neither chaotic nor deregulated it follows unicellular development patterns. The unicellular program is controlled by mechanisms from early eukaryotic evolution.


Asunto(s)
Carcinogénesis/genética , Epigénesis Genética/genética , Genoma/genética , Neoplasias/genética , Animales , Diferenciación Celular/genética , Linaje de la Célula/genética , Redes Reguladoras de Genes/genética , Genómica/métodos , Humanos , Estilo de Vida , Mutación/genética , Células Madre Neoplásicas/patología , Poliploidía
20.
Hum Genet ; 139(1): 95-102, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31317254

RESUMEN

A central goal in human genetics is the identification of variants and genes that influence the risk of polygenic diseases. In the past decade, genome-wide association studies (GWAS) have identified tens of thousands of genetic loci associated with various diseases. Since the majority of such loci lie within non-coding regions and have many candidate variants in linkage disequilibrium, it has been challenging to accurately identify specific causal variants and genes. To aid in their discovery a variety of statistical and experimental approaches have been developed. These approaches often borrow information from functional genomics assays such as ATAC-seq, ChIP-seq and RNA-seq to annotate functional variants and identify regulatory relationships between variants and genes. While such approaches are powerful, given the diversity of cell types and environments, it is paramount to select disease-relevant contexts for follow-up analyses. In this review, we discuss the latest developments, challenges, and best practices for determining the causal mechanisms of polygenic disease risk variants with functional genomics data from specialized cell types.


Asunto(s)
Linaje de la Célula/genética , Genes/genética , Genoma Humano , Estudio de Asociación del Genoma Completo , Genómica/métodos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Predisposición Genética a la Enfermedad , Humanos
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