Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization.

Several general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically probe heterogeneity in genome organization. High-throughput optical mapping of several hundred intra-chromosomal interactions in individual human fibroblasts demonstrates low association frequencies, which are determined by genomic distance, higher-order chromatin architecture, and chromatin environment. The structure of TADs is variable between individual cells, and inter-TAD associations are common. Furthermore, single-cell analysis reveals independent behavior of individual alleles in single nuclei. Our observations reveal extensive variability and heterogeneity in genome organization at the level of individual alleles and demonstrate the coexistence of a broad spectrum of genome configurations in a cell population.

Diagnóstico molecular de Porphyromonas gingivalis: optimización del método / Molecular diagnosis of Porphyromonas gingivalis: optimization of the method

El objetivo del presente trabajo fue estandarizar y optimizar la técnica de PCR convencional para detección de Porphyromonas gingivalis ATCC 33277. Materiales y métodos: la cepa de P. gingivalis ATCC332227 se sembró en agar Bruella enriquecido con sangre de cordero, suplementado con hemina y vitamina K. El ADN se extrajo empleando el protocolo que usa bromuro de cetil trimetilamonio (CTAB). Se evaluó la cantidad y calidad del material genético obtenido con el fotómetro UV Ampli-Quat, AQ-07 Nucleic Acid. Se realizó la PCR convencional con diferentes concentraciones de MgCl2 1 mM, 1,5 mM y 2.0 mM y a dos temperaturas de alineamiento: 60ºC y 55ºC. Los productos PCR se separaron por electroforesis en un gel de agarosa 1 por ciento. Las bandas se visualizaron en un fotodocumentador. La sensibilidad se calculó teniendo en cuenta el número de bacterias en diferentes diluciones. Resultados: se obtuvo una concentración 1,55x10(6) ng/ul de ADN genómico a partir de una suspensión bacteriana de 10a células bacterianas/ml, con índice de pureza 1,648 (relación de OD260/OD280). Los mejores resultados se obtuvieron con una concentración de 2 mM de MgCl2 y una temperatura de alineación de 55ºC. En cuanto a la sensibilidad, se obtuvo un límite de detección de 5 x 10/5 uL células bacterianas en suspensión. Conclusión: en la prueba de PCR convencional para Prophyromonas gingivalis ATCC 33277, las condiciones óptimas de estandarización son la concentración de 2 mM de MgCl y 55ºC y es necesaria una carga bacteriana mínima de 5 x 10 células/5 ul como límite de detección.

Transposable elements in the genomes: parasites, junks or drivers of evolution?

In many organisms with large and complex genomes, transposable elements (TEs) constitute up to 50% of the genomic DNA. TEs have been widely studied and they showed high similarities across kingdoms. Several reasons have been adduced for the diverse TEs among plants and animal species. Activities of TEs could give rise to altered gene or genome at very high frequencies in both germinal and somatic tissues. TE-induced genetic variability can range widely; from changes in the arrangement of the whole genome to changes in single nucleotides. This may produce major effects on the phenotypic traits or small silent changes detectable only at the DNA sequence level. TE-induced mutation in the regulatory sequences may be of evolutionary significance and insertions in promoter sequences can alter tissue-specific patterns of gene expression. In addition, transposons can be involved in amplification and dispersal of genes by taking up portions of other sequences within the TEs themselves, moving them to new locations, thereby increasing their copy number. Therefore, mobilization of TEs might benefit the host through enhancement of genetic diversity. However, TE movement have been linked with undesirable traits in plants, hybrid dysgenesis in Drosophila and genome instability and diseases in mammals. This review summarises the diversity of TEs across plant and animal kingdoms and their impact and possible role in genomic evolution. It also describes some adverse effects of TEs as agents of genomic instability and diseases such as cancers, and the genetic regulations of their activities.

Maintaining cell identity through global control of genomic organization.

Cell differentiation entails early lineage choices leading to the activation, and the subsequent maintenance, of the gene expression program characteristic of each cell type. Alternative lineage choices involve the activation of different regulatory and coding regions of the genome, a process instructed by lineage-determining transcription factors, and at least in part mediated by the deposition of chromatin marks that modify functionality and accessibility of the underlying genome. According to classic epigenetics, subsequent maintenance of chromatin marks across mitoses and in spite of environmental perturbations occurs largely through autonomous and unsupervised mechanisms. However, paradigmatic genetic and biochemical studies in immune system and hematopoietic cells strongly point to the concept that both induction and maintenance of the differentiated state require constant supervision by lineage-determining transcription factors, which may act to globally organize the genome in both the one- and the three-dimensional space.

Using genomics to understand intestinal biology

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The use of microarrays to evaluate the transcriptome has transformed our view ofbiology. In addition to the focused, hypothesis-testing studies that we have traditionallyconducted in cell biology, we are now able to see global changes within theentire system of the cell in response to a treatment. By examining a biological questionunder multiple complementary perturbations model systems (e.g. yeast, C. Elegans)have revealed new complexity that would have been impossible to see on agene-by-gene approach. Unfortunately, beyond the use of transcript profiles todefine the molecular signature of diseases (e.g. cancer), transcriptomics has not beenextensively used to study intestinal biology. This review will provide a roadmap foreffective use of gene expression profiling for biological research and will review someof the microarray work that has been done to better understand the nature of intestinal development and enterocyte differentiation (AU)

Odontología genómica: la medicina oral del siglo XXI / Genomic dentistry: the oral medicine of 21st century

Los avances tecnológicos y la culminación del Proyecto Genoma Humano y con él la secuencia de 3.200 millones de los nucleótidos o de las letras (A-T/G-C) que la componen, y los aproximadamente 1.400 genes que pueden ser las causas de enfermedades consideradas hasta este momento como genéticas, han cambiado la cara de las investigaciones biológicas y han colocado a la genómica en la vanguardia de la ciencia biomédica. En la periodontología, así como en la medicina, estamos muy interesados en la genética y en los diferentes acomodos o polimorfismos de los nucleótidos (SNIPs), tanto en los humanos como en los patógenos, así como la interacción genética entre ellos

[Active oxygen forms and genome damage by environmental factors]. / Rol' svobodnoradikal'nogo okisleniia v povrezhdenii genoma faktorami okruzhaiushchei sredy.

The role played by active oxygen forms in damaging the human genome by environmental factors as well as the application of antioxidants to keep the oncology statistics among the hazardous-area residents low are under discussion. According to the independent results, there are essential differences between mechanisms of inflicting a genetic lesion to healthy subjects and to individuals of the risk categories due to that the latter have contacts with high concentrations of chemical compounds and with clinical patients with developed free-radical pathologies.