RESUMEN

Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher's exact and/or chi-square test. Survival curves were estimated with Kaplan-Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.

Asunto(s)

Carcinogénesis/genética , Inestabilidad Cromosómica/genética , Neoplasias Colorrectales/genética , Inestabilidad de Microsatélites , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Chile/epidemiología , Neoplasias Colorrectales/clasificación , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Islas de CpG/genética , Metilación de ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética

RESUMEN

Los estudios citogenéticos se emplean con frecuencia en el diagnóstico de patologías que tienen como efecto la desestabilización de los cromosomas. Aun cuando los desórdenes identificados como síndromes de inestabilidad cromosómica son de causa genética, se desconoce que algunas infecciones por virus pueden provocar una desestabilización de los cromosomas. Un hallazgo frecuente en la clínica de estos pacientes es la microcefalia. El objetivo del presente trabajo fue analizar la asociación de la microcefalia con la inestabilidad cromosómica provocada tanto por enfermedades monogénicas como por infecciones virales. La base de datos Pubmed fue consultada para identificar cuáles síndromes con inestabilidad cromosómica y afecciones virales en estudios prenatales presentaban microcefalia como signo clínico. El sitio OMIM fue empleado para el análisis particularizado de las diversas patologías de origen genético. Ante el aumento reportado de la frecuencia de este signo clínico asociado a discapacidad intelectual en hijos de madres con infección por virus Zika confirmada durante el embarazo, resulta importante analizar el aumento del efecto desestabilizador en el genoma en pacientes infectados…(AU)

Asunto(s)

Humanos , Masculino , Femenino , Inestabilidad Cromosómica/genética , Virus Zika/genética , Microcefalia/genética , Análisis Citogenético

RESUMEN

BACKGROUND: The co-chaperone Hop [heat shock protein (HSP) organizing protein] has been shown to act as an adaptor for protein folding and maturation, in concert with Hsp70 and Hsp90. The hop gene is of eukaryotic origin. Likewise, the chloroplast elongation factor G (cEF-G) catalyzes the translocation step in chloroplast protein synthesis. The chl-fus gene, which encodes the cEF-G protein, is of plastid origin. Both proteins, Hop and cEF-G, derived from domain duplications. It was demonstrated that the nuclear chl-fus gene locates in opposite orientation to a hop gene in Glycine max. We explored 53 available plant genomes from Chlorophyta to higher plants, to determine whether the chl-fus gene was transferred directly downstream of the primordial hop in the proto-eukaryote host cell. Since both genes came from exon/module duplication events, we wanted to explore the involvement of introns in the early origin and the ensuing evolutionary changes in gene structure. RESULTS: We reconstructed the evolutionary history of the two convergent plant genes, on the basis of their gene structure, microsynteny and microcolinearity, from 53 plant nuclear genomes. Despite a high degree (72%) of microcolinearity among vascular plants, our results demonstrate that their adjacency was a product of chromosomal rearrangements. Based on predicted exon--intron structures, we inferred the molecular events giving rise to the current form of genes. Therefore, we propose a simple model of exon/module shuffling by intronic recombinations in which phase-0 introns were essential for domain duplication, and a phase-1 intron for transit peptide recruiting. Finally, we demonstrate a natural susceptibility of the intergenic region to recombine or delete, seriously threatening the integrity of the chl-fus gene for the future. CONCLUSIONS: Our results are consistent with the interpretation that the chl-fus gene was transferred from the chloroplast to a chromosome different from that of hop, in the primitive photosynthetic eukaryote, and much later before the appearance of angiosperms, it was recombined downstream of hop. Exon/module shuffling mediated by symmetric intron phases (i.e., phase-0 introns) was essential for gene evolution. The intergenic region is prone to recombine, risking the integrity of both genes.

Asunto(s)

Proteínas de Cloroplastos/genética , Cloroplastos/genética , Inestabilidad Cromosómica/genética , Recombinación Genética , Secuencia de Aminoácidos , Evolución Biológica , Genoma de Planta , Proteínas de Choque Térmico/genética , Intrones/genética , Plantas/genética , Pliegue de Proteína

RESUMEN

El cáncer colorrectal (CCR) es una de las principales causas de morbilidad y mortalidad a nivel mundial. Clásicamente se considera a los adenomas como las lesiones precursoras del CCR y se estipula un tiempo de 10 a 15 años para completar la secuencia adenoma-carcinoma. El CCR evoluciona a través de la acumulación progresiva de alteraciones genéticas y epigenéticas, las que conducen a la transformación de la mucosa colónica normal en cáncer invasivo. La identificación de diferentes vías moleculares de carcinogénesis colorrectal ha demostrado la naturaleza heterogénea del cáncer colónico. De reciente descripción, las lesiones aserradas muestran cambios moleculares y patológicos distintos a los adenomas tradicionales, estimándose que presentan un tiempo más acelerado de evolución hacia la malignidad. El objetivo de esta revisión es actualizar conocimientos sobre la génesis tumoral y sus bases biomoleculares a fin de posibilitar su aplicación a etapas clínicas concretas como la prevención y el tratamiento

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Colorectal cancer (CRC) is one of the main causes of morbidity and mortality worldwide. Adenomas are classically regarded as precursor lesions of CRC and between 10 and 15 years is thought to elapse to complete the adenoma-carcinoma sequence. CRC evolves through the progressive accumulation of genetic and epigenetic alterations that lead to invasive cancer through the transformation of normal colonic mucosa. The identification of different molecular pathways of colorectal carcinogenesis has demonstrated the heterogeneous nature of colon cancer. Recent description of serrated lesions shows molecular and pathological changes other than traditional adenomas with an estimated faster time of progression to malignancy. The aim of this review is to update the knowledge about tumorigenesis and its biomolecular basis for clinical application in early stages providing firm ground for prevention and treatment

Asunto(s)

Humanos , Adulto , Colonoscopía , Epigénesis Genética/genética , Genes Relacionados con las Neoplasias/genética , Lesiones Precancerosas/patología , Neoplasias Colorrectales/patología , Prevención de Enfermedades , Diagnóstico/prevención & control , Fenotipo , Herencia/genética , Inestabilidad Cromosómica/genética , Inestabilidad de Microsatélites , Literatura de Revisión como Asunto , Membrana Mucosa/anomalías , Metilación de ADN

RESUMEN

El cáncer colorrectal (CCR) es una de las principales causas de morbilidad y mortalidad a nivel mundial. Clásicamente se considera a los adenomas como las lesiones precursoras del CCR y se estipula un tiempo de 10 a 15 años para completar la secuencia adenoma-carcinoma. El CCR evoluciona a través de la acumulación progresiva de alteraciones genéticas y epigenéticas, las que conducen a la transformación de la mucosa colónica normal en cáncer invasivo. La identificación de diferentes vías moleculares de carcinogénesis colorrectal ha demostrado la naturaleza heterogénea del cáncer colónico.áDe reciente descripción, las lesiones aserradas muestran cambios moleculares y patológicos distintos a los adenomas tradicionales, estimándose que presentan un tiempo más acelerado de evolución hacia la malignidad. El objetivo de esta revisión es actualizar conocimientos sobre la génesis tumoral y sus bases biomoleculares a fin de posibilitar su aplicación a etapas clínicas concretas como la prevención y el tratamiento(AU)

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Colorectal cancer (CRC) is one of the main causes of morbidity and mortality worldwide. Adenomas are classically regarded as precursor lesions of CRC and between 10 and 15 years is thought to elapse to complete the adenoma-carcinoma sequence. CRC evolves through the progressive accumulation of genetic and epigenetic alterations that lead to invasive cancer through the transformation of normal colonic mucosa. The identification of different molecular pathways of colorectal carcinogenesis has demonstrated the heterogeneous nature of colon cancer. Recent description of serrated lesions shows molecular and pathological changes other than traditional adenomas with an estimated faster time of progression to malignancy. The aim of this review is to update the knowledge about tumorigenesis and its biomolecular basis for clinical application in early stages providing firm ground for prevention and treatment (AU)

Asunto(s)

Humanos , Adulto , Neoplasias Colorrectales/patología , Lesiones Precancerosas/patología , Epigénesis Genética/genética , Colonoscopía , Prevención de Enfermedades , Genes Relacionados con las Neoplasias/genética , Literatura de Revisión como Asunto , Fenotipo , Diagnóstico/prevención & control , Membrana Mucosa/anomalías , Metilación de ADN , Inestabilidad de Microsatélites , Inestabilidad Cromosómica/genética , Herencia/genética

RESUMEN

Endometriosis is a complex disease that has both benign and malignant characteristics. It affects 5-10% of women of reproductive age. Studies have demonstrated the existence of common genetic changes in endometriosis and ovarian cancer, suggesting a possible association between these 2 diseases. However, the mechanisms that lead to the development of cancer from endometriosis remain unknown. In this study, we evaluated 3 groups of women: 72 patients with endometriosis, 70 with ovarian cancer, and 70 healthy individuals (controls). Repair (XRCC1 codons 194 and 399, XPD codons 312 and 751, and XRCC3 codon 241)- and metabolism (BLHX codon 443)-related gene polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique; the efficiency of DNA damage repair was analyzed in vitro in lymphocytes exposed to bleomycin. The logistic regression model was used to evaluate key associations. The results showed an increased average of chromosome breakage in bleomycin-treated lymphocytes from patients with endometriosis and ovarian cancer compared with healthy women. We also detected significant association between XRCC1, XRCC3, and BLHX polymorphisms and a high frequency of chromosomal damage. Women with endometriosis or ovarian cancer may have an altered mechanism of DNA repair, and these defects may be related to a higher incidence of ovarian cancer.

Asunto(s)

Inestabilidad Cromosómica/genética , Cisteína Endopeptidasas/genética , Proteínas de Unión al ADN/genética , Endometriosis/genética , Neoplasias Ováricas/genética , Adulto , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Epidemiología Molecular , Neoplasias Ováricas/epidemiología , Polimorfismo de Nucleótido Simple , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X

RESUMEN

The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

Asunto(s)

Neoplasias Colorrectales/genética , Carcinogénesis/genética , Inestabilidad Cromosómica/genética , Metilación de ADN , Genes Supresores de Tumor , Humanos , MicroARNs/metabolismo , Inestabilidad de Microsatélites , Mutación , Proto-Oncogenes/genética

RESUMEN

Ataxia telangiectasia (AT) is a rare neurodegenerative disorder, inherited in an autosomal recessive manner. Total blood samples were collected from 20 patients with AT, 13 parents of patients, and 17 healthy volunteers. This study aimed at evaluating the frequency of chromosomal breaks in spontaneous cultures, induced by bleomycin and ionizing radiation, and further evaluated the rates of oxidative stress in AT patients and in their parents, compared to a control group. Three cell cultures were performed to each individual: the first culture did not receive induction to chromosomal instability, the second was exposed to bleomycin, and the last culture was exposed to ionizing radiation. To evaluate the rates of oxidative stress, the markers superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid (TBARS) were utilized. Significant differences were observed between the three kinds of culture treatments (spontaneous, bleomycin, and radiation induced) and the breaks and chromosomal aberrations in the different groups. The oxidative stress showed no significant differences between the markers. This study showed that techniques of chromosomal instability after the induction of ionizing radiation and bleomycin are efficient in the identification of syndrome patients, with the ionizing radiation being the most effective.

Asunto(s)

Ataxia Telangiectasia/genética , Inestabilidad Cromosómica/efectos de los fármacos , Inestabilidad Cromosómica/efectos de la radiación , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Adulto , Ataxia Telangiectasia/patología , Bleomicina/farmacología , Células Cultivadas , Inestabilidad Cromosómica/genética , Aberraciones Cromosómicas/efectos de los fármacos , Aberraciones Cromosómicas/efectos de la radiación , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/genética , Linaje , Radiación Ionizante

RESUMEN

BACKGROUND: The availability of a large number of recently sequenced vertebrate genomes opens new avenues to integrate cytogenetics and genomics in comparative and evolutionary studies. Cytogenetic mapping can offer alternative means to identify conserved synteny shared by distinct genomes and also to define genome regions that are still not fine characterized even after wide-ranging nucleotide sequence efforts. An efficient way to perform comparative cytogenetic mapping is based on BAC clones mapping by fluorescence in situ hybridization. In this report, to address the knowledge gap on the genome evolution in cichlid fishes, BAC clones of an Oreochromis niloticus library covering the linkage groups (LG) 1, 3, 5, and 7 were mapped onto the chromosomes of 9 African cichlid species. The cytogenetic mapping data were also integrated with BAC-end sequences information of O. niloticus and comparatively analyzed against the genome of other fish species and vertebrates. RESULTS: The location of BACs from LG1, 3, 5, and 7 revealed a strong chromosomal conservation among the analyzed cichlid species genomes, which evidenced a synteny of the markers of each LG. Comparative in silico analysis also identified large genomic blocks that were conserved in distantly related fish groups and also in other vertebrates. CONCLUSIONS: Although it has been suggested that fishes contain plastic genomes with high rates of chromosomal rearrangements and probably low rates of synteny conservation, our results evidence that large syntenic chromosome segments have been maintained conserved during evolution, at least for the considered markers. Additionally, our current cytogenetic mapping efforts integrated with genomic approaches conduct to a new perspective to address important questions involving chromosome evolution in fishes.

Asunto(s)

Cíclidos/genética , Citogenética/métodos , Evolución Molecular , Genómica/métodos , Animales , Inestabilidad Cromosómica/genética , Cromosomas Artificiales Bacterianos , Hibridación Fluorescente in Situ , Cromosomas Sexuales/genética

RESUMEN

Ski is a transcriptional regulator that has been considered an oncoprotein given its ability to induce oncogenic transformation in avian model systems. However, studies in mouse and in some human tumor cells have also indicated a tumor suppressor activity for this protein. We found that Ski-/- mouse embryo fibroblasts exhibit high levels of genome instability, namely aneuploidy, consistent with a tumor suppressor function for Ski. Time-lapse microscopy revealed lagging chromosomes and chromatin/chromosome bridges as the major cause of micronuclei (MN) formation and the subsequent aneuploidy. Although these cells arrested in mitosis after treatment with spindle disrupting drugs and exhibited a delayed metaphase/anaphase transition, spindle assembly checkpoint (SAC) was not sufficient to prevent chromosome missegregation, consistent with a weakened SAC. Our in vivo analysis also showed dynamic metaphase plate rearrangements with switches in polarity in cells arrested in metaphase. Importantly, after ectopic expression of Ski the cells that displayed this metaphase arrest died directly during metaphase or after aberrant cell division, relating SAC activation and mitotic cell death. This increased susceptibility to undergo mitosis-associated cell death reduced the number of MN-containing cells. The presented data support a new role for Ski in the mitotic process and in maintenance of genetic stability, providing insights into the mechanism of tumor suppression mediated by this protein.

Asunto(s)

Transformación Celular Neoplásica/genética , Inestabilidad Cromosómica/genética , Proteínas de Unión al ADN/genética , Fibroblastos/patología , Proteínas Proto-Oncogénicas/genética , Animales , Separación Celular , Células Cultivadas , Embrión de Mamíferos , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Immunoblotting , Ratones , Ratones Noqueados , Mitosis/genética , Transcripción Genética

RESUMEN

Here, we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos region using genome scanning, a microarray-based technique that delineates the majority of single-base changes, indels, and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon bears a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes, indicating mutations arising during self-mating or mitotic replication. The data also reveal that one or two meioses separate different isolates, showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pairwise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species, but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase of clindamycin EC(50) in strains harboring one of these mutations. This evidence of clindamycin-resistant parasites in the Amazon suggests that a shift should be made in health policy away from quinine + clindamycin therapy for malaria in pregnant women and infants, and that the development of new lincosamide antibiotics for malaria should be reconsidered.

Asunto(s)

Inestabilidad Cromosómica , Mapeo Cromosómico , Clindamicina , Resistencia a Medicamentos/genética , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Antimaláricos/uso terapéutico , Secuencia de Bases , Inestabilidad Cromosómica/genética , Mapeo Cromosómico/métodos , Clindamicina/uso terapéutico , Variaciones en el Número de Copia de ADN , Femenino , Frecuencia de los Genes , Genoma de Protozoos , Genotipo , Humanos , Lactante , Malaria Falciparum/diagnóstico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/genética , Masculino , Modelos Biológicos , Modelos Moleculares , Datos de Secuencia Molecular , Linaje , Perú , Embarazo , Telómero/genética

RESUMEN

Ring chromosomes are often associated with abnormal phenotypes due to loss of genomic material and also because of ring instability at mitosis after sister chromatid exchange events. We investigated ring chromosome instability in six patients with ring chromosomes 4, 14, 15, and 18 by examining 48- and 72-h lymphocyte cultures at the first, second and subsequent cell divisions after bromodeoxyuridine incorporation. Although most cells from all patients showed only one monocentric ring chromosome, ring chromosome loss and secondary aberrations were observed both in 48- and 72-h lymphocyte cultures and in metaphase cells of the different cell generations. We found no clear-cut correlation between ring size and ring instability; we also did not find differences between apparently complete rings and rings with genetic material loss. The cytogenetic findings revealed secondary aberrations in all ring chromosome patients. We concluded that cells with ring chromosome instability can multiply and survive in vivo, and that they can influence the patient's phenotype.

Asunto(s)

Inestabilidad Cromosómica/genética , Cromosomas en Anillo , Recuento de Células , Niño , Preescolar , Replicación del ADN , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Metafase , Embarazo

RESUMEN

The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were detected in eight patients, four de novo imbalances and four inherited from a normal parent. The de novo alterations define candidate chromosome segments likely to harbor dosage-sensitive genes related to hearing impairment, namely 1q23.3-q25.2, 2q22q23, 6p25.3 and 11q13.2-q13.4. The rare imbalances also present in normal parents might be casually associated with hearing impairment, but its role as a predisposition gene remains a possibility. Our results show that syndromic deafness is frequently associated with chromosome microimbalances (14-27%), and the use of aCGH for defining disease etiology is recommended.

Asunto(s)

Inestabilidad Cromosómica/genética , Pérdida Auditiva/genética , Niño , Preescolar , Hibridación Genómica Comparativa , Femenino , Dosificación de Gen , Humanos , Masculino , Síndrome

RESUMEN

We report a case of T-cell prolymphocytic leukemia (T-PLL) in a 41-year-old male. Classical cytogenetic, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies of a blood sample obtained at diagnosis revealed the co-existence of t(X;14)(q28;q11), t(Y;14)(q12;q11) and a ring chromosome derived from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8+. The co-existence of two translocations involving both sex chromosomes in a case of T-PLL is rare. Chromosomal instability associated with the disease progression may have allowed the emergence of cell clones with translocations involving the sex chromosomes and the ring chromosome observed.

Asunto(s)

Cromosomas Humanos Par 14/genética , Cromosomas Humanos X/genética , Cromosomas Humanos Y/genética , Leucemia Prolinfocítica de Células T/genética , Cromosomas en Anillo , Translocación Genética , Adulto , Inestabilidad Cromosómica/genética , Humanos , Masculino , Cariotipificación Espectral

RESUMEN

Con el objetivo de esclarecer la posible existencia de anomalías citogenéticas que aminoren la fertilidad del polen de Aloe vera, se analizó la etapa de proliferación celular que lleva a la formación de células madres del polen (CMPs). Se recolectaron botones florales (BF) en 25 plantas de una población ubicada a 10°34’15’’ N, 64°12’08’’ W, los cuales fueron fijados en Carnoy I por 24 h y almacenados en etanol (70 % v/v). Las observaciones se realizaron en preparaciones temporales obtenidas por la tinción del contenido de las anteras suspendidas en orceína acética (1.5 % p/v) por 5 minutos. De las 9 411 células analizadas, 17 % mostraron 1-8 puentes entre cromátidas hermanas, 13 % 1-7 micronúcleos de 0.9-4.8 µm, 8.1 % estaban unidas por puentes y 0.1 % no contenían cromatina. El resto de las células (61.8 %) presentó configuraciones aparentemente normales y sin variaciones morfométricas. La proliferación irregular de una fracción de CMPs (39.2 %) sugiere que las condiciones ambientales de la zona árida donde se realizaron los muestreos inducen inestabilidad cromosómica y cambios fisiológicos que afectan el normal desarrollo de la mitosis premeiótica, generando pérdida o adición de fragmentos, asociados a deficiencias y duplicaciones génicas.

Asunto(s)

Aloe/citología , Inestabilidad Cromosómica/genética , Cromosomas de las Plantas/genética , Mitosis/genética , Polen/citología , Células Madre/citología , Aloe/genética , Polen/genética , Venezuela

RESUMEN

In order to clarify possible cytogenetic anomalies that reduce pollen fertility, premeiotic mitosis was studied in Aloe vera plants from a naturalized population in the northeast of Venezuela (10 degrees 34' 15" N and 64 degrees 12' 08" W). Karyological configurations were evaluated during the stage of cell proliferation leading to the formation of pollen mother cells (PMCs). The sampling was carried out in March 2005, choosing inflorescences without mechanical or biological damage from 25 plants selected at random. Flower buds (FB) 2 to 6 mm in length were collected from 7:00 AM through 6:00 PM, their perianths removed, and fixed in Carnoy I (3:1 ethanol/glacial acetic acid) for 24 h and stored in ethanol (70% v/v) until observation. Light microscope observations were done on temporary preparations obtained by overflowing anther content suspended in acetic orcein (1.5% w/v) for 5 min and softly squashing with the cover slip. A total of 9 411 cells were analyzed. Upper mitotic activity was observed in FB from 3.8 +/- 0.09 mm long, collected at 11:00 AM through 1:00 PM; 17% of PMCs showed one to eight sister chromatid bridges from anaphase to telophase; 13%, one to seven micronucleus of variable diameter (0.9 to 4.8 microm); 8.1% were united by thin chromatin filaments, and 0.1% lacked a nucleus. Other evaluated cells (61.8%) had apparently normal mitotic configurations, without considerable morphometric variations. The evident irregular proliferation of a PMCs fraction (39.2%) suggests that environmental stress conditions (day temperatures ranging 32.7 to 39.8 degrees C, high solar radiation and low humidity) induce chromosome instability and physiologic changes that affect the normal development during premeiotic mitosis. As a consequence, loss or addition of chromosome fragments can occur in association with deficiencies and gene duplications.

Asunto(s)

Aloe/citología , Inestabilidad Cromosómica/genética , Cromosomas de las Plantas/genética , Mitosis/genética , Polen/citología , Células Madre/citología , Aloe/genética , Polen/genética , Venezuela

RESUMEN

The Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive disorder associated with microcephaly, immunodeficiency, chromosome instability and cancer proneness. The mutated gene that results in NBS codes for nibrin (Nbs1/p95), a DNA repair protein that is functionally linked to ATM, the kinase protein product of the gene responsible of ataxia-telangiectasia (A-T). We report the clinical, cytogenetic and molecular characterization of a second case of NBS in Chile detected by us. The patient is a 7 year old Chilean boy from a consanguineous marriage, with microcephaly, immunodeficiency and acute non lymphocytic leukemia (ANLL). As NBS shares chromosomal and cellular features with A-T, the cytogenetic studies of this patient also included 3 A-T patients. Our results showed that the frequency of spontaneous and X rays induced chromosomal aberrations in NBS are higher than in A-T cells. DNA analysis revealed that the patient is homozygous for the Slavic mutation 657del5 in the NBS1 gene. This finding and the absence of nibrin in patient's cells, confirmed the clinical diagnosis of NBS in our patient.

Asunto(s)

Inestabilidad Cromosómica/genética , Síndromes de Inmunodeficiencia/genética , Niño , Chile , Aberraciones Cromosómicas , Humanos , Masculino , Mutación , Linaje

RESUMEN

The rate of chromatid breaks was studied in cows with a history of sub-fertility by means of a test based on measurement of the average of breaks induced in lymphocytes of peripheral blood cultures. Fourteen female specimens were divided into two groups: fertile and sub-fertile. Peripheral blood lymphocytes were cultured and prepared for cytogenetic analysis. Two types of culture were established for each animal to evaluate the response of peripheral blood lymphocyte cultures to the genotoxic effects of bleomycin. The first culture did not receive bleomycin treatment (spontaneous chromosome aberrations). Our results showed that median breaks per cell (b/c) (+/-semirange) for spontaneous culture of the fertile and sub-fertile animals and bleomycin sensitivity assay for fertile and sub-fertile animals were 0.00+/-0.06, 0.02+/-0.03, 0.08+/-0.05 and 0.22+/-0.09, respectively. There was no significant difference (P>0.05) in the chromosomal breakage in lymphocytes not exposed to bleomycin; however, in comparing the number of chromatid breaks per cell in cultures treated with bleomycin, the sub-fertile group showed a significantly higher (P<0.05) level than the fertile group. These findings have implications both for identifying cattle with less than optimum fertility as well as for providing potential avenues to study the origins of sub-fertility.

Asunto(s)

Antibióticos Antineoplásicos/toxicidad , Bleomicina/toxicidad , Cromátides/efectos de los fármacos , Inestabilidad Cromosómica/efectos de los fármacos , Infertilidad Femenina/veterinaria , Animales , Bovinos , Inestabilidad Cromosómica/genética , Relación Dosis-Respuesta a Droga , Femenino , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/genética , Linfocitos/efectos de los fármacos

RESUMEN

In this study, we examine the morphology, mitotic stability, meiotic behavior and the composition of heterochromatin of B chromosomes in Cestrum intermedium and C. strigilatum. The results showed that B chromosome number shows intraindividual variation in the root meristem, which seems to lead to a slight rate of B elimination in this somatic tissue. B chromosomes in both species were similar in size and shape, but differed with regard to the type, size and distribution of heterochromatin. Possible evolutionary pathways for B chromosome origin in Cestrum are discussed.

Asunto(s)

Cestrum/genética , Bandeo Cromosómico/métodos , Cromosomas de las Plantas/genética , Inestabilidad Cromosómica/genética , Meiosis/genética , Metafase/genética , Semillas/genética

RESUMEN

In animals, supernumerary chromosomes and their evolution have mostly been studied in sexual reproducing species. In the present study, for the first time, the natural distribution and stability of supernumerary microchromosomes were investigated in the unisexual fish species Poecilia formosa. Natural habitats throughout the range of P. formosa were screened for the presence of microchromosomes over several years. A high frequency of microchromosomes was found in the Río Purificación river system. Evidence points to the presence of the same microchromosome lineage over many generations. No supernumerary chromosomes were found elsewhere than in the Río Purificación representing a significant difference in the distribution of microchromosome-bearing individuals between the Río Purificación and all other collection sites.

Asunto(s)

Inestabilidad Cromosómica/genética , Cromosomas de los Mamíferos/genética , Genética de Población/métodos , Poecilia/genética , Animales , Análisis Citogenético/métodos , ADN/genética , Dermatoglifia del ADN/métodos , Femenino , Masculino , Metafase/genética , México , Texas