RESUMEN
La citogenética es el estudio de los cromosomas tanto en número como en estructura. En 1882 Flemming publica las primeras primeras ilustraciones de los cromosomas humanos a partir de observaciones al microscopio y recién en el año 1953, Tjio y Levan determinaron el número real de cromosomas humanos por célula diploide (2n=46). El propósito de este trabajo es presentar el valor, uso actual e importancia de los estudios citogenéticos en aquellos casos en que el profesional de salud se enfrente a un paciente con una probable enfermedad de causa genética o síndrome dismórfico, además de exponer algunas experiencias de un laboratorio de Citogenética en el Paraguay, donde se realiza el estudio cromosómico. Aún con el advenimiento de la Biología Molecular y de la Citogenética Molecular, la citogenética convencional sigue siendo una herramienta de gran importancia, ya que permite realizar el diagnóstico de una enfermedad genética en pacientes con sospecha clínica de ser portadores de anomalías cromosómicas, y por tanto asesorar a las familias respecto de dicha enfermedad, proveer un pronóstico, riesgo de recurrencia y en casos que se requiera, un tratamiento(AU)
Cytogenetics is the study of chromosomes both in number and structure. The first publications about human cytogenetics were provided towards the end of the 19th century with the publication of Flemming in 1882 of the first figures of human chromosomes from observations under the microscope and only in 1953, Tjio and Levan determined the actual number of human chromosomes per diploid cell (2n = 46). The purpose of this paper is to present the value, current use and importance of cytogenetic studies in those cases in which the health professional faces a patient with a probable disease of genetic causes or dysmorphic syndrome, in addition to exposing some experiences from a Cytogenetics laboratory in Paraguay, where chromosomal study is carried out. Even with the arrival of Molecular Biology and Molecular Cytogenetics, conventional cytogenetics is a tool with a great importance, which allows the genetic disease diagnosis in patients with clinical suspicion of being carriers of chromosomal abnormalities, allowing to advice families about the disease, as well as to provide a prognosis, risk of recurrence and, in cases that requires it, a treatment(AU)
Asunto(s)
Humanos , Análisis Citogenético , Citogenética/tendencias , Enfermedades Genéticas Congénitas/diagnóstico , Cromosomas Humanos/genética , Cariotipo , MetafaseAsunto(s)
Humanos , Masculino , Secuencia Conservada , Cromosomas Humanos/genética , Metilación de ADN/genética , ADN Intergénico/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Próstata/metabolismo , Neoplasias de la Próstata/genética , Secuencia de Bases , Línea Celular Tumoral , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Células Epiteliales/metabolismo , Magnetismo , Hibridación de Ácido Nucleico , Sondas de Oligonucleótidos/genética , Estructura Terciaria de Proteína , Próstata/citología , Próstata/patología , Neoplasias de la Próstata/patología , Biomarcadores de Tumor/genéticaRESUMEN
AIMS AND OBJECTIVE: Primed in situ labeling/synthesis (PRINS) technique is an alternative to fluorescent in situ hybridization for chromosome analysis. This study was designed to evaluate the application of PRINS for rapid diagnosis of common chromosomal aneuploidy. MATERIALS AND METHODS: We have carried out PRINS using centromere specific oligonucleotide primers for chromosome X, Y, 13, 18 and 21 on lymphocyte metaphase and interphase cells spread. Specific primer was annealed in situ, followed by elongation of primer by Taq DNA polymerase in presence of labeled nucleotides. Finally, reaction was stopped and visualized directly under fluorescent microscope. RESULTS: Discrete centromere specific signals were observed with each primer. CONCLUSION: PRINS seems to be a rapid and reliable method to detect common chromosome aneuploidy in peripheral blood lymphocyte metaphase and interphase cells.
Asunto(s)
Aneuploidia/genética , Cromosomas Humanos/genética , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 21/genética , Humanos , Etiquetado in Situ Primed/métodos , Cromosoma X/genética , Cromosoma Y/genéticaRESUMEN
OBJETIVO: Caracterizar el ambiente genómico de las secuencias adyacentes al virus linfotrópico humano de células T tipo 1 (HTLV-1) en pacientes con paraparesia espßstica tropical y mielopatía asociada a la infección con HTLV-1 (PET/MAH) de diferentes regiones de Colombia y del Japón. MÉTODOS: Se enfrentaron 71 clones recombinantes con secuencias del genoma humano adyacentes al 5'-LTR de pacientes con PET/MAH, a las bases de datos del Genome Browser y del Gen-Bank. Se identificaron y analizaron estadísticamente 16 variables genómicas estructurales y composicionales mediante el programa informßtico R, versión 2.8.1, en una ventana de 0,5 Mb. RESULTADOS: El 43,0 por ciento de los provirus se localizaron en los cromosomas del grupo C; 74 por ciento de las secuencias se ubicaron en regiones teloméricas y subteloméricas (P < 0,05). Un anßlisis de conglomerados permitió establecer las relaciones jerßrquicas entre las características genómicas incluidas en el estudio; el anßlisis de componentes principales identificó las componentes que definieron los ambientes genómicos preferidos para la integración proviral en casos de PET/MAH. CONCLUSIONES: El HTLV-1 se integró con mayor frecuencia en regiones de la cromatina ricas en islas de citocina fosfato guanina (CpG), de alta densidad de genes y de repeticiones tipo LINE (elemento disperso largo [long interspersed element]) y transposones de ADN que, en conjunto, conformarían los ambientes genómicos blanco de integración. Este nuevo escenario promoverß cambios sustanciales en el campo de la salud pública y en el manejo epidemiológico de las enfermedades infecciosas, y permitirß desarrollar potentes herramientas para incrementar la eficiencia de la vigilancia epidemiológica.
OBJECTIVE: Characterize the genomic environment of the sequences adjacent to human T-cell lymphotropic virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in different regions of Colombia and Japan. METHODS: A total of 71 recombinant clones with human genome sequences adjacent to 5' LTR in patients with HAM/TSP were compared to the Genome Browser and GenBank databases. Sixteen structural and compositional genome variables were identified, and statistical analysis was conducted in the R computer program, version 2.8.1, in a 0.5 Mb window. RESULTS: A total of 43.0 percent of the proviruses were located in the group C chromosomes; 74 percent of the sequences were located in the telomeric and subtelomeric regions (P < 0.05). A cluster analysis was used to establish the hierarchical relations between the genome characteristics included in the study. The analysis of principal components identified the components that defined the preferred genome environments for proviral integration in cases of HAM/TSP. CONCLUSIONS: HTLV-1 was integrated more often in chromatin regions rich in CpG islands with a high density of genes and LINE type repetitions, and DNA transposons which, overall, would form the genomic environments targeted for integration. This new scenario will promote substantial changes in the field of public health and in epidemiological management of infectious diseases. It will also foster the development of powerful tools for increasing the efficiency of epidemiological surveillance.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Genoma Humano , Virus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/genética , Provirus/genética , Secuencias Repetidas Terminales/genética , Integración Viral/genética , Mapeo Cromosómico , Cromosomas Humanos/genética , Colombia/epidemiología , Islas de CpG , ADN Recombinante/genética , Paraparesia Espástica Tropical/epidemiología , Paraparesia Espástica Tropical/virología , Retroelementos/genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido NucleicoRESUMEN
OBJECTIVE@#To introduce the method of avuncular index (AI) calculation.@*METHODS@#Identity by decent coefficient, coancestry coefficient and AI law were employed in identification of uncle-niece relationship, when autosomal STR loci were detected to determine controversial uncle-niece relationship.@*RESULTS@#The results of AI calculation were coincidental using identity by descent coefficien, coancestry coefficient and AI law.@*CONCLUSION@#The results are coincidental using three methods in the different situations. AI index is higher with participation of children's mother.
Asunto(s)
Femenino , Humanos , Masculino , Algoritmos , Alelos , Cromosomas Humanos/genética , Familia , Genética Forense/métodos , Genotipo , Heterocigoto , Modelos Genéticos , Paternidad , Probabilidad , Secuencias Repetidas en Tándem/genéticaRESUMEN
Alu family is the primate specific short interspersed repetitive elements (SINEs). Its abundance and diversity distribution in genome, high methylation level and polymorphic for insertion make them ideally suitable as tools in forensic applications. The application of A4 lu sequence in forensic genomics, include DNA quantitation, race determination, species and gender identification, personal identification, paternity testing and whole-genome amplification. The principles and characteristics of these Alu-based techniques are also summarized. The prospect of Alu as forensic molecular marker is discussed as well.
Asunto(s)
Humanos , Elementos Alu/genética , Secuencia de Bases , Cromosomas Humanos/genética , ADN/genética , Metilación de ADN , Genética Forense/métodos , Marcadores Genéticos , Genoma Humano , Reacción en Cadena de la Polimerasa , Polimorfismo Genético/genética , Sensibilidad y Especificidad , Análisis de Secuencia de ADNRESUMEN
Recently, microarray-based comparative genomic hybridization (array-CGH) has emerged as a very efficient technology with higher resolution for the genome-wide identification of copy number alterations (CNA). Although CNAs are thought to affect gene expression, there is no platform currently available for the integrated CNA-expression analysis. To achieve high-resolution copy number analysis integrated with expression profiles, we established human 30k oligoarray-based genome-wide copy number analysis system and explored the applicability of this system for integrated genome and transcriptome analysis using MDA-MB-231 cell line. We compared the CNAs detected by the oligoarray with those detected by the 3k BAC array for validation. The oligoarray identified the single copy difference more accurately and sensitively than the BAC array. Seventeen CNAs detected by both platforms in MDA-MB-231 such as gains of 5p15.33-13.1, 8q11.22-8q21.13, 17p11.2, and losses of 1p32.3, 8p23.3-8p11.21, and 9p21 were consistently identified in previous studies on breast cancer. There were 122 other small CNAs (mean size 1.79 mb) that were detected by oligoarray only, not by BAC-array. We performed genomic qPCR targeting 7 CNA regions, detected by oligoarray only, and one non-CNA region to validate the oligoarray CNA detection. All qPCR results were consistent with the oligoarray-CGH results. When we explored the possibility of combined interpretation of both DNA copy number and RNA expression profiles, mean DNA copy number and RNA expression levels showed a significant correlation. In conclusion, this 30k oligoarray-CGH system can be a reasonable choice for analyzing whole genome CNAs and RNA expression profiles at a lower cost.
Asunto(s)
Femenino , Humanos , Neoplasias de la Mama/genética , Cromosomas Artificiales Bacterianos , Cromosomas Humanos/genética , Hibridación Genómica Comparativa , Dosificación de Gen/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genoma Humano , Hibridación Fluorescente in Situ , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , ARN Neoplásico/genética , Células Tumorales CultivadasRESUMEN
PURPOSE: Genetic factors are known to be important in the etiology of bipolar disorder (BD). The fragile sites (FSs) are a very interesting subject for the study of clinical disorders. The aim of this study was to evaluate fragile sites seen in patients with bipolar disorder and find a correlation between some fragile sites and bipolar disorder. PATIENTS AND METHODS: The frequencies of folate sensitive FSs were compared in short-term whole blood cultures from bipolar patients and from normal individuals. RESULTS: The rate of FS expression in the patients was considerably higher than in the controls (p < 0.001). Several chromosome regions including 1p36, 1q21, 1q32, 3p25, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22 and Xq26 were represented considerably more often in the patients than in the controls (p value between 0.001 to 0.036). Among these FSs, the sites 1p36, 1q21, 3p25, 7q22, 7q32, and 14q24 were not observed in other studies. CONCLUSION: These regions can be the most active of hot spots in the genomes of bipolar patients, and may harbor important genes associated with BD.
Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Trastorno Bipolar/genética , Sitios Frágiles del Cromosoma/efectos de los fármacos , Fragilidad Cromosómica/efectos de los fármacos , Cromosomas Humanos/genética , Citogenética , Ácido Fólico/farmacología , Predisposición Genética a la EnfermedadRESUMEN
The QTc interval is a complex quantitative trait and a strong prognostic indicator of cardiovascular mortality in general, healthy people. The aim of this study was to identify non-genetic factors and quantitative trait loci that govern the QTc interval in an isolated Mongolian population. We used multiple regression analysis to determine the relationship between the QTc interval and non-genetic factors including height, blood pressure, and the plasma lipid level. Whole genome linkage analyses were performed to reveal quantitative trait loci for the QTc interval with 349 microsatellite markers from 1,080 Mongolian subjects. Among many factors previously known for association with the QTc interval, age, sex, heart rate, QRS duration of electrocardiogram and systolic blood pressure were also found to have influence on the QTc interval. A genetic effect for the QTc interval was identified based on familial correlation with a heritability value of 0.31. In a whole genome linkage analysis, we identified the four potential linkage regions 7q31-34, 5q21, 4q28, and 2q36.
Asunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Edad , Presión Sanguínea/genética , Estatura/genética , Enfermedades Cardiovasculares/genética , Cromosomas Humanos/genética , Electrocardiografía , Estudio de Asociación del Genoma Completo , Frecuencia Cardíaca/genética , Repeticiones de Microsatélite/genética , Mongolia/epidemiología , Sitios de Carácter Cuantitativo/genética , Factores SexualesAsunto(s)
Niño , Cromosomas Humanos/genética , Síndrome de Down/genética , Femenino , Humanos , India , Recién Nacido , Cariotipificación , Fenotipo , Trisomía/genéticaRESUMEN
A new door has been opened to health professionals since the completion of the map of the human genome was announced in 2003, coinciding with the 50th anniversary of the discovery of the DNA helical structure by Watson and Crick in 1953. The continuous updating of the technology has enabled scientists to simultaneously analyze thousands of variables for genome analysis. These advances have created new opportunities to locate genes, to assess the gene-gene relationship, to measure the gene-environment interaction, to describe gene products, and to evaluate the gene-disease relationship. In epidemiology, new strategies have been developed to determine cause-effect relationship in case-control studies and cohort studies. With the information provided by the Human Genome Project, new epidemiological designs and new statistical methodology have been developed. The addition of molecular biology to traditional epidemiological approaches has given birth to a new discipline known as genetic epidemiology. The objective of this paper is to provide an introduction to concepts needed for assessing the association between genes and specific diseases in population based studies. Firstly, a description of the genetic concepts is presented as a framework for the epidemiological designs and the statistical procedures that have been utilized in genetic epidemiology. Then, a description of the different designs in genetic epidemiology is presented with the most recent publications. Finally, some considerations in the statistical analysis for genetic epidemiology are discussed.
Asunto(s)
Humanos , Epidemiología , Genética , Modelos Estadísticos , Mapeo Cromosómico , Cromosomas Humanos/genética , Genes/genética , Biología Molecular , MutaciónRESUMEN
Suitability of a specific population for linkage disequilibrium mapping studies of complex traits may be assessed by investigating the background linkage disequilibrium (BLD). We are unaware of studies for quantifying the degree of BLD in the Korean population, although the population may be a good candidate for mapping of complex trait genes through whole-genome association studies. It is useful to investigate the properties of genetic isolates in East Asia and to compare them to genetic isolates in Europe. We analyzed the extent of BLD in the Korean population using 735 microsatellite markers and compared the results with the Icelander population, which is one of the European expanded genetic isolates. The Korean population exhibited a level of BLD comparable with the Icelander population. The inference of population structure using the model with admixture showed that each individual has allele copies originating from K populations in equal proportions. Therefore, we believe that factors other than genetic distance, such as recent admixture, have not contributed to the level of BLD. Our results showed that the Korean population, which is an expanded population with no evidence of admixture, has a BLD level comparable with the Icelander population. Therefore, the Korean population can be used for fine mapping of either complex traits or monogenic diseases.
Asunto(s)
Masculino , Humanos , Femenino , Adulto , Repeticiones de Microsatélite/genética , Desequilibrio de Ligamiento/genética , Corea (Geográfico) , Heterocigoto , Cromosomas Humanos/genéticaRESUMEN
In the pathogenesis of cervical cancer the role of human papillomavirus (HPV) infection is well established. However, other than HPV infection the genetics of cervical cancer remains poorly understood. In the pathogenesis of cervical cancel three major factors are involved, two of which are related to the presence of HPV and the third is the recurrent genetic alterations not linked to HPV infection. Several chromosomal regions with recurrent loss of heterozygosity (LOH) in cervical cancer have been identified. However; the putative tumor suppressor genes located in these chromosomal locations are yet to be identified. Recurrent amplifications have been mapped to the short arm of chromosome 3 in invasive cancer. Microsatellite instability and mutator phenotype do not play a major role in cervical carcinogenesis. As in other cancers, cervical cancer too requires the accumulation of genetic alterations for carcinogenesis to occur. Identification of these alterations could help to provide a better understanding of the disease and thus improve treatment.
Asunto(s)
Cromosomas Humanos/genética , ADN Viral/genética , Femenino , Humanos , Pérdida de Heterocigocidad/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Mutación Puntual , Factores de Riesgo , Neoplasias del Cuello Uterino/etiologíaRESUMEN
Schizophrenia is a severe neuropsychiatric disorder with a polygenic mode of inheritance which is also governed by non-genetic factors. Candidate genes identified on the basis of biochemical and pharmacological evidence are being tested for linkage and association studies. Neurotransmitters, especially dopamine and serotonin have been widely implicated in its etiology. Genome scan of all human chromosomes with closely spaced polymorphic markers is being used for linkage studies. The completion and availability of the first draft of Human Genome Sequence has provided a treasure-trove that can be utilized to gain insight into the so far inaccessible regions of the human genome. Significant technological advances for identification of single nucleo-tide polymorphisms (SNPs) and use of microarrays have further strengthened research methodologies for genetic analysis of complex traits. In this review, we summarize the evolution of schizophrenia genetics from the past to the present, current trends and future direction of research.
Asunto(s)
Anticipación Genética , Catecol O-Metiltransferasa/genética , Cromosomas Humanos/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Genoma Humano , Historia del Siglo XX , Humanos , India , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana/genética , Biología Molecular , Monoaminooxidasa/genética , Proteínas del Tejido Nervioso , Polimorfismo de Nucleótido Simple/genética , Receptores Dopaminérgicos/genética , Receptores de Serotonina/genética , Esquizofrenia/genética , Tirosina 3-Monooxigenasa/genéticaRESUMEN
The major aneuploidies diagnosed prenatally involve the autosomes 13, 18, 21, and sex chromosomes X and Y. Fluorescence in situ hybridization (FISH) allows rapid analysis of chromosome copy number in interphase cells. We retrospectively reviewed 130 amniotic fluid interphase FISH analyses from January 1997 to December 2001. The review was done in order to assess the role of interphase FISH among the patients who were at the risk of fetal aneuploidies. The sample was considered to be aneuploid when 70% of or more than the total number of hybridized nuclei displayed the same abnormal hybridization pattern for a specific probe. All of 130 cases but one met the criteria. The results were considered as informative and they were obtained in 24-48 hr. The overall detection rate for aneuploidies was 100% (2 cases of trisomy 21, 2 cases of trisomy 18, and 1 case of Turner syndrome). In comparison to cytogenetics, the rates of both sensitivity and specificity were 100%. The experiment demonstrates that FISH can provide a rapid and accurate clinical method for prenatal identification of chromosome aneuploidies. The experiment can also serve as an adjunctive test to help cytogenetics to reduce significant amount of emotional stress of patients and physicians through early decision making process.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Embarazo , Amniocentesis , Líquido Amniótico/citología , Aneuploidia , Cromosomas Humanos/genética , Hibridación Fluorescente in Situ/métodos , Interfase , Diagnóstico Prenatal/métodos , Estudios Retrospectivos , Factores de TiempoAsunto(s)
Humanos , Catalasa/genética , Enzimas/farmacocinética , Genoma Humano , Glutatión Peroxidasa/genética , Glutatión Sintasa/genética , Superóxido Dismutasa/genética , Antioxidantes/farmacocinética , Cromosomas Humanos/efectos de los fármacos , Cromosomas Humanos/enzimología , Cromosomas Humanos/genética , Monoaminooxidasa/genética , NADP/genética , Oxidantes/antagonistas & inhibidores , Óxido Nítrico Sintasa/genética , Peroxidasa/genética , Xantina Deshidrogenasa/genéticaRESUMEN
Introducción. El intercambio entre cromátides hermanas (ICH) es un evento celular normal, con frecuencia basal relativamente constante de ICH espontáneos por metafase, variable en células de tejidos diferentes. Factores individuales y por proceso de laboratorio pueden hacer variar la frecuencia basal de ICH. La exposición a agentes clastogénicos es capaz de incrementarla. En este trabajo se describe la prevalencia de ICH en una población libre de exposición a agentes clastogénicos conocidos. Material y métodos. Se incluyó 50 individuos sanos de uno u otro sexo, de 10 a 59 años. A cada uno se les realizó dos cultivos de sangre, a los que se agregó bromodeoxiuridina a las 0 y 24 h respectivamente, para la obtención de metafases con tinción diferencial de cromátides. De cada cultivo se analizaron 25 metafases para determinar el promedio del ICH/células/individuo. Resultados el promedio de ICH/célula/individuo en los cultivos de 0 y 24 h fue 4.21ñ1.20 y 3.9ñ0.94 respectivamente, con intervalo y DE de 2.12ñ1.12 a 7.4ñ3.31 en los cultivos de 0 h. En los cultivos de 24 h el intervalo y DE encontrados fueron de 2.12ñ1.3 a 7.08ñ2.75. La diferencia entre los dos cultivos no fue significativa (p<0.10). El grupo de edad con mayor número de ICH fue de 20 a 29 años, sin encontrarse diferencias significativas entre cada decenio de edad. Tampoco se encontró diferencias significativas entre géneros. Discusión. Los resultados encontrados son similares a los encontrados en otras poblaciones, a excepción del decenio de edad con el pico máximo de ICH. Estos resultados permiten tener confiabilidad en el procedimiento utilizado
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Bromodesoxiuridina , Cromosomas Humanos/genética , Citogenética , Metafase , Mutágenos , Intercambio de Cromátides Hermanas , PrevalenciaRESUMEN
Las terasomías del cromosoma X son complementos cromosómicos raros no asociados a un cuadro clínico específico pero la mayoría de los pacientes con esta polisomía del X presentan retardo en el aprendizaje, inmadurez emocional y disfunción gonadal. En el presente trabajo, se describen los hallazgos clínicos y citogenéticos en una paciente con amenorrea primaria, retardo psicomotor, inmadurez emocional y cariotipo 48, XXXX, inv (9). Aunque es difícil correlacionar los cromosomas X supernumerarios en esta paciente con la inversión del cromosoma 9 heredada del padre, el presente caso parece ser, hasta donde sabemos, la primera tetrasomía del X asociada a una inversión pericentromérica del cromosoma 9. Las tetrasomías del X podrían originarse por dos errores no-disyuncionales sucesivos ocurridos posiblemente en la gametogénesis materna