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1.
Med. infant ; 30(2): 168-171, Junio 2023.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1443722

ABSTRACT

Las técnicas de Biología Molecular de última generación, como es la secuenciación masiva en paralelo o NGS (Next Generation Sequencing), permite obtener gran cantidad de información genómica, la cual muchas veces va más allá de la detección de una variante patogénica en un gen que explique la patología (hallazgo primario). Es así como surgió desde hace años la discusión internacional respecto a la decisión a tomar frente a los hallazgos secundarios accionables, es decir, aquellos hallazgos de variantes clasificadas como patogénicas o probablemente patogénicas que no están relacionadas con el fenotipo del paciente, pero que tiene alguna medida preventiva o tratamiento posible y, por lo tanto, podría ser de utilidad para la salud del paciente. Luego de revisar la bibliografía internacional y debatir entre los expertos del Hospital de Pediatría Garrahan, se logró establecer una política institucional y reforzar el hecho de que se trata de una disciplina multidisciplinaria. Así, fue posible definir que solo se atenderá las cuestiones relacionadas con la edad pediátrica, dejando para un tratamiento posterior aquellas variantes detectadas en genes que sean accionables en edad adulta. En el Hospital Garrahan, ha sido posible definir claramente cómo proceder frente a los hallazgos secundarios, al adaptar el consentimiento informado a esta necesidad, definiendo cuándo serán informados, y sabiendo que serán buscados intencionalmente en los genes clínicamente accionables enlistados en la última publicación del American College of Medical Genetics and Genomics, siempre y cuando el paciente/padre/tutor lo consienta (AU)


The latest generation of molecular biology techniques, including massive parallel sequencing or NGS (Next Generation Sequencing), allows us to obtain a whealth of genomic information, which often goes beyond the detection of a pathogenic variant in a gene that explains the pathology (primary finding). As a result, an international discussion has arisen over the years regarding the decision-making concerning actionable secondary findings, it means, those findings of variants classified as pathogenic or probably pathogenic that are not related to the patient's phenotype, but which have some possible preventive measure or treatment and, therefore, could be useful for the patient's health. After reviewing the international literature and discussing among the experts of the Hospital de Pediatría Garrahan, an institutional policy was established and the concept that this is a multidisciplinary discipline was reinforced. Consequently, it has been defined that only issues related to children will be addressed, reserving those variants detected in genes that are actionable in adulthood for later treatment. At Garrahan Hospital, we were able to clearly define how to proceed with secondary findings by adapting the informed consent to this need, defining when they will be reported, and knowing that they will be intentionally searched for in the clinically actionable genes listed in the latest publication of the American College of Medical Genetics and Genomics, as long as the patient/parent/guardian consents (AU)


Subject(s)
Humans , Genome, Human/genetics , Incidental Findings , High-Throughput Nucleotide Sequencing , Genomic Medicine/trends , Hospitals, Pediatric , Molecular Biology/trends , Informed Consent
2.
Chinese Journal of Medical Genetics ; (6): 915-921, 2023.
Article in Chinese | WPRIM | ID: wpr-1009234

ABSTRACT

ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2020, a supplementary practical guidelines, is based on the Standards and Guidelines for the Interpretation of Sequence Variations issued by the American Society for Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP) in 2015 by the British Medical Genetics Society under the Clinical Genomics Society (ACGS), and has integrated the detailed rules of standards developed by the ClinGen Sequence Variant Interpretation (SVI) Working Group by 2020. The further development of the ACMG/AMP guidelines is currently undertaken by the ClinGen SVI working group in the United States, which focuses on the classification of high penetrance and protein coding variants. ClinGen has established many expert panels on variants for specific diseases which required various evidence thresholds and is currently developing disease/gene specific guidelines. The British Medical Genetics Society has collected and integrated information on the guidelines for sequence variation classification and their extended rules, forming its own "2020 ACGS Best Practice Guidelines for Rare Disease Variation Classification" and is regularly updating it. The author has translated and summarized it for the reference of Chinese Medical Genetics Practitioners.


Subject(s)
Humans , Genetic Testing , Genetic Variation , Genome, Human , Rare Diseases/genetics , China
3.
Montevideo; [s.n.]; 2023. 109 p. ilus.
Monography in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1524295
5.
Chinese Journal of Medical Genetics ; (6): 1-10, 2022.
Article in Chinese | WPRIM | ID: wpr-928350

ABSTRACT

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.


Subject(s)
Child , Female , Humans , Pregnancy , DNA Copy Number Variations , Genetic Testing , Genetics, Medical , Genome, Human/genetics , Genomics , United States
6.
Arq. Asma, Alerg. Imunol ; 5(3): 237-245, jul.set.2021. ilus
Article in Portuguese | LILACS | ID: biblio-1399212

ABSTRACT

Asma é uma denominação única para um conjunto de disfunções respiratórias que se expressam, clinicamente, por episódios repetidos, com intensidade variável de dispneia, sibilos, tosse e opressão torácica. A variação entre suas formas clínicas é resultante da participação e interação entre fatores genéticos, microbiômicos e ambientais. O progresso na área médica, ao incorporar novos recursos tecnológicos da biociência e bioinformática, vem desvendando a intimidade dos processos genéticos e moleculares envolvidos nos diferentes mecanismos patogênicos presentes na asma. Isso vem levando à identificação de novos alvos terapêuticos e à pesquisa de novos agentes medicamentosos. Ao mesmo tempo, a perspectiva de inserção paulatina desses recursos no cotidiano médico tem promovido mudanças na prática médica, que vem adotando os princípios da medicina de precisão. Possivelmente, estas mudanças melhorarão o horizonte dos asmáticos, uma população ainda desprovida de instrumentos terapêuticos totalmente efetivos.


Asthma is a unique designation for a set of respiratory dysfunctions clinically expressed by repeated episodes of varying intensity of dyspnea, wheezing, cough, and chest oppression. The variation between its clinical forms is the result of the participation and interaction between genetic, microbiomic, and environmental factors. Progress in the medical field, with incorporation of new technological resources from bioscience and bioinformatics, has been unveiling the intimacy of genetic and molecular processes involved in the different pathogenic mechanisms present in asthma. This has led to the identification of new therapeutic targets and the search for new therapeutic agents. At the same time, the perspective of gradual insertion of these resources in daily medical activities has been promoting changes in medical practice, which has been adopting the principles of precision medicine. Possibly, these changes will provide a better future for asthmatic patients, a population still devoid of fully effective therapeutic instruments.


Subject(s)
Humans , Asthma , Precision Medicine , Microbiota , Patients , Research , Therapeutics , Genome, Human , Respiratory Sounds , Cough , Dyspnea , Genetic Phenomena , Health Resources
7.
Rev. Hosp. Ital. B. Aires (2004) ; 41(1): 37-42, mar. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1178964

ABSTRACT

El término CRISPR, por su acrónimo en inglés refiere a Clustered Regularly Interspaced Short Palindromic Repeats, es decir, repeticiones palindrómicas cortas, agrupadas y regularmente esparcidas, por sus características en el genoma, pertenece naturalmente al sistema de defensa de bacterias y arqueas. Este ha sido adaptado biotecnológicamente para la edición del ADN de células eucariotas, incluso de células humanas. El sistema CRISPR-Cas para editar genes consta, en forma generalizada, de dos componentes: una proteína nucleasa (Cas) y un ARN guía (sgRNA). La simplicidad del complejo lo hace una herramienta molecular reprogramable capaz de ser dirigida y de editar cualquier sitio en un genoma conocido. Su principal foco son las terapias para enfermedades hereditarias monogénicas y para el cáncer. Sin embargo, además de editor de genes, la tecnología CRISPR se utiliza para edición epigenética, regulación de la expresión génica y método de diagnóstico molecular. Este artículo tiene por objetivo presentar una revisión de las aplicaciones de la herramienta molecular CRISPR-Cas, particularmente en el campo biomédico, posibles tratamientos y diagnósticos, y los avances en investigación clínica, utilizando terapia génica con CRISPR/Cas más relevantes hasta la fecha. (AU)


CRISPR are Clustered Regularly Interspaced Short Palindromic Repeats, which naturally belong to the defense system of bacteria and archaea. It has been biotechnologically adapted for editing the DNA of eukaryotic cells, including human cells. The CRISPR-Cas system for editing genes generally consists of two components, a nuclease protein (Cas) and a guide RNA (sgRNA). The simplicity of the complex makes it a reprogrammable molecular tool capable of being targeted and editing any site in a known genome. Its main focus is therapies for monogenic inherited diseases and cancer. However, in addition to gene editor, CRISPR technology is used for epigenetic editing, regulation of gene expression, and molecular diagnostic methods. This article aims to present a review of the applications of the CRISPR-Cas molecular tool, particularly in the biomedical field, possible treatments and diagnoses, and the advances in clinical research, using the most relevant CRISPR-Cas gene therapy to date. (AU)


Subject(s)
Humans , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , CRISPR-Cas Systems/genetics , Biotechnology , Genetic Therapy/methods , Gene Expression , Genome, Human/genetics , Gene Expression Regulation , Epigenomics/trends , CRISPR-Associated Proteins/genetics , CRISPR-Associated Proteins/therapeutic use , Genetic Diseases, Inborn/therapy , Neoplasms/therapy
8.
Rev. colomb. psiquiatr ; 50(1): 57-63, Jan.-Mar. 2021. tab
Article in Spanish | LILACS, COLNAL | ID: biblio-1251635

ABSTRACT

RESUMEN El presente artículo es el resultado de una investigación, desde las perspectivas bioética y biojurídica, acerca de los lineamientos existentes en Colombia para el manejo de las pruebas farmacogenómicas y farmacogenéticas en los ensayos clínicos. La revisión de la legislación existente en nuestro medio se comparó con estándares internacionales y los propuestos por organismos supranacionales. Se encontró que en Colombia falta una regulación específica en esta área, lo que expone a una serie de riesgos bioéticos y jurídicos a los participantes e investigadores. No se deben subestimar estos riesgos, pues comprometen la viabilidad ética de la investigación clínica y básica en nuestro medio. Al final, desde la perspectiva de la ética de los principios, se proponen una serie de acciones para la creación y la promoción a escala nacional de lineamientos que sirvan para conformar una legislación aplicable a la protección de los datos genéticos y, por ende, los derechos de los sujetos que participan en esta clase de estudios de investigación en Colombia.


ABSTRACT This paper is the result of research, from the bioethics and bio-legal perspectives, on the existing guidelines in Colombia for the handling of pharmacogenomic and pharmacogenetic tests in clinical trials. Colombian legislation on this kind of research was reviewed and then compared with international and supranational standards. It was found that Colombia lacks specific legislation in this area, a situation that puts both participants and researchers at risk, from bioethical and legal perspectives. These risks should not be underestimated, as they compromise the ethical viability of clinical and basic research in our setting. In the end, a proposal, based on principles of ethics is made, proposing a series of actions for the creation and promotion nationwide of guidelines which can be used to shape legislation to be applied to protect the genetic data and the rights of subjects participating in these types of research studies in Colombia.


Subject(s)
Humans , Bioethics , Pharmacogenomic Testing , Psychiatry , Research , Social Control, Formal , Genome, Human , Colombia , Ethics, Research , Research Subjects
9.
Rev. cuba. pediatr ; 92(4): e918, oct.-dic. 2020. tab, graf
Article in English | LILACS, CUMED | ID: biblio-1144519

ABSTRACT

Introduction: Neurodevelopmental disorders (NDD) are featured by a delay in the acquisition of motor functions, cognitive abilities and speech, or combined deficits in these areas with the onset before the age of 5 years. Genetic causes account for approximately a half of all NDD cases. Objective: to describe alterations of the genome implied in neurodevelopmental disorders and some aspects of their genetic counseling. Methods: Bibliographic search in Medline, Pubmed, Scielo, LILACS and Cochrane, emphasizing in the last five years, the relationship between the various genetic factors that may be involved in neurodevelopmental disorders. Results: Multiple genetic factors are involved in neurodevelopmental disorders, from gross ones such as chromosomal aneuploidies to more subtle ones such as variations in the number of copies in the genome. Special emphasis is placed on microdeletion-micro duplication syndromes as a relatively frequent cause of NDDs and their probable mechanisms of formation are explained. Final Considerations: Genetic aberrations are found in at least 30-50 percent of children with NDD. Conventional karyotyping allows the detection of chromosomal aberrations encompassing more than 5-7 Mb, which represent 5-10 percent of causative genome rearrangements in NDD. Molecular karyotyping (e.g. SNP array/array CGH) can significantly improve the yield in patients with NDD and congenital malformations(AU)


Introducción: Los trastornos del neurodesarrollo están caracterizados por retardo en la adquisición de las funciones motoras, habilidades cognitivas para el habla o el déficit combinado en estas áreas; se presenta en niños menores de 5 años de edad. Las causas genéticas están implicadas en más de la mitad de los pacientes con estos trastornos Objetivo: Examinar las alteraciones del genoma implicados en los trastornos del neurodesarrollo y algunos aspectos de su asesoramiento genético. Métodos: Búsqueda bibliográfica en Medline, Pubmed, Scielo, LILACS y Cochrane con énfasis en los últimos cinco años, acerca de la relación entre los variados factores genéticos que pueden estar involucrados en los trastornos del neurodesarrollo. Resultados: Los factores genéticos involucrados pueden ser groseros como las aneuploidías cromosómicas hasta los más sutiles como las variaciones en el número de copias en el genoma. Se describen los síndromes de microdeleción-micro duplicación como una causa relativamente frecuente de los trastornos del neurodesarrollo y se explican sus probables mecanismos de formación. Se relacionan las aneuploidías cromosómicas y las variaciones en el número de copia como causas de estos trastornos. Consideraciones finales . Las aberraciones genéticas se encuentran en 30-50 por ciento de los niños con trastornos del neurodesarrollo. El cariotipo convencional permite la detección de aberraciones cromosómicas que abarcan más de 5-7 Mb, lo que representa 5-10 por ciento de los reordenamientos genómicos causales en estos trastornos. El cariotipo molecular (por ejemplo, una matriz de SNP/ CGH de matriz) puede mejorar significativamente la certeza del diagnóstico en pacientes con trastornos del neurodesarrollo y malformaciones congénitas(AU)


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Chromosome Aberrations , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/epidemiology , Genome, Human/genetics
11.
Fractal rev. psicol ; 32(2): 111-119, maio-ago. 2020. tab
Article in Portuguese | INDEXPSI, LILACS | ID: biblio-1133939

ABSTRACT

Este trabalho problematiza os pressupostos ontológicos assumidos no debate bioético sobre a seleção e edição do genoma humano. Com vistas ao manejo de desordens genéticas, diferentes terapêuticas têm sido empregadas clínica e experimentalmente, desde a década de 1990. Entre as estratégias de tratamento destacam-se a seleção de embriões (mediante diagnóstico genético pré-implantação) e a terapia gênica (mediante edição genética). O desenvolvimento destas técnicas suscita discussões acerca de suas implicações éticas. O presente artigo postula que distintas concepções de humanidade podem ser identificadas nas discussões, as quais fundamentam posicionamentos acerca de intervenções sobre o genoma da espécie. O artigo busca analisar essas concepções, percorrendo três passos. Primeiramente, apresenta-se o contexto biomédico de aplicação da seleção e edição do genoma humano. Em seguida, são evidenciadas discussões sobre os aspectos éticos de tais intervenções. Por fim, explicitam-se diferentes concepções de humanidade que fundamentam as referidas discussões, de maneira a problematizá-las, tendo em vista a noção de justiça distributiva.(AU)


This study discusses the ontological assumptions assumed in the bioethical debate about human genetic selection and gene editing. With a view to managing genetic disorders, different therapies have been employed clinically and experimentally, since the 1990s. Among the treatment strategies, we find embryo selection (by means of pre-implantation genetic diagnosis) and gene therapy (by means of gene editing). The development of these techniques raises discussions about their ethical implications. This article postulates that different conceptions of humanity can be identified in these discussions, grounding ethical positions regarding genome interventions. The article seeks to analyze these conceptions, following three steps. First, the biomedical context of genetic selection and gene editing is presented. Then, discussions on the ethical aspects of these interventions are highlighted. Finally, different conceptions of humanity grounding these discussions are identified and analyzed, considering the notion of distributive justice.(AU)


Subject(s)
Humans , Selection, Genetic , Genome, Human , Bioethical Issues
12.
Gac. méd. Méx ; 156(1): 53-59, ene.-feb. 2020.
Article in Spanish | LILACS | ID: biblio-1249870

ABSTRACT

Resumen En este ensayo se analizan las implicaciones bioéticas de la reciente manipulación genética en embriones humanos con CRISPR-Cas9 para eliminar el gen CCR5 y el nacimiento de dos gemelas discordantes. El experimento se divulgó en medios sociales. Los principales problemas bioéticos identificados son la justificación del modelo, el proceso de consentimiento informado y la falta de declaración de evidentes conflictos de interés. No se evaluaron apropiadamente las consecuencias del experimento sobre la vida de las gemelas nacidas como la afectación a su autonomía, los supuestos beneficios por recibir y los riesgos futuros de daño durante su vida. Habiendo manipulado la línea celular germinal, no se consideraron los efectos sobre su descendencia futura. Este tipo de acciones tiene un impacto negativo en la forma como la sociedad concibe la ciencia. La ingeniería genética debe reservarse al contexto experimental básico o bien como investigación cínica para la corrección de enfermedades conocidas graves de origen genético, bajo estricta supervisión regulatoria y bioética y de manera gradualista de acuerdo con el progreso de las técnicas de edición genética.


Abstract In this essay, the bioethical implications of the recent genetic manipulation in human embryos with CRISPR-Cas9 to eliminate the CCR5 gene and the birth of a pair of discordant twin girls are analyzed. The experiment was disseminated via social media. The main bioethical flaws identified include the justification of the model, the informed consent process and the lack of disclosure of evident conflicts of interest. The consequences of the experiment on the life of the twins that were born were not properly evaluated, such as the impact on their autonomy, the alleged benefits to be received and the future risks of harm during their lifetime. Having manipulated the germ cell line, the effects on their future offspring were not considered. This type of actions negatively affects the way society conceives science. Genetic engineering should be reserved to the basic experimental context or as clinical research for the correction of known serious diseases of genetic origin under strict regulatory and bioethical supervision and using a gradualist approach in accordance with the advances of gene editing techniques.


Subject(s)
Humans , Female , Receptors, CCR5/genetics , CRISPR-Cas Systems , Gene Editing/ethics , Publishing/ethics , Research Design , Twins, Dizygotic , Genetic Engineering/classification , Genetic Engineering/ethics , Genome, Human , HIV Infections/prevention & control , China , Conflict of Interest , Sperm Injections, Intracytoplasmic , Bioethical Issues , Therapeutic Human Experimentation/ethics , Informed Consent/ethics
13.
Journal of Experimental Hematology ; (6): 942-947, 2020.
Article in Chinese | WPRIM | ID: wpr-827181

ABSTRACT

OBJECTIVE@#To analyze the genome-wide DNA methylation differences in umbilical cord blood nucleated red blood cells (NRBCs) between term and preterm infants by using the methylation gene chip technology, and to screen the genes of differential methylation and biological signaling pathways which may be related to the expression of γ-globin gene (HBG).@*METHODS@#Umbilical cord bloods of eight term infants and eight preterm infants were collected, and NRBCs of each sample was isolated, then genome DNA was extracted and bisulfite conversion was performed. The DNA methylation sites were detected by using the Illumina 850K BeadChip. Differential DNA methylation sites were screened, and the function of genes with differential methylation was analyzed by using GO and KEGG enrichment analysis.@*RESULTS@#Compared with the preterm group, 4749 differential DNA methylation sites of term group were screened out, including 4359 hypomethylation sites and 390 hypermethylation sites. GO and KEGG analysis indicated that the function of genes with differential methylation mainly involved in the hemopoietic system, growth and development process, Wnt and Notch signal pathways.@*CONCLUSION@#The differentical methylation sites at genome-wide level in umbilicar cord blood NRBC of term and preterm infants have been obtained, and the signal pathway and genes which possibily related with swiching the expression of γ-globin gene to β-globin gene have been screened-out. This study provide the new targets for studing the mechamism regulating expression of HBG gene.


Subject(s)
Humans , Infant, Newborn , DNA , DNA Methylation , Epigenesis, Genetic , Fetal Blood , Genome, Human , Infant, Premature
14.
Rev. Investig. Salud. Univ. Boyacá (En línea) ; 7(2): 138-172, 2020. tab, ilust
Article in Spanish | LILACS, COLNAL | ID: biblio-1292512

ABSTRACT

Introducción: el objetivo de la secuenciación es determinar la composición de los nucleótidos presentes en el ADN o el ARN. Desde la finalización del proyecto genoma humano, surgieron diversas tecnologías de secuenciación rápida como Roche 454, SOLiD, Illumina, Ion Torrent, PacBio y Oxford Nanopore, más precisas y costoeficientes, que permiten desarrollar proyectos a gran escala y estudiar genes y genomas, la composición de microbiomas, enfermedades metabólicas y enfermedades genéticas que afectan a la población. Objetivo: describir los fundamentos de los métodos de secuenciación de ADN y sus aplicaciones en las ciencias biomédicas. Métodos: revisión descriptiva de las principales estrategias de secuenciación de ADN de primera, segunda y tercera generación y su aplicación en el entorno biomédico, a partir de la búsqueda de artículos en bases de datos electró-nicas especializadas en investigación científica. Se encontraron 118 documentos, de los cuales se excluyeron 6, por no cumplir con los criterios de inclusión, y se seleccionaron 112, por cumplir con todos los requisitos. Conclusiones:el surgimiento de los métodos de secuenciación de siguiente generación arroja una gran canti-dad de datos, incluidos genomas secuenciados completamente de varias especies, con un rendimiento extenso, tiempos reducidos y costoeficiencia, que lleva a la completa transformación de las ciencias de la vida y logra un progreso sin precedentes en el análisis de genomas, la evaluación de la ecología microbiana y el diagnóstico de enfermedades.


Introduction: The purpose of sequencing is to determine the composition of the nucleotides present in DNA or RNA. Since the completion of the human genome project, several sequencing technologies such as Roche 454, SOLiD, Illumina, Ion Torrent, PacBio and Oxford Nanopore have emerged as tools for rapid sequencing, with greater precision and cost-efficiency, allowing the development of lar-ge-scale projects and the study of genes and genomes, along with the composition of microbiomes and the study of metabolic and genetic diseases that affect the population. Objective: To describe the foundations of the methods of DNA sequencing and their applications in the biomedical sciences. Methods: Descriptive review of the main strategies of first, second and third generation DNA sequencing and their application in the biomedical environment. This review was carried out by searching articles in electronic databases specialized in scientific research. A total of 118 papers were found, of which 6 were excluded as they did not meet the inclusion criteria and 112 were selected as meeting all the requirements. Conclusions: The emergence of next-generation sequencing methods yielding a wealth of data, including fully sequenced genomes of various species, with extensive throughput, reduced time and cost-effec-tiveness that has led to the complete transformation of the life sciences, achieving unprecedented progress in genome analysis, assessment of microbial ecology and disease diagnosis


Introdução: o objetivo do sequenciamento é determinar a composição dos nucleotídeos presentes no DNA ou RNA. Desde a conclusão do projeto do genoma humano, surgiram diversas tecnologias de sequenciamento rápida como Roche 454, SOLiD, Illumina, Ion Torrent, PacBio e Oxford Nanopore, mais precisas e econômicas, que permitem o desenvolvimento de projetos de grande escala e estudo de genes e genomas, composição de microbiomas, doenças metabólicas e genéticas que afetam a popula-ção. Objetivo: descrever os fundamentos dos métodos de sequenciamento de DNA e suas aplicações nas ciências biomédicas. Métodos: revisão descritiva das principais estratégias de sequenciamento de DNA de primeira, segunda e terceira geração e sua aplicação no ambiente biomédico, a partir da busca de artigos em bases de dados eletrônicas especializadas em pesquisa científica. Foram encontrados 118 documen-tos, dos quais 6 foram excluídos por não atenderem aos critérios de inclusão e 112 fo-ram seleciona-dos por atenderem a todos os requerimentos. Conclusões: o surgimento de métodos de sequenciamento de próxima geração rende uma riqueza de dados, incluindo genomas totalmente se-quenciados de várias espécies, com produção extensa, tempos reduzidos e eficiência de custo, levando à transformação completa das ciências da vida e alcançando um progresso sem precedentes no genoma análise, avaliação de ecologia microbiana e diagnóstico de doenças.


Subject(s)
High-Throughput Nucleotide Sequencing , DNA , Genome, Human , Genetic Techniques , Sequence Analysis
15.
Rev. MED ; 27(2): 7-9, jul.-dic. 2019.
Article in Spanish | LILACS | ID: biblio-1115224
17.
Gac. méd. Méx ; 155(5): 463-470, Sep.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1286544

ABSTRACT

The first draft of the human genome sequencing published in 2001 reported a large number of single nucleotide polymorphisms (SNPs). Given that these polymorphisms could practically represent all the variability involved in the susceptibility, protection, severity, among other aspects, of various common diseases, as well as in their response to medications, it was thought that they might be “the biomarkers of choice” in personalized genomic medicine. With the new information obtained from the sequencing of a larger number of genomes, we have understood that SNPs are only an important part of the genetic markers involved in these traits. In addition to SNPs, other variants have been identified, such as insertions/deletions (INDELs) and copy number variants (CNVs), which – in addition to classic variable number tandem repeats (VNTRs) and short tandem repeats (STRs) – originate or contribute to the development of diseases. The use of these markers has served to identify regions of the genome involved in Mendelian diseases (one gene-one disease) or genes directly associated with multifactorial diseases. This review has the purpose to describe the role of STRs, VNTRs, SNPs, CNVs and INDELs in linkage and association studies and their role in Mendelian and multifactorial diseases.


Subject(s)
Humans , Genetic Variation/physiology , Disease/genetics , Polymorphism, Single Nucleotide , Genetic Markers , Genome, Human , Mutagenesis, Insertional , Gene Deletion , Tandem Repeat Sequences , Lod Score , Mutation
19.
Genomics, Proteomics & Bioinformatics ; (4): 211-218, 2019.
Article in English | WPRIM | ID: wpr-772957

ABSTRACT

As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits, a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data, sample quality issues, such as gender mismatch, abnormal inbreeding coefficient, cryptic relatedness, and population outliers, can also have fundamental impact on downstream analysis. However, there is a lack of tools specialized in identifying problematic samples from NGS data, often due to the limitation of sample size and variant counts. We developed SeqSQC, a Bioconductor package, to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access, and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at http://bioconductor.org/packages/SeqSQC.


Subject(s)
Female , Humans , Breast Neoplasms , Genetics , Cohort Studies , Racial Groups , Genetics , Genome, Human , High-Throughput Nucleotide Sequencing , Methods , Reference Standards , Software , Exome Sequencing
20.
Chinese Journal of Biotechnology ; (12): 1295-1306, 2019.
Article in Chinese | WPRIM | ID: wpr-771799

ABSTRACT

Tumor-specific gene mutations might generate suitable neoepitopes for cancer immunotherapy that are highly immunogenic and absent in normal tissues. The high heterogeneity of the tumor genome poses a big challenge for precision cancer immunotherapy. Mutations characteristic of each tumor can help to distinguish it from other tumors. Based on these mutations' characteristic, it is possible to develop immunotherapeutic strategies for specific tumors. In this study, a tumor neoantigen prediction scheme was proposed, in which both the intracellular antigen presentation process and the ability to bind with extracellular MHC molecule were taken into consideration. The overall design is meritorious and may help reduce the cost for validation experiments compared with conventional methods. This strategy was tested with several cancer genome datasets in the TCGA database, and a number of potential tumor neoantigens were predicted for each dataset. These predicted neoantigens showed tumor type specificity and were found in 20% to 70% of cancer patients. This scheme might prove useful clinically in future.


Subject(s)
Humans , Antigens, Neoplasm , Computational Biology , Genome, Human , Immunotherapy , Mutation , Neoplasms
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