Análisis de la variabilidad genética de una muestra de la población de Bogotá: hacia la constitución de un mapa de haplotipos / Genetic variability analysis in a population from Bogotá: Towards a haplotype map

Resumen Introducción. Los proyectos del mapa de haplotipos (HapMap) y de los 1.000 genomas han sido fundamentales para la compresión del componente genético de las enfermedades comunes y los fenotipos normales. Sin embargo, la variabilidad genética colombiana incluida en estos proyectos no es representativa del país. Objetivo. Contribuir al conocimiento de la variabilidad genética de la población colombiana a partir del estudio genómico de una muestra de individuos de Bogotá. Materiales y métodos. Se genotipificaron 2'372.784 marcadores genéticos de 32 individuos nacidos en Bogotá y de padres originarios de la misma ciudad utilizando la plataforma Illumina™. Los niveles de variabilidad genética se determinaron y se compararon con los datos disponibles de otras poblaciones del proyecto de los 1.000 genomas. Resultados. Los individuos analizados presentaron una variabilidad genética semejante a la de poblaciones con las que comparten ancestros. No obstante, a pesar de la poca diferenciación genética detectada en la población de Bogotá y en la de Medellín, el análisis de los componentes principales sugiere una composición genética diferente en las dos poblaciones. Conclusiones. El análisis genómico de la muestra de Bogotá permitió detectar similitudes y diferencias con otras poblaciones americanas. El aumento de tamaño de la muestra bogotana y la inclusión de muestras de otras regiones del país permitirán una mejor compresión de la variabilidad genética en Colombia, lo cual es fundamental para los estudios de salud humana, y la prevención y el tratamiento de enfermedades comunes en el país.

Abstract Introduction: The HapMap and the 1000 Genomes projects have been important for understanding the genetic component of common diseases and normal phenotypes. However, the Colombian genetic variability included in these projects is not fully representative of our country. Objective: To contribute to the knowledge of the Colombian genetic variability through the genomic study of a sample of individuals from Bogotá. Materials and methods: A total of 2,372,784 genetic markers were genotyped in 32 individuals born in Bogotá whose parents are from the same region, using the Illumina™ platform. The genetic variability levels were determined and compared with the data available from other populations of the 1000 Genomes Project. Results: The genetic variability detected in the individuals from Bogotá was similar to those with shared ancestry. However, despite the low levels of genetic differentiation between Bogotá and Medellín, populations the principal component analysis suggested a different genetic composition in them. Conclusions: Our genomic analysis of a Bogotá sample allowed us to detect similarities and differences with other American populations. The increase of the Bogotá sample and the inclusion of samples from other regions of the country will improve our understanding of the genetic variability in Colombia, essential for studies of human health and the prevention and treatment of common diseases in our country.

Direitos fundamentais, democracia e o Projeto Genoma Humano: bioética e biopolítica / Fundamental rights, democracy and the Human Genome Project: bioethical and biopolitics / Derechos fundamentales, democracia y el Proyecto Genoma Humano: bioética y biopolítica

Resumo Além de importante tecnologia da atualidade, o Projeto Genoma Humano é estrutura política e econômica de produção e reprodução de conceito dominante de saúde. Nessa perspectiva, esta pesquisa discute a garantia da autonomia e liberdade de escolha dos padrões físico-biológicos das atuais e futuras gerações em sociedade na qual esses padrões são historicamente reproduzidos por relações de poder. Para tanto, analisa-se o Projeto Genoma Humano considerando a tensão entre constitucionalismo e democracia, de modo a aproximar aportes da bioética, do biodireito e da biopolítica a partir de perspectiva crítica da sociedade. Como resultado, propõe-se, para reflexão, a institucionalização de audiências públicas baseadas no modelo de democracia deliberativa.

Abstract The Human Genome Project constitutes an important contemporary health technology, but it is also a political and economical structure which of production and reproduction of a dominant concept of health. In this perspective, this research aims to discuss the question of the guarantee of autonomy and freedom of choice of the physical-biological patterns of the future generations, in a society in which those patterns are historically reproduced by power relations. For this reason, a methodology of analysis of the Human Genome Project is used in the context of the tension between constitutionalism and democracy, in order to establish an approximation between the contributions of Bioethics, Biolaw and Biopolitics, in the context of a critical perspective of our society. As a result we propose a reflection about the institutionalisation of public hearings articulated from a model of deliberative democracy.

Resumen El Proyecto Genoma Humano constituye una importante tecnología de salud de la contemporaneidad, pero también una estructura política y económica de producción y reproducción de un concepto dominante de salud. En esa perspectiva, esta investigación tiene como objetivo discutir la cuestión de la garantía de la autonomía y de la libertad de elección de los patrones físicos y biológicos de las futuras generaciones, en una sociedad en la cual estos patrones son históricamente reproducidos por relaciones de poder. Para ello, se utiliza una metodología de análisis del PGH en el ámbito de la tensión entre constitucionalismo y democracia, de modo tal de establecer una aproximación entre los aportes de la Bioética, el Bioderecho y la Biopolítica, en el contexto de una perspectiva crítica de la sociedad. Como resultado, se propone para la reflexión la institucionalización de audiencias públicas articuladas a partir de un modelo de democracia deliberativa.

National human genome projects: an update and an agenda / 한국역학회지

Population genetic and human genetic studies are being accelerated with genome technology and data sharing. Accordingly, in the past 10 years, several countries have initiated genetic research using genome technology and identified the genetic architecture of the ethnic groups living in the corresponding country or suggested the genetic foundation of a social phenomenon. Genetic research has been conducted from epidemiological studies that previously described the health or disease conditions in defined population. This perspective summarizes national genome projects conducted in the past 10 years and introduces case studies to utilize genomic data in genetic research.

National human genome projects: an update and an agenda / 한국역학회지

Population genetic and human genetic studies are being accelerated with genome technology and data sharing. Accordingly, in the past 10 years, several countries have initiated genetic research using genome technology and identified the genetic architecture of the ethnic groups living in the corresponding country or suggested the genetic foundation of a social phenomenon. Genetic research has been conducted from epidemiological studies that previously described the health or disease conditions in defined population. This perspective summarizes national genome projects conducted in the past 10 years and introduces case studies to utilize genomic data in genetic research.

Trends in Next-Generation Sequencing and a New Era for Whole Genome Sequencing / 대한배뇨장애요실금학회지

This article is a mini-review that provides a general overview for next-generation sequencing (NGS) and introduces one of the most popular NGS applications, whole genome sequencing (WGS), developed from the expansion of human genomics. NGS technology has brought massively high throughput sequencing data to bear on research questions, enabling a new era of genomic research. Development of bioinformatic software for NGS has provided more opportunities for researchers to use various applications in genomic fields. De novo genome assembly and large scale DNA resequencing to understand genomic variations are popular genomic research tools for processing a tremendous amount of data at low cost. Studies on transcriptomes are now available, from previous-hybridization based microarray methods. Epigenetic studies are also available with NGS applications such as whole genome methylation sequencing and chromatin immunoprecipitation followed by sequencing. Human genetics has faced a new paradigm of research and medical genomics by sequencing technologies since the Human Genome Project. The trend of NGS technologies in human genomics has brought a new era of WGS by enabling the building of human genomes databases and providing appropriate human reference genomes, which is a necessary component of personalized medicine and precision medicine.

Las neuronas de Dios: Una neurociencia de la religión, la espiritualidad y la luz al final del tunel / God's Neurons: A Neuroscience of Religion, Spirituality, and Light at the End of the Tunnel

Por primera vez, las ciencias naturales pueden estudiar la religión en lugar de burlarse de ella; por primera vez, la ciencia puede responder una pregunta inquietante: ¿por qué, en pleno siglo XXI, seguimos creyendo en algo o alguien superior, llámese Dios, meditación trascendental, espiritualidad o sentido de la vida? ¿De dónde surge esta necesidad, antigua como nuestra especie, que en algún momento de nuestras vidas nos lleva a preguntarnos por lo que habrá "después" o lo que está "más allá"? ¿Viene "de fábrica" o es un producto de la cultura?. En su viaje al corazón de las creencias, el autor pasa revista a un sinfín de experimentos que muestran cómo actúan las neuronas de monjas rezadoras, budistas meditadores, pentecostales o iluminados con LSD, peyote, ayahuasca y hongos alucinógenos varios. Sin olvidar a las personas que han atravesado experiencias límite, como trances epilépticos o la vivencia de la propia muerte con la misteriosa luz al final del túnel. Los resultados permiten identificar circuitos neuronales que están en la base de visiones y experiencias místicas. Y hay más: los estudios revelan también que la religión tiene un efecto ansiolítico, estimula la empatía con los demás y los lazos comunitarios, y aporta mayor seguridad personal

El cáncer de mama en la era posgenómica. La importancia del proyecto Atlas del Genoma del Cáncer (TCGA) y de los biobancos de investigación en cáncer de mama / Breast cancer in the post-genomic era. The importance of the Atlas Cancer Genome Project ( TCGA ) and biobank research in breast cancer

Personalizada, Predictiva y Preventiva. En una medicina de la era posgenómica que vira hacia el paradigma de las 3P, los biobancos emergen como una necesidad de muestras de muy alta calidad para las nuevas tecnologías de secuenciación genética de última generación a gran escala, como los next generation sequencers.

Next-Generation Sequencing and Epigenomics Research: A Hammer in Search of Nails

After the initial enthusiasm of the human genome project, it became clear that without additional data pertaining to the epigenome, i.e., how the genome is marked at specific developmental periods, in different tissues, as well as across individuals and species-the promise of the genome sequencing project in understanding biology cannot be fulfilled. This realization prompted several large-scale efforts to map the epigenome, most notably the Encyclopedia of DNA Elements (ENCODE) project. While there is essentially a single genome in an individual, there are hundreds of epigenomes, corresponding to various types of epigenomic marks at different developmental times and in multiple tissue types. Unprecedented advances in next-generation sequencing (NGS) technologies, by virtue of low cost and high speeds that continue to improve at a rate beyond what is anticipated by Moore's law for computer hardware technologies, have revolutionized molecular biology and genetics research, and have in turn prompted innovative ways to reduce the problem of measuring cellular events involving DNA or RNA into a sequencing problem. In this article, we provide a brief overview of the epigenome, the various types of epigenomic data afforded by NGS, and some of the novel discoveries yielded by the epigenomics projects. We also provide ample references for the reader to get in-depth information on these topics.

The Impact of Transposable Elements in Genome Evolution and Genetic Instability and Their Implications in Various Diseases

Approximately 45% of the human genome is comprised of transposable elements (TEs). Results from the Human Genome Project have emphasized the biological importance of TEs. Many studies have revealed that TEs are not simply "junk" DNA, but rather, they play various roles in processes, including genome evolution, gene expression regulation, genetic instability, and cancer disposition. The effects of TE insertion in the genome varies from negligible to disease conditions. For the past two decades, many studies have shown that TEs are the causative factors of various genetic disorders and cancer. TEs are a subject of interest worldwide, not only in terms of their clinical aspects but also in basic research, such as evolutionary tracking. Although active TEs contribute to genetic instability and disease states, non-long terminal repeat transposons are well studied, and their roles in these processes have been confirmed. In this review, we will give an overview of the importance of TEs in studying genome evolution and genetic instability, and we suggest that further in-depth studies on the mechanisms related to these phenomena will be useful for both evolutionary tracking and clinical diagnostics.

Next Generation DNA Sequencing and Its Application in Clinical Medicine / 대한주산의학회잡지

Watson and Crick published a paper on the double helical structure of DNA in Nature in April 25, 1953. The human genome is contained in the 23 pairs of chromosomes and in the mitochondrial DNA of each cell. The Human Genome Project was launched in 1990 under the direction of Watson and concluded in 2003, on the 50th anniversary of Watson and Crick paper. Over 6 billion of nucleotides of genetic codes are in single cells. There are 23,000 protein coding genes and the remainder are non-coding DNA, regulatory DNA. Since the completion of Human Genome Project, these huge genomic information has been translated into clinically usable medical information. With the advent of massively parallel DNA sequencing, known as next generation DNA sequencing, the cost and turn-around time were significantly reduced so that the era of Whole Genome Sequencing entered into hospitals and medical clinics. On June 16, 2014 American Society of Human Genetics revised its mission statement as follows. "Our mission is to advance human genetics in science, health and society through research, education and advocacy". Finally medical genetics nestled its roots in the midst of genetics and genomics.

A bioinformática na pesquisa odontológica brasileira / The bioinformatics in the Brazilian oral research / La bioinformática en la investigación odontológica brasileña

Objetivo: Avaliar o papel da bioinformática na pesquisa odontológica brasileira. Métodos: Foram analisados os resumos das reuniões da Sociedade Brasileira de Pesquisa Odontológica (SBPqO), de 2005 a 2011. As palavras-chave bioinformática, genbank, seqüenciamento/seqüenciada(o), PCR em tempo real, microarranjo e projeto genoma foram pesquisadas em português e inglês. Os dados foram tabulados de acordo com a instituição pesquisadora (publica ou privada e sua localização no país) e com a categoria de apresentação (estudante de graduação ou profissional graduado). Resultado: Verificou-se que o número de resumos com as palavras-chave aumentou de 2005 para 2011; entretanto, a maioria foi realizada por instituições públicas, no sudeste do Brasil e por graduados. Conclusão: A quantidade de pesquisas odontológicas usando bioinformática está crescendo, porém, ainda será necessário que esta tecnologia alcance todas as regiões do país e todos os níveis de estudantes, integrando também os graduandos com as ferramentas de bioinformática.

Objective: To verify the role of bioinformatics in the Brazilian oral research. Methods: The abstracts of Brazilian Oral Research Society (SBPqO) meetings were investigated, from 2005 to 2011. The key-words:bioinformatics, genbank, sequencing/sequence, real time PCR, microarray and genome project were searched in English and Portuguese languages. The data were tabulated according to the research institution(private or public and country location) and to the category of the speaker (graduating student or professional). Results: It could be seen that the number of abstracts with the key-words increased from 2005 to 2011; however, the majority was performed in public institutions, in Brazilian southeast and by graduated speakers. Conclusion: The amount of Brazilian oral researches using bioinformatics is increasing; however, it is necessary that this technology reach all the regions of the country and also all the degrees of students, integrating the graduate learners to bioinformatics tools.

Objetivo: Evaluar el papel de la bioinformática en la investigación odontológica brasileña. Métodos: Analizaron los resúmenes de las reuniones de la Sociedad Brasileña para la Investigación Odontológica (SBPqO), de 2005 a 2011. Los descriptores: bioinformática, GenBank, secuencia / secuenciada (o), PCR en tiempo real, microarray y proyecto genoma fueron buscados en Inglés y Portugués. Los datos fueron tabulados de acuerdo con la institución de investigación (públicos o privados y su ubicación en el país) y la categoría de presentación (estudiante graduado o título profesional). Resultados: Se encontró que el número de resúmenes con palabras clave se incrementó de 2005 a 2011, sin embargo, la mayoría estaba en manos de las instituciones públicas, en el sureste de Brasil y graduados. Conclusión: La cantidad de investigación odontológica utilizando la bioinformática está creciendo, todavía necesitan esta tecnología llegue a todos las regiones del país y todos los niveles de estudiantes, graduados también la integración con las herramientas de la bioinformática.

ENCODE: A Sourcebook of Epigenomes and Chromatin Language

Until recently, since the Human Genome Project, the general view has been that the majority of the human genome is composed of junk DNA and has little or no selective advantage to the organism. Now we know that this conclusion is an oversimplification. In April 2003, the National Human Genome Research Institute (NHGRI) launched an international research consortium called Encyclopedia of DNA Elements (ENCODE) to uncover non-coding functional elements in the human genome. The result of this project has identified a set of new DNA regulatory elements, based on novel relationships among chromatin accessibility, histone modifications, nucleosome positioning, DNA methylation, transcription, and the occupancy of sequence-specific factors. The project gives us new insights into the organization and regulation of the human genome and epigenome. Here, we sought to summarize particular aspects of the ENCODE project and highlight the features and data that have recently been released. At the end of this review, we have summarized a case study we conducted using the ENCODE epigenome data.

Current Status and Future Promise of the Human Microbiome / 대한소아소화기영양학회지

The human-associated microbiota is diverse, varies between individuals and body sites, and is important in human health. Microbes in human body play an essential role in immunity, health, and disease. The human microbiome has been studies using the advances of next-generation sequencing and its metagenomic applications. This has allowed investigation of the microbial composition in the human body, and identification of the functional genes expressed by this microbial community. The gut microbes have been found to be the most diverse and constitute the densest cell number in the human microbiota; thus, it has been studied more than other sites. Early results have indicated that the imbalances in gut microbiota are related to numerous disorders, such as inflammatory bowel disease, colorectal cancer, diabetes, and atopy. Clinical therapy involving modulating of the microbiota, such as fecal transplantation, has been applied, and its effects investigated in some diseases. Human microbiome studies form part of human genome projects, and understanding gleaned from studies increase the possibility of various applications including personalized medicine.

Perspectives on Clinical Informatics: Integrating Large-Scale Clinical, Genomic, and Health Information for Clinical Care

The advances in electronic medical records (EMRs) and bioinformatics (BI) represent two significant trends in healthcare. The widespread adoption of EMR systems and the completion of the Human Genome Project developed the technologies for data acquisition, analysis, and visualization in two different domains. The massive amount of data from both clinical and biology domains is expected to provide personalized, preventive, and predictive healthcare services in the near future. The integrated use of EMR and BI data needs to consider four key informatics areas: data modeling, analytics, standardization, and privacy. Bioclinical data warehouses integrating heterogeneous patient-related clinical or omics data should be considered. The representative standardization effort by the Clinical Bioinformatics Ontology (CBO) aims to provide uniquely identified concepts to include molecular pathology terminologies. Since individual genome data are easily used to predict current and future health status, different safeguards to ensure confidentiality should be considered. In this paper, we focused on the informatics aspects of integrating the EMR community and BI community by identifying opportunities, challenges, and approaches to provide the best possible care service for our patients and the population.

A Short History of the Genome-Wide Association Study: Where We Were and Where We Are Going

Recent rapid advances in genetic research are ushering us into the genome sequence era, where an individual's genome information is utilized for clinical practice. The most spectacular results of the human genome study have been provided by genome-wide association studies (GWASs). This is a review of the history of GWASs as related to my work. Further efforts are necessary to make full use of its potential power to medicine.

Medicina genómica: [editorial] / Genomic Medicine: [editorial]

Until the twilight of the 20th century, genetics was a branch of medicine applied to diseases of rare occurrence. The advent of the human genome sequence and the possibility of studying it at affordable costs for patients and healthcare institutions, has permitted its application in high-priority diseases like cancer, cardiovascular disease, diabetes, and Alzheimer’s, among others.There is great potential in predictive and preventive medicine, through studying polymorphic genetic variants associated to risks for different diseases. Currently, clinical laboratories offer studies of over 30,000 variants associated with susceptibilities, to which individuals can access without much difficulty because a medical prescription is not required. These exams permit conducting a specific plan of preventive medicine. For example, upon the possibility of finding a deleterious mutation in the BRCA1 and BRCA2 genes, the patient can prevent the breast cancer by mastectomy or chemoprophylaxis and in the presence of polymorphisms associated to cardiovascular risk preventive action may be undertaken through changes in life style (diet, exercise, etc.)...

Hasta finales del siglo XX la genética era una rama de la medicina que se aplicaba a enfermedades de ocurrencia rara. El advenimiento de la secuencia del genoma humano y la posibilidad de estudiarlo a un costo asequible para pacientes y entidades prestadoras de salud, ha permitido su aplicación en enfermedades de alta prioridad como el cáncer, las enfermedades cardiovasculares, la diabetes y el Alzheimer, entre otras.Hay grandes potenciales en la medicina predictiva y preventiva, mediante el estudio de variantes genéticas polimórficas asociadas con riesgos para diferentes enfermedades. En la actualidad hay laboratorios clínicos que ofrecen el estudio de más de 30,000 variantes asociadas con susceptibilidades, a los que los individuos pueden acceder sin mayores dificultades porque no es necesaria una orden médica. Estos exámenes permiten realizar un plan específico de medicina preventiva. Por ejemplo, ante la posibilidad de encontrar una mutación deletérea en los genes BRCA1 y BRCA2, la paciente puede prevenir el cáncer de mama mediante la mastectomía o la quimioprofilaxis y ante la presencia de polimorfismos asociados con riesgo cardiovascular puede realizar prevención mediante el cambio en el estilo de vida (dieta, ejercicio, etc.)...

Medicina genômica personalizada aqui e agora / Personal genomic medicine here and now

A Medicina Genômica é uma revolução em curso, baseada em testes genéticos que permitem o conhecimento do mapa de predisposições genéticas de cada indivíduo. O uso de técnicas de altíssima eficiência permite estudar simultaneamente variações individuais em centenas de milhares de genes, a custo cada dia mais baixo. O resultado dos testes possibilita praticar o que antes era impossível: uma medicina verdadeiramente personalizada, preditiva, pró-ativa, preventiva e participativa. Conhecendo a intimidade das variações genômicas que determinam predisposições e resistências de cada pessoa, é possível manipular o ambiente (estilo de vida, dieta, adição ou remoção de fármacos, cirurgias preventivas) de forma a manter o equilíbrio harmônico genoma/ ambiente que caracteriza a saúde. A partir do teste monitor genômico, e acesso à Medicina Genômica personalizada já é possível aqui e agora.

Genomic Medicine is a revolution in progress, based on genetic tests that allow the knowledge of each individual's map of genetic predispositions. Using high efficiency techniques allows the study of individual variations simultaneouslv in hundreds of thousands of genes, each day at a lower cost. The tests results make possible what was once impossible: to practice the actually personalized medicine, predictive, pro-active, preventive and participative. Knowing the privacy of genomic variations that determine biases and strengths of each person, you can manipulate the environment (lifestyle, diet, addition or removal of drugs, preventive surgeries) in order to maintain the harmonious balance genome / environment that characterizes the health. From the genomic test monitor, the access to personalized genomic medicine is already possible here and now.

From human genome to man-made life: J. Craig Venter leads the life sciences / 生物工程学报

For the first time ever, the scientists of J. Craig Venter team have created actual self-replicating synthetic life. The research was just published in the Journal of Science on May 20, 2010. Although this news immediately brings the worry about the possible potential threat to biosecurity and biosafety as well as the ethical disputes, it yet indicates that mankind have made a new step forward in synthetic biology. In the time of post-genome era, we believe the advancement of synthetic biology that might affect or change the future life of human being will be widely used in energy, environment, materials, medication and many other fields.