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Este artículo revisa los principales desafíos éticos que plantea la investigación vinculada al genoma humano a la luz de la bibliografía internacional y entrega recomendaciones sobre su abordaje basada en nuestra experiencia en el Comité de Ética para la Investigación en Seres Humanos de la Facultad de Medicina, Universidad de Chile, incluyendo las regulaciones legales nacionales. Los estándares éticos de la investigación en seres humanos deben extremarse para proteger adecuadamente a los participantes en estudios involucrados con la genómica. Especialmente relevantes en este contexto son: la protección de la confidencialidad y anonimato; la política de entrega de resultados y la posibilidad de retirarse del estudio. Compartir datos resultantes de investigaciones genéticas permite optimizar recursos, otorga mayor transparencia y replicabilidad de los análisis y permite descubrir alteraciones genéticas responsables de enfermedades raras y genes involucrados en enfermedades hereditarias multifactoriales, además de contribuir al diseño de medicina de precisión y de nuevas estrategias terapéuticas. Sin embargo, plantea grandes desafíos: proteger la privacidad y evitar la re-identificación de los voluntarios, la entrega de resultados con asesoría pre y post estudio. Estos aspectos requieren la elaboración de un cuidadoso proceso de consentimiento informado para investigaciones genómicas cuyos componentes principales se analizan en este artículo.

This article reviews the main ethical challenges posed by human genome research in the light of the international literature and provides recommendations on how to approach them based on our experience in the Ethics Committee for Research on Human Subjects of the Faculty of Medicine, University of Chile, including national legal regulations. Ethical standards in human research must be extreme, in order to adequately protect participants in studies involving genomics. Particularly relevant in this context are the protection of confidentiality and anonymity; the policy of delivery of results and the possibility of withdrawing from the study. Sharing data resulting from genetic research optimizes resources, provides greater transparency, and replicability of the analyses and makes it possible to discover genetic alterations responsible for rare diseases and genes involved in multi-factorial hereditary diseases, as well as contributing to the design of precision medicine and new therapeutic strategies. However, it poses great challenges: protecting privacy and avoiding re-identification of volunteers, delivery of results with pre- and post-study counseling. These aspects require the elaboration of a careful informed consent process for genomic research, the main components of which are discussed in this article.

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46,XX testicular disorder of sex development is a rare syndrome characterized by an inconsistency between genotype and phenotype. Affected individuals present variant genitalia between male and ambiguous, non-functional testicles, non-obstructive azoospermia, generally accompanied by hypergonadotropic hypogonadism, a condition known for high levels of gonadotrophic hormones. In some cases, disorders of sexual development are diagnosed during puberty. However, a significant number of individuals show physical characteristics common to males that are not clinically suspicious. As a result, patients with the condition may remain undiagnosed. Many individuals with the condition are diagnosed as adults, due to infertility. The present study discusses the case of an individual who underwent karyotyping for sterility and was found to be a 46,XX male. Despite having a female karyotype, the presence of the sex-determining region Y gene explains the manifestation of masculine secondary sex characteristics. This report highlights the importance of genetic evaluation, considering that carriers may present significant complications resulting from the disorder. Based on correct diagnosis, it is possible to improve a carrier's quality of life through multidisciplinary approaches and help them achieve pregnancy through assisted reproductive technology treatments.

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ABSTRACT Objective: A scientometric analysis produced in ophthalmic genetics and gene therapy research is lacking. The purpose of this study is to present a holistic analysis of ophthalmic genetics literature. Methods: The data used in this study were obtained from the Web of Science (WoS) Core Collection. All published documents between 1975-2019 were included. The data exported from WoS enabled the extensive details of ophthalmic genetics related literature including countries, institutions, authors, citations and keywords. Scientometric network maps of keywords and also country and institution co-authorships were created with free software. Global contributions of the countries to the ophthalmic genetics literature were shown by a graphic. Results: The search query revealed a total of 2322 documents. Most of the documents were original articles (75.75%). USA was the leading country by producing 45.39% of all documents in ophthalmic genetics research followed by UK, Germany, China and France. Pennsylvania University was the most contributing institution in the literature (5.25%) followed by University College London and Moorfields Eye Hospital. The average citations per item was 29.4. The most used keywords over a 40-year period were 'family', 'cell', 'photoreceptor' and 'expression'. Conclusions: USA and UK dominated the ophthalmic genetics research. A substantial increase in the number of published documents in this field were observed after 2010.

RESUMO Objetivo: A literatura carece de análise cienciométrica produzida em genética oftálmica e de pesquisa em terapia genética. O objetivo deste estudo é apresentar uma análise holística da literatura genética oftálmica. Métodos: Os dados utilizados neste estudo foram obtidos na base de dados Web of Science (WoS) Core Collection. Todos os documentos publicados entre 1975 e 2019 foram incluídos na análise. Os dados exportados da WoS viabilizaram acesso a amplos detalhes da literatura relacionada à genética oftálmica, incluindo países, instituições, autores, citações e palavras-chave. Mapas de rede cienciométrica foram criados por meio de software gratuito, com base em palavras-chave e em coautorias de países e instituições. As contribuições globais dos países para a literatura sobre genética oftálmica foram apresentadas em gráfico. Resultados: a busca por pesquisas revelou um total de 2.322 documentos cuja maioria eram artigos originais (75,75%). Os EUA foram o país que mais produziu artigos sobre o tema, com 45,39% de todos os documentos em pesquisa genética oftálmica; ele foi seguido pelo Reino Unido, Alemanha, China e França. A Universidade da Pensilvânia foi a instituição que mais contribuiu para a literatura (5,25%), e foi seguida pela University College London e pelo Moorfields Eye Hospital. A média de citações por item foi de 29,4. As palavras-chave mais usadas em um período de 40 anos foram 'família', 'célula', 'fotorreceptor' e 'expressão'. Conclusões: Os EUA e o Reino Unido dominaram a pesquisa em genética oftálmica. Após 2010, observou-se um aumento substancial no número de documentos publicados nessa área.

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Um grande número de estudos indica que a diversidade genética entre populações pode levar a diferenças em múltiplos aspectos como: inflamação crônica, resposta a antígenos e no padrão de mutações. Estas diferenças seriam parcialmente responsáveis por alterações em fenótipos e na suscetibilidade a doenças. O carcinoma de pulmão de células não pequenas (CPCNP) possui fortes componentes genéticos e ambientais, sendo o seu principal fator de risco o tabagismo. Segundo dados de 2012, o câncer de pulmão foi o tipo de câncer mais incidente no mundo, e foi observado nos Estados Unidos, uma maior incidência em afrodescendentes. Já o melanoma tem como seu principal fator de risco a exposição excessiva à radiação solar ultravioleta (UV), além do histórico familiar. Neste cenário, torna-se relevante avaliar a relação entre ancestralidade e o seu impacto na saúde. Para isso, o presente trabalho busca elucidar esta relação em casos de melanoma e CPCNP e contribuir para a identificação de possíveis marcadores. Dados de transcriptoma, sequenciamento completo de exoma e clínicos foram obtidos a partir do The Cancer Genome Atlas (TCGA). Com o intuito de inferir ancestralidade individual foi utilizado o software Admixture e foi construído um pipeline automatizado através do gerenciador Snakemake. Além disso, também foi avaliado o infiltrado inflamatório, expressão gênica, perfil mutacional somático e assinatura mutacional. A integração destes dados foi realizada através da aplicação dos modelos de predição, LASSO e Elastic Net. Em relação ao infiltrado inflamatório, assinatura mutacional, perfil mutacional somático e expressão gênica, foram observadas diferenças importantes entre os grupos avaliados, independentemente do tipo de tumor. Constatou-se, em indivíduos com ancestralidade africana, uma maior frequência de mutações em TP53 e maiores níveis de linfócitos T e B. Em relação à ancestralidade europeia, observou-se maiores níveis de monócitos e macrófagos M2. A aplicação dos modelos de predição foi capaz de identificar genes importantes, destacando-se: MASTL, TP73, FAAH, PWP2, AHRR, COL22A1, ACBD3, PLEK2, EEPD1 e ASH2L. Como um todo, este estudo reforça a importância da inferência de ancestralidade individual e sugere diferenças importantes em cada um dos grupos, podendo impactar diretamente na sobrevida de pacientes

A large number of studies indicates that genetic diversity between populations can lead to differences in multiple aspects such as: chronic inflammation, response to antigens and pattern of mutations. These differences would be partly responsible for changes in phenotypes and disease susceptibility. The non-small cell lung carcinoma (NSCLC). has strong genetic and environmental components, and its main risk factor is smoking. According to data from 2012, lung cancer was the most common type of cancer in the world, and it was observed in the United States a higher incidence in Afro-descendants. On the other hand, melanoma's main risk factor is excessive exposure to ultraviolet (UV) solar radiation, in addition to the family history. In this scenario, it becomes relevant to assess the relationship between ancestry and its impact on health. To this end, the present study seeks to elucidate this relationship in cases of melanoma and NSCLC and to contribute to the identification of possible markers. Transcriptome, whole exome sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA). In order to infer individual ancestry, the software Admixture was used, and an automated pipeline was built using Snakemake. In addition, inflammatory infiltrate, gene expression and somatic mutational profile and mutational signature were also evaluated. The integration of these data was accomplished through the application of regression models, LASSO and Elastic Net. Regarding the inflammatory infiltrate, mutational signature, somatic mutation profile and gene expression, important differences were observed between the groups evaluated, regardless of the type of tumor. It was found, in individuals with African ancestry, a higher frequency of mutations in TP53 and higher levels of T and B lymphocytes. In relation to European ancestry, higher levels of monocytes and macrophages M2 were observed. The use of regression models was able to identify important genes, highlighting: MASTL, TP73, FAAH, PWP2, AHRR, COL22A1, ACBD3, PLEK2, EEPD1 e ASH2L. As a whole, this study reinforces the importance of the inference of individual ancestry and suggests important differences in each of the groups, which may directly impact on patient survival

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Resumen El presente artículo es una revisión de las reflexiones éticas sobre temas de genética y manipulación genética que se han publicado en 20 años de Acta Bioethica. Se identifican los siguientes temas relevantes en el diálogo bioético: evaluación de riesgos, inequidad, pérdida de la biodiversidad, eugenesia, definir los límites entre natural y artificial, diálogo entre detractores y promotores de la biotecnología, desafíos en el cuidado de la salud, manejo de la información y confidencialidad. Se concluye que la bioética puede actuar como intermediaria entre los diversos interlocutores ante los problemas que se suscitan al aplicar la tecnología a la vida, permitiendo reconocer y llegar a consensos para enfrentar con responsabilidad las diferencias en temas de equidad, autonomía y el balance entre riesgos y beneficios. Las reflexiones en Acta Bioethica sobre genómica son similares a las de otras revistas, solo que el énfasis es en la región latinoamericana. En veinte años de reflexión, los desafíos siguen siendo los mismos, aunque el énfasis está cambiando de la prevención y rechazo en cuanto a los riesgos de la modificación genética, a la regulación de la tecnología de ingeniería genética, que va perfeccionándose cada vez más. En cuanto a los beneficios, la medicina genómica siempre ha generado más expectativas que realidades, sin lograr demostrar eficacia en ensayos clínicos. Con las nuevas técnicas de edición genómica, se amplían aún más las expectativas de mejores intervenciones, pero aumenta la preocupación de que se realicen modificaciones genéticas sin finalidad terapéutica, afectando al equilibrio social y ecológico.

Abstract This article reviews ethical reflections about genetic research and genetic manipulation published in 20 years of Acta Bioethica. The following relevant topics are identified in bioethics dialogue: risks evaluation, inequity, loss of biodiversity, eugenics, definition of limits between artificial and natural, dialogue between detractors and promoters of biotechnology, challenges in health care, information and confidentiality management. Reflections consider that bioethics can act as mediator among diverse stakeholders affronting the problems that arise when applying technology to life, allowing to recognize and to reach consensus for solving differences in equity, autonomy and the balance of risks and benefices. The reflections in Acta Bioethica are similar to those of other journals, but with emphasis in the Latin American region. In twenty years of reflection, the challenges are similar, but the emphasis is changing from preventing to the avoidance of actual risks of genetic modifications, which demands regulation of genetic engineering, taking into account that it is more effective than before. Among the benefits, genomic medicine has always generated more expectations than actual therapy with problems in demonstrating efficacy in clinical trials. With the new technique of genomic edition, there are even more expectations for enhancing therapeutic approaches, but worries increase about using genetic modifications without therapeutic aim and interventions that affect the social and ecological equilibrium.

Resumo O presente artigo é uma revisão das reflexões éticas sobre temas de genética e manipulação genética que foram publicadas em 20 anos de Acta Bioethica. Os seguintes temas de importância para o diálogo bioético foram identificados: avaliação de riscos, inequidade, perda da biodiversidade, eugenia, definir os limites entre natural e artificial, diálogo entre opositores e defensores da biotecnologia, desafios em cuidados à saúde, manejo da informação e confidencialidade. Concluiu-se que a bioética pode atuar como intermediaria entre os diversos interlocutores ante os problemas que aparecem ao aplicar a tecnologia à vida, permitindo reconhecer e alcançar consensos para enfrentar com responsabilidade as diferenças em temas de equidade e autonomia, e o equilíbrio entre riscos e benefícios. As reflexões na Acta Bioethica sobre genômica são similares às de outras revistas, mas com ênfase na região latino-americana. Em vinte anos de reflexão, os desafios seguem sendo os mesmos, ainda que a ênfase esteja mudando da prevenção e repúdio quanto aos riscos da modificação genética, à regulação da tecnologia de engenharia genética, que se aperfeiçoa cada vez mais. Quanto aos benefícios, a medicina genômica sempre gerou mais expectativas que realidades, sem conseguir demonstrar eficácia em ensaios clínicos. Com as novas técnicas de edição genômica, ampliam-se ainda mais as expectativas de melhores intervenções, mas aumenta a preocupação de que se realizem modificações genéticas sem finalidade terapêutica, afetando o equilíbrio social e ecológico.

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In the next decades, gene editing technologies are expected to be used in the treatment and prevention of human diseases. Yet, the future uses of gene editing in medicine are still unknown, including its applicability and effectiveness to the treatment and prevention of infectious diseases, cancer, and monogenic and polygenic hereditary diseases. This study aims to address this gap by analyzing the views of over 1,000 gene editing-related researchers from all over the world. Some of our survey results show that, in the next 10 years, DNA double-strand breaks are expected to be the main method for gene editing, and CRISPR-Cas systems to be the mainstream programmable nuclease. In the same period, gene editing is expected to have more applicability and effectiveness to treat and prevent infectious diseases and cancer. Off-targeting mutations, reaching therapeutic levels of editing efficiency, difficulties in targeting specific tissues in vivo, and regulatory and ethical challenges are among the most relevant factors that might hamper the use of gene editing in humans. In conclusion, our results suggest that gene editing might become a reality to the treatment and prevention of a variety of human diseases in the coming 10 years. If the future confirms these researchers' expectations, gene editing could change the way medicine, health systems, and public health deal with the treatment and prevention of human diseases.

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The purpose of this article is to analyze the possibilities that the hegemonic medical model will continue to prevail in the future or if significant changes will take place. The discussion will take as a starting point the characteristics and current functions of the hegemonic medical model, and reexamine them through a look at advancements in artificial intelligence, genetic research, and robotics in health-illness-care-prevention processes. The analysis takes on issues such as possible increases in life expectancy, what is needed to "cure old age," as well as processes that are modifying the doctor-patient relationship. It is concluded that although significant changes are taking place, the characteristics and functions of the hegemonic medical model remain unmoved.

El objetivo de este texto es analizar la posibilidad futura de que el modelo médico hegemónico siga perpetuándose o se generen cambios significativos. Para ello, se parte de las características y funciones actuales del modelo médico hegemónico y se las observa a través de algunos de los aportes de la inteligencia artificial, de las investigaciones genéticas y de la robótica, referidas a procesos de salud-enfermedad-atención-prevención, entre los que se analizan las posibilidades de fuertes incrementos en la esperanza de vida, las necesidades de "curar la senectud", así como los procesos que están modificando la relación médico-paciente, llegando a la conclusión de que si bien se observan algunas modificaciones sustantivas, las características y funciones del modelo médico hegemónico siguen siendo las mismas.

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ETHNOPHARMACOLOGICAL RELEVANCE: The Peruvian Amazon holds more than 1000 plant species with commercial potential and the national sales of natural products derived from medicinal and aromatic plants have exceeded $ 400 million per year. Research and development activities carried out on the genetic and biochemical composition of Peruvian flora have to abide by national and international regulations, such as the Nagoya Protocol (NP). AIM OF THE STUDY: The aim of this paper is to describe the implications of the current implementation of the NP in Peru for performing research on national genetic resources. MATERIALS AND METHODS: A review of the current legal framework and status of the NP in Peru was performed accompanied by first-hand experience undertaken by submitting a request for access to genetic resources related to wild continental species. RESULTS: So far, Peru has issued 16 Internationally Recognized Certificates of Compliance (IRCCs) through 2 of the identified National Authorities. Some of the difficulties and challenges observed have to do with the degree of effective implementation of the Access and Benefit-Sharing (ABS) system, the fact that the application process is not sufficiently clear, and the wide gap between this formal system and what occurs informally outside of it. In response to this, training and implementation projects have been launched and a new law on the access to genetic resources has been proposed. CONCLUSIONS: The difficulties observed still represent an obstacle to scientific research and the development of new commercial products based on Peruvian traditional knowledge and genetic resources. Although improvements have been made to the ABS framework, there remain major challenges to encouraging and ascertaining the equitable and sustainable use of Peru's biodiversity.

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RESUMEN El objetivo de este texto es analizar la posibilidad futura de que el modelo médico hegemónico siga perpetuándose o se generen cambios significativos. Para ello, se parte de las características y funciones actuales del modelo médico hegemónico y se las observa a través de algunos de los aportes de la inteligencia artificial, de las investigaciones genéticas y de la robótica, referidas a procesos de salud-enfermedad-atención-prevención, entre los que se analizan las posibilidades de fuertes incrementos en la esperanza de vida, las necesidades de "curar la senectud", así como los procesos que están modificando la relación médico-paciente, llegando a la conclusión de que si bien se observan algunas modificaciones sustantivas, las características y funciones del modelo médico hegemónico siguen siendo las mismas.

ABSTRACT The purpose of this article is to analyze the possibilities that the hegemonic medical model will continue to prevail in the future or if significant changes will take place. The discussion will take as a starting point the characteristics and current functions of the hegemonic medical model, and reexamine them through a look at advancements in artificial intelligence, genetic research, and robotics in health-illness-care-prevention processes. The analysis takes on issues such as possible increases in life expectancy, what is needed to "cure old age," as well as processes that are modifying the doctor-patient relationship. It is concluded that although significant changes are taking place, the characteristics and functions of the hegemonic medical model remain unmoved.

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Introducción: La irrupción de la investigación genética en la esfera del deporte ha permitido la localización en el genoma de un considerable número de genes implicados en el rendimiento deportivo y, con ello, el desarrollo de tecnologías genéticas orientadas a la identificación del potencial atlético en niños, cuya aplicación, dada su relativa juventud, debe ser sometida al escrutinio de la comunidad científica desde el prisma de la ética. Objetivo: Evaluar, desde una perspectiva ética, el uso de tecnologías genéticas en la identificación del potencial atlético en niños. Material y métodos: Para la elaboración de la presente revisión, además de la consulta de publicaciones no seriadas, se efectuó una pesquisa en la base de datos Scopus. Resultados: En la actualidad se conocen más de 200 marcadores genéticos relacionados con la predisposición para la aptitud física y al menos 120 vinculados directamente con el rendimiento atlético de élite, información que ha sido utilizada por numerosas compañías para desarrollar los llamados Tests Directos al Consumidor, que pretenden identificar el potencial atlético en niños a partir de su genotipo, sin necesidad de consultar a un especialista. Conclusiones: El uso de tecnologías genéticas en la determinación del potencial atlético en niños no solo viola el espíritu del deporte, sino que también tiene el potencial de causar efectos nocivos en el individuo a nivel psicológico y social; razones por las que es éticamente inadmisible su uso en futuros atletas(AU)

Introduction: The emergence of genetic research in the field of sports has allowed the location of the genome of a considerable number of genes involved in sports performance and thus, the development of genetic technologies aimed at the identification of the athletic potential in children whose application, given its relative youth, should be subject to the review of the scientific community through the prism of ethics. Objective: To evaluate, from an ethical perspective, the use of genetic technologies in the identification of the athletic potential in children. Materials and methods: A search in Scopus database and the consultation of non-serial publications were carried out for the development of this review. Results: Currently, there are more than 200 genetic markers related to the predisposition for physical fitness and, at least, 120 of them are directly linked to elite athletic performance. This information has been used by many companies to develop the so-called Direct-to-Consumer Tests, which aim to identify the athletic potential in children from their genotype, without any need to consult a specialist. Conclusions: The use of genetic technologies in the determination of athletic potential in children not only violates the spirit of sport, but also has the potential to cause harmful effects on the individual at psychological and social levels, reasons why their use is ethically inadmissible in future athletes(AU)

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