La importancia de la genética en el estudio de la hipertrigliceridemia / The importance of genetics in the study of hypertriglyceridemia

La hipertrigliceridemia engloba un conjunto de trastornos lipídicos comunes en la práctica clínica, generalmente definidos como una concentración superior a 150mg/dL en ayunas. Existen diversas clasificaciones de la gravedad de la hipertrigliceridemia en función de sus valores séricos, considerándose por norma general moderada cuando los niveles son inferiores a 500mg/dL y severa cuando son mayores de 1.000mg/dL. Su importancia radica en su asociación con otras alteraciones del perfil lipídico, contribuyendo al aumento del riesgo cardiovascular y de pancreatitis aguda, fundamentalmente con concentraciones superiores a 500mg/dL.(AU)

Hypertriglyceridemia encompasses a set of lipid disorders common in clinical practice, generally defined as a fasting concentration above 150mg/dL. There are various classifications of the severity of hypertriglyceridaemia based on serum values, with levels generally considered moderate when below 500mg/dL and severe when above 1000mg/dL. Its importance lies in its association with other alterations in the lipid profile, contributing to increased cardiovascular risk and increased risk of acute pancreatitis, mainly with concentrations above 500mg/dL.(AU)

Enfermedad de Hirschsprung no sindrómica por variante en el gen RET / Non-syndromic Hirschsprung’s disease as a result of a RET gene variant

Introducción: La enfermedad de Hirschsprung (EH) se caracterizapor la ausencia de células ganglionares en los plexos submucoso y mientérico del intestino grueso, resultante de deficiencias en la migracióny diferenciación de las células de la cresta neural entérica durante laembriogénesis. Es una condición multifactorial, con más de 11 genesidentificados en su patogénesis, incluyendo el protooncogén RET.Caso clínico: Se presenta el caso de dos hermanos con EH de colontotal, cuyo padre también padeció la enfermedad, y en quien se encontróuna variante potencialmente patogénica en el gen RET.Comentarios: El diagnóstico prenatal mediante pruebas genéticaspermite decisiones informadas y la planificación de cuidados para elneonato afectado, reduciendo demoras en el diagnóstico y tratamiento,y minimizando las complicaciones a largo plazo. La identificación demutaciones como la variante en el gen RET destaca la importancia delenfoque genético en la comprensión y manejo de la EH.(AU)

Introduction: Hirschsprung’s disease (HD) is characterized by theabsence of ganglion cells in the submucosal and myenteric plexuses ofthe colon as a result of disorders in the migration and differentiationof enteric neural crest cells during embryogenesis. It is a cross-factorcondition, with more than 11 genes identified in its pathogenesis, including the RET proto-onco gene.Case report: We present the case of two siblings with total colonHD where a potentially pathogenic variant of the RET gene was found.Their father also had this condition.Discussion: Prenatal diagnosis through genetic testing allows forinformed decisions and care planning for the newborn, thus reducin delayed diagnosis and treatment, and minimizing long-term complications. Mutations such as the RET gene variant highlight the importanceof the genetic approach in understanding and managing HD.(AU)

Genetic and morphological characterization of a new genotype of nervous necrosis virus circulating among Nile tilapia in the south of Egypt

Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis in freshwater and marine fishes. In this study, NNV circulating among wild and farmed Nile tilapia (Oreochromis niloticus) was genetically and morphologically characterized using reverse transcription polymerase chain reaction (RT-PCR), sequencing analysis, and transmission electron microscopy (TEM). Brain, eye, and other organ (spleen, kidney, heart, and liver) specimens were collected from 87 wild (66) and farmed (21) Nile tilapia fish during their adult or juvenile stage at different localities in Qena and Sohag governorates in southern Egypt. Among them, 57/87 fish showed suspected NNV clinical signs, and 30/87 were healthy. The results revealed that NNV was detected in 66 out of 87 fish (58.62% in the wild and 17.24% in farmed Nile tilapia by RT-PCR), and the prevalence was higher among diseased (55.17%) than in healthy (20.69%) fish. NNV was detected in the brain, eye, and other organs. Using TEM, virion size variations based on the infected organs were observed. Nucleotide sequence similarity indicated that NNVs had a divergence of 75% from other fish nodaviruses sequenced in Egypt and worldwide. Phylogenetic analysis distinguished them from other NNV genotypes, revealing the emergence of a new NNV genotype in southern Egypt. In conclusion, NNV is circulating among diseased and healthy Nile tilapia, and a new NNV genotype has emerged in southern Egypt. (AU)

The construction of genetics teaching resources related to colour blindness and their application in genetics teaching.

Red-green colour blindness is a classic example for the teaching of X-linked recessive inheritance in genetics course. However, there are lots of types of color vision deficiencies besides red-green colour blindness. Different color vision deficiencies caused by different genes may have different modes of inheritance. In recent years, many research achievements on colour blindness have been made. These achievements could be used as teaching resources in genetics course. Here, we summarize the construction of genetics teaching resources related to colour blindness and their application in genetics teaching in several chapters such as introduction, cellular and molecular basis of genetics, sex-linked inheritance, chromosomal aberration, gene mutation and advances in genetics. Teacher could use the resources in class or after class with different teaching methods such as questioning teaching method and task method. It may expand students' academic horizons and inspire students' interest in genetics besides grasping basic genetic knowledge.

Ocorrência rara de amiloidose por transtirretina na segunda década de vida / Rare occurrence of transthyretin amyloidosis in the second decade of life

INTRODUÇÃO: Sendo p.V50M e p.V142I as variantes mais comuns associadas à amiloidose por transtirretina hereditária (ATTRh), pode haver uma errônea correlação de que a doença se manifeste apenas em idosos já que a apresentação clínica em seus portadores geralmente se inicia tardiamente, em meia idade e acima de 60 anos, respectivamente. Entretanto, existem outras variantes que podem determinar quadro clínico mais grave e precoce. Descrevemos uma série de casos com início em idade inferior a 25 anos associados à identificação de variante rara no gene TTR. MÉTODOS: Estudo observacional de série de casos RESULTADOS: Três pacientes (p) masculinos, aparentados, portadores de ATTRh confirmada por teste molecular positivo para a variante patogênica p.F64S, com idade média de apresentação clínica de 19±3 anos. Características basais dos p expressas na tabela 1. Todos os p apresentavam fenótipo misto, sendo portadores de polineuropatia grave, disautonomia (expressa por disfunção erétil, hipotensão e alterações digestivas) e cardiopatia em graus variáveis, mais evidente no p com instalação da doença há mais tempo. Espessura média do septo de 15,6±4 mm e de 13±3 mm, da parede posterior. Um p apresentou derrame pericárdico volumoso recorrente. Nenhum óbito ocorreu durante o seguimento. Todos os p receberam tratamento específico para amiloidose: o caso índice foi submetido a transplante hepático, outro está recebendo um silenciador gênico (eplontersen em protocolo clínico) e, o último, em uso de tafamidis 20mg. DISCUSSÃO E CONCLUSÃO: descrevemos 3 p aparentados, que apresentaram os primeiros sintomas de ATTRh aos 20 anos de idade com fenótipo misto (polineuropatia e cardiopatia), determinada pela variante p.F64S. Esta variante é muito rara e encontramos 7 casos descritos na Literatura, todos muito jovens que apresentaram fenótipo predominante de polineuropatia, mas a maioria com cardiopatia associada. A variante p.V50M também pode ocorrer em jovens na forma precoce da doença, porém isto ocorre em torno da terceira década de vida. Conclui-se que a amiloidose não deve ser encarada como uma doença exclusiva da população idosa. A forma hereditária pode ocorrer em p mais jovens e a idade de início do quadro dependerá da variante encontrada. Deve-se, portanto, considerar amiloidose como diagnóstico diferencial das hipertrofias ventriculares em jovens.

Agregación familiar en el síndrome de colon irritable en pacientes mexicanos. Un estudio de casos y controles / Familial aggregation in Irritable Colon Syndrome in Mexican patients. A case-control study

Objetivo: Determinar la existencia de un patrón familiar de agregación del síndrome de intestino irritable (SII). Diseño: Es un estudio de casos y controles con proporción 1:2, llevado a cabo en una consulta externa de medicina general-familiar. Participantes: Hombres y mujeres de 18 a 60 años. Participaron 40 casos con SII de acuerdo con criterios de Roma IV, y 80 controles integrados por familiares sin alguna enfermedad gastrointestinal. Las mediciones principales fueron variables sociodemográficas, algún evento estresante relacionado, patrón evacuatorio predominante y patrón de repetición familiar para SII. Se analizaron los datos con estadísticas descriptivas e inferenciales. X2 para datos categóricos, estimación de odds ratio (OR) con intervalo de confianza (IC) 95%. Fue aprobado por el comité de ética institucional. Resultados: Hubo repetición del patrón de presentación del SII en familiares principalmente de primer grado. Fue mayor el riesgo de padecer este síndrome cuando el padre lo reportó (OR de 11,2; IC 95% 2-100,1), que cuando la madre lo presentó (OR 3,7; IC 95% 1,4-9,9), o hermano(a) (OR 2,8; IC 95% 1,1-6,6). En ambos grupos, el familiar que más frecuentemente presentaba SII fue en la línea colateral (hermano/a) (37,5% en los casos vs. 17,5% en los controles [p=0,023]). En ambos grupos el género predominante fue el femenino con 80,0% en los casos y 57,5% en los controles. Conclusión: Existe en la población mexicana un patrón de agregación familiar. La enfermedad es más frecuente en familiares en primer grado. Es importante dilucidar si quien desempeña el rol más importante en SII es el trasfondo genético o el entorno familiar.(AU)

Objective: To determine a family aggregation pattern of Irritable Bowel Syndrome (IBS). Design: it is a case-control study with a 1.2 ratio. Setting. External consultation of a general family medicine practice. Participants: men and women from 18 to 60 years old. Cases (40): people with IBS according to the Rome IV criteria, and Controls (80): relatives without gastrointestinal disease. Main measurements. Sociodemographic variables, related stressful events, predominant evacuation patterns, and family repetition patterns for IBS. Data were analyzed with descriptive and inferential statistics. Chi-square for categorical data (< p.05 as significant) estimate of ORs with 95% confidence interval. The institutional ethics committee approved it. Results: The IBS presentation pattern was repeated in relatives, mainly first-degree. The risk of suffering from IBS was higher when the father reported it (OR 11.2 (95% CI; 1.2 -100.1), than the mother OR 3,7 (95% CI; 1.4 – 9.9), sibling OR 2.8 (95% CI; 1.1 – 6.6. In both groups, the relative who most frequently presented IBS was in the collateral line (sibling) (37.5% in cases vs. 17.5% in controls (p=0.023). In both groups, the predominant gender was female, with 80. 0% in cases and 57.5% in controls. Conclusion: SII has a familial recurrence pattern in the Mexican population. The disease is more frequent in first-degree relatives. It is important to elucidate the importance of the role that plays genetic background vs. the influence of the family environment in SII.(AU)

The legacy of language: What we say, and what people hear, when we talk about genomics.

The way we "talk" about genetics plays a vital role in whether public audiences feel at ease in having conversations about it. Our research explored whether there was any difference between "what we say" and "what people hear" when providing information about genetics to community groups who are known to be missing from genomics datasets. We conducted 16 focus groups with 100 members of the British public who had limited familiarity with genomics and self-identified as belonging to communities with Black African, Black Caribbean, and Pakistani ancestry as well as people of various ancestral heritage who came from disadvantaged socio-economic backgrounds. Participants were presented with spoken messages explaining genomics and their responses to these were analyzed. Results indicated that starting conversations that framed genomics through its potential benefits were met with cynicism and skepticism. Participants cited historical and present injustices as reasons for this as well as mistrust of private companies and the government. Instead, more productive conversations led with an acknowledgment that some people have questions-and valid concerns-about genomics, before introducing any of the details about the science. To diversify genomic datasets, we need to linguistically meet public audiences where they are at. Our research has demonstrated that everyday talk about genomics, used by researchers and clinicians alike, is received differently than it is likely intended. We may inadvertently be further disengaging the very audiences that diversity programs aim to reach.

Mendel did not study common, naturally occurring phenotypes.

Modern genetics research increasingly reveals that what is commonly termed Mendelian genetics occurs rarely in nature, especially with regard to the effects that genetic variation exerts on human characteristics. It has been argued that an inappropriate emphasis on Mendel's work could distort the public understanding of genetics and indeed in the UK Mendel has been completely dropped from the official school syllabus. There is a widespread misunderstanding that Mendel studied common phenotypes such as height and colour in individual pea plants. In fact, he studied a handful of specially selected phenotypes which he observed to be always dichotomous in 22 specially bred varieties of pea and studied crosses between individuals from these different varieties. This approach enabled him to study a small number of phenotypes which did in fact exhibit truly Mendelian transmission. Modern molecular genetic studies have now demonstrated that these phenotypes result from loss of function variants which result in markedly reduced activity of specific proteins and which hence have recessive effects. Understanding that Mendel studied the effects of loss of function mutations in crosses between artificially bred varieties, rather than naturally occurring variation in a population, could allow his work to continue to be taught as part of a modern genetics curriculum.

Genética y genómica de la longevidad y el envejecimiento / Genetics and genomics of longevity and aging

El envejecimiento y la longevidad son procesos que involucran una serie de factores genéticos, bioquímicos y ambientales. En esta revisión se tratan algunas cuestiones sobre estos dos procesos biológicos y epigenéticos. Se presentan los genes más importantes en estos procesos, así como se ejemplifican enfermedades que presentan un aceleramiento o falla en la longevidad y el envejecimiento. Se usa el análisis inteligente de datos para hallar interacciones de proteínas/genes que expliquen estos dos fenómenos biológicos.

Aging and longevity are processes that involve a series of genetic, biochemical and environmental factors. This review addresses some issues about these two biological and epigenetic processes. The most important genes in these processes are presented, as well as diseases that present an acceleration or failure in longevity and aging. Intelligent data analysis is used to find protein/gene interactions that explain these two biological phenomena.

Genes, genomes, and developmental process.

The view advanced by Madole & Harden falls back on the dogma of a gene as a DNA sequence that codes for a fixed product with an invariant function regardless of temporal and spatial contexts. This outdated perspective entrenches the metaphor of genes as static units of information and glosses over developmental complexities.

Genetics can inform causation, but the concepts and language we use matters.

Madole & Harden describe how genetics can be used in a causal framework. We agree with many of their opinions but argue that comparing within-family designs to experiments is unnecessary and that the proposed influence of genetics on behavior can be better described as inus conditions.

Meeting counterfactual causality criteria is not the problem.

Counterfactual causal interpretations of family genetic effects are appropriate, but neglect an important feature: Provision of unique information about expected outcomes following an independent decision, such as a decision to intervene. Counterfactual causality criteria are unlikely to resolve controversies about behavioral genetic findings; such controversies are likely to continue until counterfactual inferences are translated into interventional hypotheses and designs.

Increasing the use of functional and multimodal genetic data in social science research.

Genetic studies in the social sciences could be augmented through the additional consideration of functional (transcriptome, methylome, metabolome) and/or multimodal genetic data when attempting to understand the genetics of social phenomena. Understanding the biological pathways linking genetics and the environment will allow scientists to better evaluate the functional importance of polygenic scores.

Evelyn M. Witkin (1921-2023).

Pioneer of cell mutagenesis and DNA repair research.