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.

Muller and mutations: mouse study of George Snell (a postdoc of Muller) fails to confirm Muller's fruit fly findings, and Muller fails to cite Snell's findings.

In 1931, Hermann J. Muller's postdoctoral student, George D. Snell (Nobel Prize recipient--1980) initiated research to replicate with mice Muller's X-ray-induced mutational findings with fruit flies. Snell failed to induce the two types of mutations of interest, based on fly data (sex-linked lethals/recessive visible mutations) even though the study was well designed, used large doses of X-rays, and was published in Genetics. These findings were never cited by Muller, and the Snell paper (Snell, Genetics 20:545-567, 1935) did not cite the 1927 Muller paper (Muller, Science 66:84, 1927). This situation raises questions concerning how Snell wrote the paper (e.g., ignoring the significance of not providing support for Muller's findings in a mammal). The question may be raised whether professional pressures were placed upon Snell to downplay the significance of his findings, which could have negatively impacted the career of Muller and the LNT theory. While Muller would receive worldwide attention, and receive the Nobel Prize in 1946 "for the discovery that mutations can be induced by X-rays," Snell's negative mutation data were almost entirely ignored by his contemporary and subsequent radiation genetics/mutation researchers. This raises questions concerning how the apparent lack of interest in Snell's negative findings helped Muller professionally, including his success in using his fruit fly data to influence hereditary and cancer risk assessment and to obtain the Nobel Prize.

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.

Comparative neurogenetics of dog behavior complements efforts towards human neuropsychiatric genetics.

Domestic dogs display a wide array of heritable behaviors that have intermediate genetic complexity thanks to a long history of human-influenced selection. Comparative genetics in dogs could address the scarcity of non-human neurogenetic systems relevant to human neuropsychiatric disorders, which are characterized by mental, emotional, and behavioral symptoms and involve vastly complex genetic and non-genetic risk factors. Our review describes the diverse behavioral "phenome" of domestic dogs, past and ongoing sources of behavioral selection, and the state of canine behavioral genetics. We highlight two naturally disordered behavioral domains that illustrate how dogs may prove useful as a comparative, forward neurogenetic system: canine age-related cognitive dysfunction, which can be examined more rapidly given the attenuated lifespan of dogs, and compulsive disorders, which may have genetic roots in purpose-bred behaviors. Growing community science initiatives aimed at the companion dog population will be well suited to investigating such complex behavioral phenotypes and offer a comparative resource that parallels human genomic initiatives in scale and dimensionality.