58 Integrating Quantitative Genetics and Epidemiology: Why Selection Against Infectious Diseases Is More Promising Than We Think

Pathogens have profound effects on livestock. The low heritabilities of individual binary disease status suggest limited prospects for genetic improvement. However, a proper quantitative genetic theory for infectious diseases, including transmission dynamics, is currently lacking. Here we present a quantitative genetic theory for endemic infectious diseases, focussing on the genetic factors that determine the prevalence (P; the mean fraction of the population that is infected). We present simple expressions for breeding values and genetic parameters for the prevalence. Without genetic variation in infectiousness, breeding values for prevalence are a factor 1/P greater than the ordinary breeding values for individual binary disease status (0/1). Hence, even though prevalence is the simple average of individual binary disease status, breeding values for prevalence show much greater variation than our ordinary breeding values. This implies that the genetic variance that determines the potential response of prevalence to selection is largely due to indirect genetic effects (IGE), and thus hidden to ordinary genetic analysis and selection. Hence, the genetic variance that determines the potential of livestock populations to respond to selection must be much greater than currently believed, particularly at low prevalence. We evaluated this implication using simulation of endemics following standard methods in epidemiology. Results show that response of prevalence to selection increases very strongly when prevalence decreases, and is much greater than predicted by our ordinary breeding values. These results supports our theoretical findings, and show that selection against infectious diseases is much more promising than currently believed.

The quantitative genetics of the prevalence of infectious diseases: hidden genetic variation due to Indirect Genetic Effects dominates heritable variation and response to selection

Infectious diseases have profound effects on life, both in nature and agriculture. However, a quantitative genetic theory of the host population for the endemic prevalence of infectious diseases is almost entirely lacking. While several studies have demonstrated the relevance of transmission of infections for heritable variation and response to selection, current quantitative genetics ignores transmission. Thus, we lack concepts of breeding value and heritable variation for endemic prevalence, and poorly understand response of endemic prevalence to selection. Here we integrate quantitative genetics and epidemiology, and propose a quantitative genetic theory for the basic reproduction number R0 and for the endemic prevalence of an infection. We first identify the genetic factors that determine the prevalence. Subsequently we investigate the population level consequences of individual genetic variation, for both R0 and the endemic prevalence. Next, we present expressions for the breeding value and heritable variation, for endemic prevalence and individual binary disease status, and show that these depend strongly on the prevalence. Results show that heritable variation for endemic prevalence is substantially greater than currently believed, and increases strongly when prevalence decreases, while heritability of disease status approaches zero. As a consequence, response of the endemic prevalence to selection for lower disease status accelerates considerably when prevalence decreases, in contrast to classical predictions. Finally, we show that most heritable variation for the endemic prevalence is hidden in indirect genetic effects, suggesting a key role for kin-group selection in the evolutionary history of current populations and for genetic improvement in animals and plants.

KoT: an automatic implementation of the K/θ method for species delimitation

K/θ is a method to delineate species that rests on the calculation of the ratio between the average distance K separating two putative species-level clades and the genetic diversity θ of these clades. Although this method is explicitly rooted in population genetic theory, it was never benchmarked due to the absence of a program allowing automated analyses. For the same reason, its application by hand was limited to small datasets of a few tens of sequences. We present an automatic implementation of the K/θ method, dubbed KoT (short for "K over Theta"), that takes as input a FASTA file, builds a neighbour-joining tree, and returns putative species boundaries based on a user-specified K/θ threshold. This automatic implementation avoids errors and makes it possible to apply the method to datasets comprising many sequences, as well as to test easily the impact of choosing different K/θ threshold ratios. KoT is implemented in Haxe, with a javascript webserver interface freely available at https://eeg-ebe.github.io/KoT/ .

Atuação do enfermeiro na assistência a pessoas esquizofrênicas

A esquizofrenia é considerada pela teoria genética uma desordem hereditária, e pode estar associada também a fatores ambientais como uso de drogas, tabagismo e doenças autoimunes. As perturbações da consciência, comportamento, percepção, emoção e pensamento são sinais e sintomas que representa os transtornos mentais. Compreender a atuação do enfermeiro na assistência a pessoas esquizofrênicas. Pesquisa descritiva e investigativa de revisão, utilizou de artigos publicados em língua portuguesa e inglesa, nos anos de 2011 a 2019, tendo como fonte as bases de dados: LILACS, BDNEF, MEDLINE, INDEXPSI, SCIELO e ABRASME. O foco do enfermeiro que atua em saúde mental deve ser a promoção da saúde das pessoas portadoras de transtornos e família, para uma melhor qualidade de vida do paciente e a prevenção de agravos, de forma holística, integral e humanizada. É dever do enfermeiro orientar o paciente e família a respeito do tratamento e dúvidas relevantes, transmitindo tranquilidade e segurança. Uma assistência humanizada é necessária, como também um comprometimento da equipe para com os pacientes e família, uma escuta efetiva e a comunicação são indispensáveis no acolhimento da pessoa.Descritores: Saúde Mental, Esquizofrenia, Cuidado, Enfermagem. Nurse's role in assisting schizophrenic peopleAbstract: Schizophrenia is considered by genetic theory to be a hereditary disorder, and it may also be associated with environmental factors such as drug use, smoking and autoimmune diseases. Disorders of consciousness, behavior, perception, emotion and thinking are signs and symptoms that represent mental disorders. Understand the role of nurses in assisting schizophrenic people. Descriptive and investigative review research, used articles published in Portuguese and English, in the years 2011 to 2019, having as source the databases: LILACS, BDNEF, MEDLINE, INDEXPSI, SCIELO and ABRASME. The focus of nurses who work in mental health should be to promote the health of people with disorders and their families, for a better quality of life for the patient and the prevention of injuries, in a holistic, comprehensive and humanized way. It is the nurse's duty to guide the patient and family about the treatment and relevant questions, conveying tranquility and security. Humanized assistance is necessary, as well as a commitment of the team towards patients and families, effective listening and communication are essential in welcoming the person.Descriptors: Mental Health, Schizophrenia, Care, Nursing. El papel de la enfermera en la asistencia a las personas esquizofrénicasResumen: La teoría genética considera que la esquizofrenia es un trastorno hereditario y también puede estar asociada con factores ambientales como el consumo de drogas, el tabaquismo y las enfermedades autoinmunes. Los trastornos de la conciencia, el comportamiento, la percepción, las emociones y el pensamiento son signos y síntomas que representan los trastornos mentales. Comprender el papel de las enfermeras en la asistencia a las personas esquizofrénicas. Investigación de revisión descriptiva e investigativa, se utilizaron artículos publicados en portugués e inglés, en los años 2011 a 2019, teniendo como fuente las bases de datos: LILACS, BDNEF, MEDLINE, INDEXPSI, SCIELO y ABRASME. El enfoque de los enfermeros que trabajan en salud mental debe ser promover la salud de las personas con trastornos y sus familias, para una mejor calidad de vida del paciente y la prevención de lesiones, de manera holística, integral y humanizada. Es deber del enfermero orientar al paciente y familiares sobre el tratamiento y las preguntas relevantes, transmitiéndole tranquilidad y seguridad. La asistencia humanizada es necesaria, así como el compromiso del equipo con los pacientes y sus familias, la escucha y la comunicación efectivas son fundamentales en la acogida de la persona.Descriptores: Salud Mental, Esquizofrenia, Cuidados, Enfermería.

Inferred Clades of Transposable Elements in Drosophila Suggest Co-evolution with piRNAs

Transposable elements (TEs) are self-replicating “genetic parasites” ubiquitous to eukaryotic genomes. In addition to conflict between TEs and their host genomes, TEs of the same family are in competition with each other. They compete for the same genomic niches while experiencing the same regime of copy-number selection. This suggests that competition among TEs may favor the emergence of new variants that can outcompete their brethren. To investigate the sequence evolution of TEs, we developed a method to infer clades: collections of TEs that share SNP variants and represent distinct TE family lineages. We applied this method to a panel of 85 Drosophila melanogaster genomes and found that the genetic variation of several TE families shows significant population structure that arises from the population-specific expansions of single clades. We used population genetic theory to classify these clades into younger versus older clades and found that younger clades are associated with a greater abundance of sense and antisense piRNAs per copy than older ones. Further, we find that the abundance of younger, but not older clades, is positively correlated with antisense piRNA production, suggesting a general pattern where hosts preferentially produce antisense piRNAs from recently active TE variants. Together these findings suggest a co-evolution of TEs and hosts, where new TE variants arise by mutation, then increase in copy number, and the host then responds by producing antisense piRNAs which may be used to silence these emerging variants.

The quantitative genetics of the endemic prevalence of infectious diseases: Indirect Genetic Effects dominate heritable variation and response to selection

Pathogens have profound effects on life on earth, both in nature and agriculture. Despite the availability of well-established epidemiological theory, however, a quantitative genetic theory of the host population for the endemic prevalence of infectious diseases is almost entirely lacking. While several studies have demonstrated the relevance of the transmission dynamics of infectious diseases for heritable variation and response to selection of the host population, our current theoretical framework of quantitative genetics does not include these dynamics. As a consequence, we do not know which genetic effects of the host population determine the prevalence of an infectious disease, and have no concepts of breeding value and heritable variation for endemic prevalence.Here we propose a quantitative genetic theory for the endemic prevalence of infectious diseases. We first identify the genetic factors that determine the prevalence of an infectious disease, using an approach founded in epidemiological theory. Subsequently we investigate the population level effects of individual genetic variation on R0 and on the endemic prevalence. Next, we present expressions for the breeding value and heritable variation, for both prevalence and individual binary disease status, and show how these parameters depend on the endemic prevalence. Results show that heritable variation for endemic prevalence is substantially greater than currently believed, and increases when prevalence approaches zero, while heritability of individual disease status goes to zero. We show that response of prevalence to selection accelerates considerably when prevalence goes down, in contrast to predictions based on classical genetic models. Finally, we show that most of the heritable variation in the endemic prevalence of the infection is due to indirect genetic effects, suggestion a key role for kin-group selection both in the evolutionary history of current populations and for genetic improvement strategies in animals and plants.

The Cancer Genome: Paradigm or Paradox?

Nowadays, many professionals are sequencing the DNA and studying the cancer genome. However, if the genetic theory of cancer is flawed, our faith in the cancer genome will falter. If gene sequencing is only a tool, we should question what we are making or creating with this tool. When we do not have the right cancer theory at our disposal, we cannot be sure that what we create from the cancer genome is meaningful or useful. In this article, we illustrate that mosaicism, CHIP, and heteroplasmy dispute our traditional perspectives about a genetic origin of cancer and challenge our current narratives about the cancer genome. We caution that when we have the wrong cancer theory, big data can provide poor evidence. Precision medicine may become rather imprecise. Targeted therapy either does not work or work for the wrong reasons. The cancer genome thus becomes a paradox rather than a paradigm.

LENGUAJE, FORMA INTERNA Y EXISTENCIA: LA FILOSOFÍA DEL LENGUAJE DE ANTON MARTY

El artículo analiza ciertos temas centrales de la filosofía del lenguaje de Anton Marty: primero, su teoría genética del origen casual del lenguaje; segundo, su descripción de los componentes mereológicos y semánticos del lenguaje, en particular del concepto de forma inter-na; tercero, su crítica del juicio categórico, basada en sus análisis de las oraciones impersonales y existenciales; cuarto, la importancia del concepto de existencia para aclarar problemas ontológicos. El trabajo hace además hincapié en señalar las conexiones entre su pensamiento y el de Edmund Husserl, ambos discípulos de Franz Brentano.The article addresses some essential issues of Anton Marty’s philosophy of language: first, its genetic theory of the random origin of language; second, his description of the mereological and the semantic components of language, focused on the concept of internal form; third, its criticism of the categorical judgment, based on its analyses of impersonal and existential sentences; fourth, the importance of the concept of existence in order shed light upon ontological problems. The paper also focuses on emphasizing the connections between his thought and that of Edmund Husserl, both disciples of Franz Brentano.