Genetics has been an important tool for discovering new aspects of biology across life. In humans, there is growing momentum behind the application of this knowledge to drive innovation in clinical care, most notably through developments in precision medicine. Nowhere has the impact of genetics on clinical practice been more striking than in the field of rare disorders. For most of these conditions, individual disease susceptibility is influenced by DNA sequence variation in a single or a small number of genes. In contrast, most common disorders are multifactorial and are caused by a complex interplay of multiple genetic, environmental and stochastic factors. The longstanding division of human disease genetics into rare and common components has obscured the continuum of human traits and echoes aspects of the century-old debate between the Mendelian and biometric views of human genetics. In this article, we discuss the differences in data and concepts between rare and common disease genetics. Opportunities to unify these two areas are noted and the importance of adopting a holistic perspective that integrates diverse genetic and environmental factors is discussed.

Attention-deficit/hyperactivity disorder (ADHD) and obesity are positively associated, with increasing evidence that they share genetic risk factors. Our aim was to examine whether these findings apply to both types of ADHD symptoms for female and male adolescents. We used data from 791 girl and 735 boy twins ages 16−17 years to examine sex-specific phenotypic correlations between the presence of ADHD symptoms and overweight/obese status. For correlations exceeding .20, we then fit bivariate twin models to estimate the genetic and environmental correlations between the presence of ADHD symptoms and overweight/obese status. ADHD symptoms and height/weight were parent- and self-reported, respectively. Phenotypic correlations were .30 (girls) and .08 (boys) for inattention and overweight/obese status and .23 (girls) and .14 (boys) for hyperactivity/impulsivity and overweight/obese status. In girls, both types of ADHD symptoms and overweight/obese status were highly heritable, with unique environmental effects comprising the remaining variance. Furthermore, shared genetic effects explained most of the phenotypic correlations in girls. Results suggest that the positive association of both types of ADHD symptoms with obesity may be stronger in girls than boys. Further, in girls, these associations may stem primarily from shared genetic factors.

Attitudes to animal biotechnology are diverse, partly because people have different viewpoints and often do not recognize or acknowledge this to be so. First, people adopt different ethical approaches. If an opponent of genetic manipulation says’ I don't like the idea of altering animals ‘biology’ and a proponent replies’… but it is useful’, they are failing to communicate, because one is asking whether the action is right or wrong, whereas the other emphasizes the consequences. Another approach focuses on the person carrying out the action. Many people have hybrid views combining elements of these different approaches. Second, people ‘s concepts of welfare vary, emphasizing animal minds, bodies or natures - or a combination of these. A proponent who argues that a particular genetic change will not cause suffering is unlikely to reassure an opponent who puts more emphasis on naturalness than on feelings or health. An improved dialogue, in which people attempt to understand one another's viewpoints, may enable common principles to be established and practical measures to be taken that enable more cooperation in attempts to improve both human and animal welfare.

In this paper we describe the existence and consequences of subspecific and individual variation in the genetic make-up of house mice. The purpose is to illustrate forms of variation that are often neglected in discussions about animal care and experimental design. Towards this end, different inbred mouse strains as well as genetically selected mouse lines are compared in relation to their ecological origin. Firstly, the behaviour of BALB/c, C57BL/6J and CBA mice is described in relation to different habitats. Furthermore, their aggression is compared, as measured by two paradigms. It appears that some inbred lines (eg BALB/c and C57BL/6J) clearly show behaviour that reflects the functional adaptation to the natural habitats in which their ancestors lived. Other strains (eg CBA) show a lack of such behavioural adaptation and their phenotypes appear to be very unstable over time. Secondly, two fundamentally different characters, both present in populations of wild house mice and under genetic control, are described: on the one hand, active copers are characterized by aggressive behaviour; on the other hand, passive copers are reluctant to attack. The active, aggressive animals (manipulators) are well adapted to an invariant environment like their own territory, whereas the passive, non-aggressive copers (adjustors) are well adapted to a changing environment, eg when roaming. We discuss to what extent these coping styles are present in laboratory strains of mice. The major conclusion with regard to both phenomena is that individual and subspecific variation may have significant implications for experimental design and the welfare of the experimental animals.

This paper reviews the history of the establishment of dog breeds, summarizes current health and resultant welfare problems and makes some positive suggestions for their resolution. Some breed standards and selection practices run counter to the welfare interests of dogs, to the extent that some breeds are characterized by traits that may be difficult to defend on welfare grounds. Meanwhile, little selection pressure seems to be exerted on some traits that would improve animal welfare and produce dogs better suited to modern society. Unfortunately, the incidence of certain inherited defects in some breeds is unacceptably high, while the number of registered animals of certain breeds within some countries is so low as to make it almost impossible for breeders to avoid mating close relatives. There are several constructive ways to overcome these challenges. Breed associations can ensure that reduction of welfare problems is one of their major aims; they can review breed standards; they can embrace modern technology for animal identification and pedigree checking; they can allow the introduction of ‘new ‘ genetic material into closed stud-books; and they can encourage collaboration with geneticists in identifying and using DNA markers for the control of inherited disorders. There should be a concerted effort to produce and evaluate as companion animals first-cross (F1) hybrids from matings between various pairs of breeds. Finally, geneticists must learn to communicate their science better and in a language that non-geneticists can understand.

Cardiovascular diseases (CVDs) are complex in their aetiology, arising due to a combination of genetics, lifestyle and environmental factors. By nature of this complexity, different CVDs vary in their molecular mechanisms, clinical presentation and progression. Although extensive efforts are being made to develop novel therapeutics for CVDs, genetic heterogeneity is often overlooked in the development process. By considering molecular mechanisms at an individual and ancestral level, a richer understanding of the influence of environmental and lifestyle factors can be gained and more refined therapeutic interventions can be developed. It is therefore expedient to understand the molecular and clinical heterogeneity in CVDs that exists across different populations. In this review, we highlight how the mechanisms underlying CVDs vary across diverse population ancestry groups due to genetic heterogeneity. We then discuss how such genetic heterogeneity is being leveraged to inform therapeutic interventions and personalised medicine, highlighting examples across the CVD spectrum. Finally, we present an overview of how polygenic risk scores and Mendelian randomisation can foster more robust insight into disease mechanisms and therapeutic intervention in diverse populations. Fulfilment of the vision of precision medicine requires more exhaustive leveraging of the genetic variability across diverse ancestry populations to improve our understanding of disease onset, progression and response to therapeutic intervention.

Farm assurance schemes can set standards to assure compliance with specific requirements relating to animal welfare. As such, standards can be set to address genetic-related welfare problems in farm animals, such as those associated with fast growth rates in meat chickens (broilers) (Gallus gallus domesticus). Based on discussions with broiler breeding companies, broiler producers and in line with published research, the RSPCA placed a maximum limit on the genetic growth rate potential of broilers that could be used within its own farm assurance scheme — Freedom Food. Despite the introduction of this requirement, the number of birds reared on the scheme increased from 25 million to 55 million per year over a three-year period, with all of these birds meeting the genetically slower growing requirement. In addition, the two largest global broiler breeding companies responded to this change in the market by each developing a genetically slower growing bird. This demonstrates that assurance schemes can have a pivotal role in tackling genetic welfare problems in farm animals, such as those associated with fast growth in broilers.

In farm animal breeding, behavioural traits are rarely included in selection programmes despite their potential to improve animal production and welfare. Breeding goals have been broadened beyond production traits in most farm animal species to include health and functional traits, and opportunities exist to increase the inclusion of behaviour in breeding indices. On a technical level, breeding for behaviour presents a number of particular challenges compared to physical traits. It is much more difficult and time-consuming to directly measure behaviour in a consistent and reliable manner in order to evaluate the large numbers of animals necessary for a breeding programme. For this reason, the development and validation of proxy measures of key behavioural traits is often required. Despite these difficulties, behavioural traits have been introduced by certain breeders. For example, ease of handling is now included in some beef cattle breeding programmes. While breeding for behaviour is potentially beneficial, ethical concerns have been raised. Since animals are adapted to the environment rather than the other way around, there may be a loss of ‘naturalness’ and/or animal integrity. Some examples, such as breeding for good maternal behaviour, could enhance welfare, production and naturalness, although dilemmas emerge where improved welfare could result from breeding away from natural behaviour. Selection against certain behaviours may carry a risk of creating animals which are generally unreactive (‘zombies’), although such broad effects could be measured and controlled. Finally, breeding against behavioural measures of welfare could inadvertently result in resilient animals (‘stoics’) that do not show behavioural signs of low welfare yet may still be suffering. To prevent this, other measures of the underlying problem should be used, although cases where this is not possible remain troubling.

This study investigates the genetic basis of lamb vigour (defined as neonatal lamb activity and sucking ability) and lambing difficulty as potential traits to be included in selection programmes to improve ewe and lamb welfare. Scores for lamb birth difficulty, vigour and sucking ability were collected shortly after birth on 1,520 lambs born in 2006 in 19 different flocks that were members of the UK Suffolk Sire Referencing Scheme. Scores evaluated each trait on a scale of 1 to 4; 1 being no assistance given either during birth or to suck, or excellent vigour, through to 4 where a large degree of assistance was required, or poor vigour. Genetic parameters (heritabilities, genetic correlations) were estimated by fitting an individual animal model using ASREML. Variance components obtained from univariate and bivariate analyses were averaged to provide genetic parameter estimates. Heritabilities for birth difficulty and vigour were moderate but heritability for sucking ability was not significant. The genetic correlation between vigour and sucking ability was positive and high, that between vigour and birth difficulty moderately negative, and that between birth difficulty and sucking ability not significant. Birth difficulty and vigour could be included in Suffolk breeding programmes to help reduce health and welfare problems associated with these traits in Suffolk sheep, and in flocks producing crossbred lambs sired by Suffolk rams. Further work is required to evaluate correlations between these traits and performance traits and to comprehensively validate the scoring system once more data become available.

The 150th anniversary of the publication of The Origin of Species… is a good time to consider how selection can affect welfare — the quality of life. Darwin (1859) quoted Youatt's description of selective breeding: “…the magician's wand, by means of which he may summon into life whatever form and mould he pleases”. Evolution has fairly recently included us humans in its toolbox, alongside its older instruments, such as climate and disease, as significant agents of selection. We have taken to this work vigorously and have summoned into life an extraordinary array of creatures. It is only much more recently, with the development of interest in animal welfare science, that the welfare consequences of this have begun to be critically reviewed. There are two ways that selection can affect welfare: (i) by resulting in changes that make aversive feelings more likely, eg by predisposing to disease or by altering behaviour such as to increase risk of disease or injury, and (ii) by altering sensitivity of the affect systems such that animals feel, for example, more (or less) pain or fear in response to a stimulus than their ancestors would have. Comparing natural and human selection — that is, the simultaneous scrutiny of all aspects of biology as opposed to our selection for one or two features that appeal to us — Darwin (1859) wrote: “Can we wonder, then, that nature's productions should be far ‘truer’ in character than man's productions; that they should be infinitely better adapted to the most complex conditions of life, and should plainly bear the stamp of far higher workmanship”. The aims of this meeting were to discuss how selection can affect welfare and how we can improve our workmanship in the interests of animal welfare.

Merino ewes have been selected, over 18 generations, for calm (C) or nervous (N) temperament using using an arena test and an isolation box test. We investigated the relative contributions of genotype versus the post-partum behaviour of the dam on the temperament of the lambs using a cross-fostering procedure. Forty-eight multiparous calm and 52 nervous ewes were artificially inseminated with the semen of a sire of the same temperament. At birth, 32 lambs of a given temperament line were cross fostered to ewes from the other line (16 N × C, 16 C × N), 34 lambs were cross fostered to ewes from the same line (15 C × C, 19 N × N) and 30 lambs were left with their birth mother (15 C, 15 N), to control for the effect of cross fostering. The temperament of the progeny was assessed at two occasions, one week after birth by measuring locomotor activity during an open-field test and at weaning (16 weeks) by measuring locomotor activity during an arena test and agitation score measured during an isolation box test. There was a genotype effect but no maternal or fostering effect on the lamb temperament at one week. This may be because the maternal behaviour of the foster ewes did not differ considerably between the calm and nervous mothers during adoption or within the first week, post partum. Similarly, at weaning, only a genotype effect was found on the locomotor and agitation score. Therefore, it appears that temperament in Merino sheep is mainly determined by the genetic transmission of the trait across generations rather than behaviours learned from the mother.

Genetics is key to the improvement of welfare in broiler chickens at both juvenile and adult (breeder) stages but progress is hampered currently by the seemingly conflicting demands of welfare, commercial production, food security and calls for increasing intensification to curb climate change. Animal welfare is therefore most likely to be improved on a commercial scale by future breeding programmes that incorporate multiple goals of different stakeholders as far as possible and give higher priority to animal welfare. These include: i) broilers with high welfare traits; ii) broiler breeders that do not need feed restriction; iii) birds that can be grown in an economically profitable way; iv) birds with low disease levels without the need for routine medication; v) chicken meat that is healthy and good for humans to eat; and (vi) broilers and breeders that thrive in systems that are environmentally sustainable. Progress towards achieving these goals is hampered currently by the assumptions that high juvenile growth rate is incompatible with good welfare and that feed restriction in adults is inevitable with fast-growing juveniles. We challenge these assumptions at both genetic and whole-animal level and argue that the conflict between good welfare and productivity can be reduced by making use of all available genetic variation from existing breeds and other sources and selecting birds in the range of environments they will encounter in commercial production.

Mitochondria play a key role in cell homeostasis as a major source of intracellular energy (adenosine triphosphate), and as metabolic hubs regulating many canonical cell processes. Mitochondrial dysfunction has been widely documented in many common diseases, and genetic studies point towards a causal role in the pathogenesis of specific late-onset disorder. Together this makes targeting mitochondrial genes an attractive strategy for precision medicine. However, the genetics of mitochondrial biogenesis is complex, with over 1,100 candidate genes found in two different genomes: the nuclear DNA and mitochondrial DNA (mtDNA). Here, we review the current evidence associating mitochondrial genetic variants with distinct clinical phenotypes, with some having clear therapeutic implications. The strongest evidence has emerged through the investigation of rare inherited mitochondrial disorders, but genome-wide association studies also implicate mtDNA variants in the risk of developing common diseases, opening to door for the incorporation of mitochondrial genetic variant analysis in population disease risk stratification.

We investigate differences in profitability of three Aberdeen-influenced breeds, Angus, Red Angus, and American Aberdeen. Using data from North Dakota, we measure differences in birth weights, calving intervals, weaning weights, cow weights, and profitability. Weaning weights differ between breeds, setting up a trade-off between lower feed costs for smaller cows and higher revenue for larger cows. American Aberdeen-influenced cows bred to Red Angus bulls have $1–$6 per acre higher returns than Angus or Red Angus-influenced cows. Aberdeen sires have the lowest returning calves.

Children with callous–unemotional (CU) traits are at risk for severe conduct problems. While CU traits are moderately heritable, parenting also predicts risk. However, few studies have investigated whether parenting factors (e.g., acceptance, conflict, parental psychopathology) moderate the etiology of CU traits, while accounting for gene–environment correlations. To address this knowledge gap, we used data from 772 twin pairs from the Adolescent Brain and Cognitive Development Study to test bivariate models that explored overlapping etiological influences on CU traits and child reports of their parenting environment. We also used gene-by-environment interaction models to test whether parenting moderated genetic versus environmental influences. There were no overlapping etiological influences on CU traits and parental acceptance, but modest genetic and non-shared environmental overlap between CU traits and family conflict. Parental acceptance and psychopathology moderated non-shared environmental influences, with stronger non-shared environmental influences on CU traits among children who experienced lower parental acceptance and greater parental psychopathology. Family conflict only moderated environmental influences when models did not covary for conduct problems. Parental acceptance and parental psychopathology may be specific environmental protective and risk factors for CU traits, whereas family conflict may represent a general environmental risk factor for both CU traits and conduct problems.