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D4 Dopamine receptor genes of zebrafish and effects of the antipsychotic clozapine on larval swimming behaviour.

Zebrafish, a model developmental genetic organism, is being increasingly used in behavioural studies. We have initiated studies designed to evaluate the response of zebrafish to antipsychotic drugs. This study focuses on characterization of zebrafish D4 dopamine receptors (D4Rs) and the response of larval zebrafish to the atypical antipsychotic clozapine. The D4R is of interest because of its high affinity for clozapine, while interest in clozapine stems from its effectiveness in reducing symptoms in acutely psychotic, treatment-resistant schizophrenic patients. By mining the zebrafish genomic database, we identified three distinct D4R genes, drd4a, drd4b and drd4c, and generated full-length open reading frames encoding each of the three D4Rs by reverse transcription-polymerase chain reaction. Gene mapping studies showed that each D4R gene mapped to a distinct chromosomal location in the zebrafish genome, and each gene exhibited a unique expression profile during embryogenesis. When administered to larval zebrafish, clozapine produced a rapid and profound effect on locomotor activity. The effect of clozapine was dose-dependent, resulted in hypoactivity and was prevented by the D4-selective agonist ABT-724. Our data suggest that the inhibitory effect of clozapine on the locomotor activity of larval zebrafish may be mediated through D4Rs.

Amino Acid Sequence↗

Genetic epidemiological study of schizophrenia: reproduction behaviour.

Data from the Tomsk Epidemiological Register and epidemiological family sample were used to study the relationship between schizophrenics' reproductive behaviour (marital status and fertility rate), severity of ICD-9 schizophrenia and risk of illness among relatives of probands. The results are interpreted in terms of multifactorial threshold and single monolocus models. Their importance for the interpretation of epidemiological data (a change of prevalence rate, cohort effect and clinical polymorphism) is discussed.

Adult↗

Mobile genetic elements in Drosophila melanogaster (recent experiments).

Recent data obtained in the authors' laboratories concerning the behaviour of mobile genetic elements of Drosophila melanogaster are reviewed. It was found that the mobile element jockey represents the typical LINE element. It is efficiently transcribed in D. melanogaster cells in flies and in culture. Transcription is initiated from the +1 nucleotide of jockey and depends on an internal promoter. This is the first case of an internal promoter being used by RNA polymerase II. Several events which take place during the transposition bursts in ctMR2 family of strains were described. Among them are the removal of mobile dispersed genetics (mdg) elements (with solo long terminal repeat (LTR) remaining at the site of excision), complete removal of an mdg element, and reinsertion of the same mdg to the same place either in the presence or in absence of solo LTR sequence. Finally, the formation of deletions was observed. A 462-bp deletion destroying the white locus can be further repaired (w+ reversion). Thus, transposition bursts include many different genetic events. A novel system of prolonged genome destabilization was described. It depends on mobilization of a new mobile element called Stalker. After certain crosses Stalker actively moves for dozens of generations giving rise to large numbers of insertion mutations. Several novel genes were detected using mobilized Stalker. They include a modifier of mdg4 and six enhancers of yellow mutations.

Animals↗

Genetic and environmental contributions to pro-social attitudes: a twin study of social responsibility.

Although 51 twin and adoption studies have been performed on the genetic architecture of antisocial behaviour, only four previous studies have examined a genetic contribution to pro-social behaviour. Earlier work by the author with the University of London Institute of Psychiatry Adult Twin Register found that genes contributed approximately half of the variance to measures of self-report altruism, empathy, nurturance and aggression, including acts of violence. The present study extends those results by using a 22-item Social Responsibility Questionnaire with 174 pairs of monozygotic twins and 148 pairs of dizygotic twins. Forty-two per cent of the reliable variance was due to the twins' genes, 23% to the twins' common environment and the remainder to the twins' non-shared environment.

Adult↗

[Behaviour phenotypes].

INTRODUCTION: In the same way as the genetic basis of disease and developmental disorders with behavioural and intellectual features are being discovered, the opportunity of studying how genes may affect conduct is also developing in both dysfunctional and normal situations. DEVELOPMENT: The most useful models for studying this problem are the genetic disorders in which the genetic defect has been discovered or is being traced. In parallel with advances in genetics, the behaviour patterns found in each disorder are also being defined and are known as behaviour phenotypes. CONCLUSIONS: In this article we aim to illustrate information currently available in the field of behaviour phenotypes. The behaviour and intellectual characteristics of the following syndromes are therefore described: fragile X, premutation of the fragile X syndrome, velocardiofacial, Prader Willi, Rett, Angelman and Williams.

Angelman Syndrome↗

Genetic epidemiology of binging and vomiting.

BACKGROUND: Bulimia nervosa is typically defined as the combination of the behaviours of binging and vomiting. We sought to clarify the relationship of these behaviours from a genetic epidemiological perspective. METHOD: Using data on the lifetime history of binging and vomiting from a personally interviewed population-based sample of female twins (n = 1897), we applied bivariate twin modelling to estimate the sources of variation for these traits. RESULTS: The association between having ever binged (23.6%) and having ever induced vomiting (4.8%) was very strong (odds ratio = 8.78, P << 0.0001). The best-fitting model indicated that lifetime binging and vomiting were both heritable (46% and 72%) and influenced by individual-specific environmental factors (54% and 28%). The overlap between the genetic (ra = 0.74) and individual-specific environmental factors (re = 0.48) for the two traits was substantial. No violations of the equal environmental assumption were evident. CONCLUSIONS: Including binging and vomiting under the rubric of bulimia nervosa appears to be appropriate. Our data are consistent with the identification of binging and vomiting as complex traits resulting from the interplay of multiple genes and individual-specific environmental influences. In contrast to 'environmentalist' theories, our results suggest that genetic influences may be of particular relevance to the aetiology of binging and vomiting.

Adult↗

Molecular ecology of social behaviour: analyses of breeding systems and genetic structure.

Molecular genetic studies of group kin composition and local genetic structure in social organisms are becoming increasingly common. A conceptual and mathematical framework that links attributes of the breeding system to group composition and genetic structure is presented here, and recent empirical studies are reviewed in the context of this framework. Breeding system properties, including the number of breeders in a social group, their genetic relatedness, and skew in their parentage, determine group composition and the distribution of genetic variation within and between social units. This group genetic structure in turn influences the opportunities for conflict and cooperation to evolve within groups and for selection to occur among groups or clusters of groups. Thus, molecular studies of social groups provide the starting point for analyses of the selective forces involved in social evolution, as well as for analyses of other fundamental evolutionary problems related to sex allocation, reproductive skew, life history evolution, and the nature of selection in hierarchically structured populations. The framework presented here provides a standard system for interpreting and integrating genetic and natural history data from social organisms for application to a broad range of evolutionary questions.

Animals↗

[The role of leptin in human obesity].

The mechanism involved in body mass regulation in humans includes genetic, environmental, and behavioural factors. Human obesity is usually associated with a positive energy balance. Genetic studies in obese mice have revealed the Ob. gene, its products leptin and the leptin receptor to be important factors in the regulation of both appetite and energy expenditure. Leptin is a 16-kilodaltons adipocyte-derived hormone -which circulates in the serum as the free and bound forms. The leptin serum level reflects the amount of energy stored in adipose tissue. Leptin acts through the leptin receptor, -which belongs to the cytokine - receptor family. In rodents as well as in humans, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia, and reduced energy expenditure. Recent studies have demonstrated that Ob. gene expression is increased in human obesity. However, mutations of Ob. gene present in the mouse are rare in the human population.

Animals↗

Of mice and kin: the functional significance of kin bias in social behaviour.

1. Sharing recent ancestry (kinship) increases the degree of genetic similarity between individuals, where genetic similarity could mean anything from sharing a particular allele to sharing an entire genome. 2. Genetic similarity can influence behavioural and other responses between individuals in a number of ways, discriminatory and non-discriminatory. All are likely to result in kin bias, because of the correlation between genetic similarity and kinship, but only some should be regarded as involving kin discrimination. 3. Non-discriminatory kin bias could arise through close relatives sharing, for instance, physical characteristics (such as those influencing competitive ability), thresholds of behavioural response or requirements for particular resources. 4. Discriminatory kin bias could arise through the direct perception of genetic similarity between individuals (direct similarity discrimination) or the use of cues likely to correlate with genetic similarity (indirect similarity discrimination--of which kin discrimination is one form). Alternatively, it could arise incidentally through mistaken identity or discrimination at some other level, such as species identification. 5. Experiments with laboratory and wild house mice have revealed kin bias in a number of contexts, including (a) parental and infanticidal behaviour, (b) sexual development and behaviour and (c) investigatory behaviour and passive body contact among juveniles and adults. 6. While kin bias in mice has been interpreted as evidence for kin discrimination, there are several problems with such an interpretation. These include (a) pronounced and complex effects of familiarity on discrimination, (b) a high risk of error-proneness in the indirect cues used in apparent kin discrimination and (c) weak and easily disrupted kin bias effects in certain contexts. 7. Consideration of social structure and discriminatory responses within populations of wild house mice leads to an alternative explanation for some kin bias in terms of incidental discrimination based on social group membership. 8. Several results from laboratory experiments suggest incidental discrimination is a more parsimonious explanation than kin discrimination for some intrasexual kin bias in behaviour. However, kin or direct similarity discrimination appears to be the most likely explanation for other aspects of intrasexual kin bias and for intersexual kin bias.

Animals↗

Integrative animal behaviour and sociogenomics.

Integrative animal behaviour is on the rise: some behavioural neuroscientists are increasingly asking 'why', while some behavioural ecologists are starting to ask 'how'. For example, the most recent edition of Krebs and Davies' authoritative Behavioural Ecology: an Evolutionary Approach contains, for the first time, a section on mechanistic analyses of behaviour within an ecological context. This nascent synthesis can be catalysed by molecular genetic analyses of behaviours that occur in a natural context. Recent findings can provide a foundation for increased integration in the study of social behaviour, and provide the basis for an agenda for research on 'sociogenomics'.

Journal Article↗

Generalisation of conditioned fear and its behavioural expression in mice.

Mice are favourite subjects in molecular and genetic memory research and frequently studied with classical fear conditioning paradigms that use an auditory cue (conditioned stimulus, CS(+)) to predict an aversive, unconditioned stimulus (US). Yet the conditions that control fear memory specificity and generalisation and their behavioural expression in such conditioned mice have not been analysed systematically. In the current study we addressed these issues in the most widely used mouse strain of behavioural genetics, C57Bl/6. In keeping with findings in other species we demonstrate the dependence of fear memory generalisation on training intensity (i.e. both US intensity and the number of CS(+) and US applied) after both excitatory (explicitly paired presentation of CS(+) and US) and inhibitory training (explicitly unpaired presentation of CS(+) and US). Furthermore, inhibitory overtraining was associated with changes of uncued anxiety-like behaviour in a light/dark exploration test, indicative of an emotional sensitisation reaction as consequence of a lack of US predictability. Together our results describe the qualitatively and quantitatively different increases of defensive behaviour in response to conditioned stimuli of different salience and identify training conditions that lead to fear memory generalisation and emotional sensitisation in C57Bl/6 inbred mice.

Acoustic Stimulation↗

Molecular evolution and quantitative variation for chemosensory behaviour in the nematode genus Caenorhabditis.

Caenorhabditis elegans is a model organism in biology, yet despite the tremendous information generated from genetic, genomic and functional analyses, C. elegans has rarely been used to address questions in ecological genetics. Here, we analyse genetic variation for chemosensory behaviour, an ecologically important trait that is also genetically well characterized, at both the phenotypic and molecular levels within three species of the genus Caenorhabditis. We show that the G-protein ODR-3 plays an important role in chemosensory avoidance behaviour and identify orthologues of odr-3 in C. briggsae and C. remanei. Both quantitative genetic analysis of chemosensory behaviour and molecular population genetic analysis of odr-3 show that there is little genetic variation among a worldwide collection of isolates of the primarily selfing C. elegans, whereas there is substantially more variation within a single population of the outcrossing C. remanei. Although there are a large number of substitutions at silent sites within odr-3 among the three species, molecular evolution at the protein level is extremely conserved, suggesting that odr-3 plays an important role in cell signalling during chemosensation and/or neuronal cilia development in C. remanei and in C. briggsae as it does in C. elegans. Our results suggest that C. remanei may be a more suitable subject for ecological and evolutionary genetic studies than C. elegans.

Animals↗

Not in their genes: phenotypic flexibility, behavioural traditions and cultural evolution in wild bonnet macaques.

Phenotypic flexibility, or the within-genotype, context-dependent, variation in behaviour expressed by single reproductively mature individuals during their lifetimes, often impart a selective advantage to organisms and profoundly influence their survival and reproduction. Another phenomenon apparently not under direct genetic control is behavioural inheritance whereby higher animals are able to acquire information from the behaviour of others by social learning, and, through their own modified behaviour, transmit such information between individuals and across generations. Behavioural information transfer of this nature thus represents another form of inheritance that operates in many animals in tandem with the more basic genetic system. This paper examines the impact that phenotypic flexibility, behavioural inheritance and socially transmitted cultural traditions may have in shaping the structure and dynamics of a primate society--that of the bonnet macaque (Macaca radiata), a primate species endemic to peninsular India. Three principal issues are considered: the role of phenotypic flexibility in shaping social behaviour, the occurrence of individual behavioural traits leading to the establishment of social traditions, and the appearance of cultural evolution amidst such social traditions. Although more prolonged observations are required, these initial findings suggest that phenotypic plasticity, behavioural inheritance and cultural traditions may be much more widespread among primates than have previously been assumed but may have escaped attention due to a preoccupation with genetic inheritance in zoological thinking.

Animals↗

Heritability and fitness-related consequences of squid personality traits.

Dumpling squid, Euprymna tasmanica, show consistent individual differences in behaviour that can be classified according to indices reflecting shy-bold, activity and reactivity responses. Using crosses of wild-caught single males to multiple females with known behavioural phenotypes, this study estimated patterns of additive genetic and residual variance in these behavioural traits from offspring of squid in two contexts, a threat (antipredator) and feeding (foraging) test. Genetic contributions to behavioural expression were dependent on test context. Behaviours in antipredator contexts had significant heritabilities (h(2) = 0.2-0.8) while behaviours from foraging contexts had lesser additive genetic and greater residual components (h(2) = 0.05-0.08). Personality trait variation in females was not related to her fecundity. Female boldness in foraging situations, which co-varied with body size, explained small but significant variation ( approximately 21%) in brood hatching success, while successful fertilization was determined by positive assortion of mate pairs according to their shy-bold phenotype. These results are discussed in terms of the ecological and evolutionary significance of animal "personality" traits in wild populations of animals.

Animals↗

A twin study of anxiety-related behaviours in pre-school children.

BACKGROUND: From middle childhood onwards, substantial evidence points to phenotypic differentiation between anxiety diagnostic categories such as generalised anxiety, separation anxiety, specific phobia, and obsessive-compulsive disorders. However, little is known about the genetics of these categories and especially about the phenotypic and genetic structure of related behaviours in pre-school children. METHODS: We examined the phenotypic differentiation and genetics of mother-reported anxiety-related behaviours in 4,564 four-year-old twin pairs, from a population-based sample. RESULTS: Confirmatory factor analyses provided support for five correlated factors: General Distress, Separation Anxiety, Fears, Obsessive-Compulsive Behaviours, and Shyness/Inhibition. Genetic influences were found on all five factors, but the pattern of influences differed considerably across them, with particularly high heritability estimates for Obsessive-Compulsive Behaviours and Shyness/Inhibition, and substantial shared environmental influence on Separation Anxiety. Multivariate genetic analyses revealed moderate genetic correlations between the five factors. Genetic overlap was particularly pronounced between General Distress and the other anxiety-related behaviours, accounting for about half of their covariance. Genetic variance on Obsessive-Compulsive Behaviours was the least correlated with the other scales. The shared environmental influences correlated highly across the factors, accounting for the greatest proportion of covariation between Separation Anxiety, Fears and Obsessive-Compulsive Behaviours. The non-shared environment influences were largely variable specific. CONCLUSIONS: These data provide evidence for phenotypic and genetic overlap as well as differentiation between aspects of anxiety-related behaviours in young children. We conclude that research with young children will benefit from more specific assessments of anxiety-related behaviours in addition to less differentiated assessments of 'internalising' symptoms.

Anxiety Disorders↗