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Mutations of Drosophila melanogaster that affect muscles.

Eight X-chromosome mutations (falling into five complementation groups) that affect the development and morphology of the indirect flight muscles of Drosophila melanogaster were investigated using histological, behavioural and genetic techniques. All of these mutations result in flightlessness, in a marked reduction in the ability of the flies to jump, and in the wings being held in abnormal positions. Mutations in each of the complementation groups have different effects on the morphology of the muscles. Two (flapwing, vertical wing) result in absence of most of the indirect flight muscle fibres, a third (upheld) is required for the gross organization of muscle structure, another (heldup) is involved in the maintenance of muscle structure once formed, and the fifth seems to be necessary for the detailed architecture of the muscle fibre (indented thorax). The analysis of flies genetically mosaic with respect to each mutation by the technique of fate-mapping suggests that three (heldup, upheld and indented thorax) of the genes concerned have their primary site of action in the musculature itself, while the other two (flapwing and vertical wing) may function primarily in the fat-body and tracheae respectively.

Animals↗

Gastric cancer: epidemiologic and biological aspects.

Although temporal trends and regional-racial variations in gastric cancer incidence have led to the formulation of different hypotheses, no definite association has been seen between this disease and any behavioural or genetic determinant. In fact, several aetiological factors have been associated with risk of gastric cancer, but not without controversy. Various studies have suggested that genetic factors might be of importance in the pathogenesis of gastric tumours. In fact, stomach carcinoma occurs more frequently among close relatives of affected individuals than in the general population and some of the most common pre-cancerous lesions seem to be genetically determined. In the light of this circumstantial evidence, we decided to investigate the role of various genetic alterations in gastric cancer in order to study their relationship with aetiopathogenesis and disease progression and their value as indicators of risk and prognosis. Our main areas of interest were: i. c-Ha-ras locus polymorphism; ii, truncated c-myc gene variant; iii. loss of heterozygosity, iv. p53 gene mutations; v. oncogene amplification; vi. oncogene amplification proliferative activity and their relation to prognosis in gastric cancer.

Carcinoma↗

Genetic and environmental influences on juvenile antisocial behaviour assessed on two occasions.

BACKGROUND: There is conflicting evidence concerning the magnitude of genetic and shared environmental influences on juvenile antisocial behaviour (AB). The use of more than one assessment of AB may yield more accurate estimates of these influences. METHODS: Retrospective reports of antisocial behaviour prior to age 18 were obtained on two occasions from a population-based sample of 3522 adult males from male-male twin pairs: phone interviews (wave 1) and self-report questionnaires obtained 19 months later (wave 2). Structural equation modelling estimated the genetic and environmental influences on reliably-measured AB. Factors related to participation of co-twin at wave 1, attrition between waves 1 and 2, and reliability of wave 1 and wave 2 assessments were also investigated. RESULTS: Twin analyses revealed that genetic, shared environmental, and non-shared environmental influences accounted for approximately 33% (95% CI = 9-57%), 31% (95% CI = 10-51%) and 36% (95% CI = 29-44%) of the variance of reliably measured AB, respectively. We also found significant occasion-specific genetic influences on wave 1 AB. Wave 1 AB did not predict wave 1 participation of co-twin or attrition, but was related to reliability. Co-twins of MZ twins and younger twins were more likely to participate at wave 1; attrition was predicted by being a DZ twin, lack of initial participation of co-twin, fewer years of education, and fewer children. Being older, being unmarried, and having less psychopathology were associated with greater reliability. CONCLUSIONS: When measurement error is taken into account, both genetic and shared environmental factors are significant influences on juvenile AB, accounting for approximately one-third of variation. The origin of the specific genetic influences on wave 1 AB is unclear, but may be due to factors related to measurement.

Adolescent↗

Male-specific fruitless specifies the neural substrates of Drosophila courtship behaviour.

Robust innate behaviours are attractive systems for genetically dissecting how environmental cues are perceived and integrated to generate complex behaviours. During courtship, Drosophila males engage in a series of innate, stereotyped behaviours that are coordinated by specific sensory cues. However, little is known about the specific neural substrates mediating this complex behavioural programme. Genetic, developmental and behavioural studies have shown that the fruitless (fru) gene encodes a set of male-specific transcription factors (FruM) that act to establish the potential for courtship in Drosophila. FruM proteins are expressed in approximately 2% of central nervous system neurons, at least one subset of which coordinates the component behaviours of courtship. Here we have inserted the yeast GAL4 gene into the fru locus by homologous recombination and show that (1) FruM is expressed in subsets of all peripheral sensory systems previously implicated in courtship, (2) inhibition of FruM function in olfactory system components reduces olfactory-dependent changes in courtship behaviour, (3) transient inactivation of all FruM-expressing neurons abolishes courtship behaviour, with no other gross changes in general behaviour, and (4) 'masculinization' of FruM-expressing neurons in females is largely sufficient to confer male courtship behaviour. Together, these data demonstrate that FruM proteins specify the neural substrates of male courtship.

Animals↗

Absence of anxiolytic response to chlordiazepoxide in two common background strains exposed to the elevated plus-maze: importance and implications of behavioural baseline.

Although genetic background is acknowledged as a potentially important determinant of mutant phenotypes, publications on genetically modified mice far outnumber those on progenitor strains. We have recently reported major differences in basal anxiety levels (elevated plus-maze & light/dark exploration) among three strains (C57BL/6JOlaHsd, 129/SvEv and 129S2/SvHsd) employed as progenitor stock in European laboratories (Rodgers et al. in press). Furthermore, the phenotypes of these inbred strains differed significantly from that of an outbred strain (Swiss-Webster) commonly used in behavioural pharmacology. In view of these findings, the present study assessed possible differences in the anxiolytic efficacy of chlordiazepoxide (0, 7.5 & 15.0 mg/kg, IP) in three of these strains (Swiss-Webster (SW), C57BL/6JOIaHsd (C57) & 129S2/SvHsd (129)). Experimentally naive mice were exposed to the elevated plus-maze, sessions were videotaped and behaviour analysed using ethological software. The performance of control subjects confirmed significant strain differences in basal levels of activity (SW > C57 > 129) and anxiety-related behaviours (129 = SW > C57), with hypolocomotion dominating the 129 profile. SW mice displayed an anxioselective response to both doses of chlordiazepoxide (CDP), with significant reductions in open arm avoidance and risk assessment observed in the absence of any change in general activity. In direct contrast, the lower dose of CDP (7.5 mg/kg) was without effect in either inbred strain, whereas treatment with 15.0 mg/kg induced a profile indicative of muscle relaxation/mild sedation in C57 mice and virtually abolished all behavioural activity in 129 mice. Although the absence of an anxiolytic response to CDP in C57 mice may be attributed to their low basal anxiety levels, the profile of 129 mice strongly suggests an abnormality in benzodiazepine/GABAA receptor function. The implications of these findings for research on mutant mice are discussed.

Animals↗

Aggression from a developmental perspective: genes, environments and interactions.

Genetic influences on the social behaviours of non-human mammals are ubiquitous, powerful and readily detected. But demonstrations that social behaviours are influenced by genes constitute only part of the story. Developmental findings have helped complete the picture. Specifically, these studies show that: (1) genetic effects for aggressive behaviours are highly malleable over the course of development; (2) genetic influences on aggressive behaviour are more dynamic, easily achieved and open to rapid manipulation than has been recognized in current models of social evolution and behavioural genetics; (3) developmental timing has a significant impact upon the nature of the genetic effects observed in aggressive behaviours. These empirical results are consistent with the view that social behaviours are among the first features to be influenced by genetic selection and by environmental experience. Social actions have distinctive properties in adaptation because they organize the space between the organism and the environment and promote rapid, selective and novel accommodations. The modern integrative view of the development of individual-in-context brings attention to the correlation between constraints within and external to individuals. This paper reviews findings on how these processes become integrated over time in individuals and species, and their implications for the nurture of nature.

Aggression↗

The behaving brain of a fly.

The use of Drosophila as a suitable system to answer behavioural questions is usually based on the availability of mutant phenotypes. Indeed, the 'single-gene' approach to behaviour was a very illuminating strategy in practical and conceptual terms, and served to prove that the genetic mechanisms sustaining behaviour could be analysed. However, the essence of neurogenetics goes for beyond the utilitarian use of mutants as tools to dissect behavior. Our main contention is that the study of the genetic basis of behaviour requires the study of genomes, rather than single genes, and their functional organization. Here, we use two aspects of behaviour, olfaction and movement control, as examples to illustrate the intricate, albeit understandable, relationship between the genome and behaviour. At present, these examples offer only a glimpse into this relationship. Further progress might be reached if studies on the regulation of functionally related genes are undertaken. On these grounds, it appears that the answer to many fundamental questions about behaviour that are amendable to experimentation might come from the work on Drosophila, providing that the required multidisciplinary efforts are focused on this organism.

Animals↗

Self-injurious behaviour in individuals with intellectual disabilities.

PURPOSE OF REVIEW: In this paper we review literature published in 2004 on self-injurious behaviour in individuals with intellectual disabilities. Reviewed studies examine phenomenology and comorbidity, pharmacological and other interventions, genetic syndromes, and behavioural assessment and treatment. RECENT FINDINGS: Key findings include the possible association between self-injury and impulse control and stereotyped behaviours. Reports on the use of pharmacological interventions provide little evidence for the use such interventions, although the findings of studies on naltrexone seem stronger. In the behavioural phenotype literature the predictors of self-injury in Prader-Willi syndrome are becoming more refined. The behaviour analysis literature reports further development of assessment methodology to cater for idiosyncratic functions and low-rate behaviours. SUMMARY: Developments in the fields of applied behaviour analysis and genetic syndromes highlight the importance of tailored assessments and interventions. Evidence from the pharmacological literature suggests that although significant numbers of individuals are prescribed such interventions, the research evidence for their efficacy is, at best, weak.

Journal Article↗

[Anthropological aspects of behavioural development (author's transl)].

Resulting from psychological, evolutionary and genetical aspects of behavioural development it is attempted go more fully into extent and significance of anthropological researches analysing the conditions of behaviour, particularly by motor development. So the general assertion will be more exact that all anthropological researches applied to structural and functional fundamentals of man are important for analysis of behaviour, its variability, its variability and development too.

Anthropology↗

How heritable is innate behaviour?

The relations between innateness and heritability of behaviour, environmental heterogeneity, genetic diversity of populations, and rates of evolution of behaviour are discussed on the basis of a simple quantitative model. An index I of innateness is proposed which can be related to the heritability index h2. I and h2 are positively related but the degree of correlation depends on the genetic variability of the population, the heterogeneity of the conditioning environment, and the level of spontaneous behavioural variability. The influence of innateness on rates of evolution is moderate. The frequency distributions of I and h2 are unimodal, there is no evidence for an innate-acquired dichotomy.

Animals↗

Life and health insurance behaviour of individuals having undergone a predictive genetic testing programme for hereditary non-polyposis colorectal cancer.

OBJECTIVE AND METHODS: We describe the insurance behaviour of subjects (n=271) who had previously taken a predictive genetic test for hereditary non-polyposis colorectal cancer (HNPCC); 31% of them were mutation positive, indicating a high risk of cancer. One year after testing, subjects were sent a questionnaire including questions about their present life and health insurance before participation in the study, and their actual and planned purchase of the insurance policies during the testing programme which compromised a pre-test counseling session, a period for reflection, the testing, and a test disclosure session. RESULTS: Thirty percent reported that they already had a life insurance and 14% a health insurance before participating in the study. The mutation-positive subjects possessed a health insurance significantly more often than the mutation-negative individuals (21 vs. 11%, p=0.02) and similar trend was observed for life insurance (36 vs. 28%, p=0.12). Life and health insurance policies purchased just before testing was reported by 3 and 2% of the subjects, respectively. Life and health insurance policies purchased after testing were reported by 3 and <1% respectively, and planned purchase by 3 and 2%, respectively. No statistically significant differences were found between the groups defined by mutation status in reports of life or health insurance behaviour during or after the programme. CONCLUSION: According to self-reported data, the mutation-positive subjects did not differ from the others in the purchase of life or health insurance policies. However, the mutation-positive individuals reported that they possessed health insurance policies before entering the study more often than their counterparts.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

[Psychosocial consequences of genetic susceptibility on development of disease].

The development of predictive genetic DNA- tests gives people the choice "to know" or "not to know" a decision with tremendous short-mid- and long-term consequences. Family history of disease can provide information about the increased risk of susceptibility, and these knowledge may have psychosocial implication. The results of studies using genetic testing and their psychological impact are discussed with regard to hereditary cancer (breast, colorectal, prostate) as well as particular neurogenetic disease (e.g. Huntington' disease). Psychological studies on genetic risk concentrating on psychological adjustment, transfer of information within the family and perception of genetic risk in families showed that genetic disease had a considerable impact on family life (e.g. reproductive decisions). Findings showed that people with a family history of cancer (without genetic testing) vary in their illness behaviour, but little is known about the effect of inheredited predisposition to disease (e.g. cancer) on such health related behaviour as smoking, diet, activity level. Genetic information could both increase (strengthening the belief that current behaviour combined with genetic predisposition is putting person at increasing risk of disease) and decrease motivation to change behaviour (weakening belief that changing behaviour will reduce risk of disease because genetic is immutable).

Genetic Counseling↗

Information-seeking behaviour and psycho-social interactions during the genetic testing process.

OBJECTIVES: The first aim of this study was to investigate the information-seeking behaviour (ISB) of women attending cancer genetic consultations at which the possibility of BRCA testing is considered. We focused here specifically on ISB apart from the cancer genetic consultation, i.e. on what complementary sources of information about genetic testing were consulted and what factors were involved in this behaviour. The second aim was to study the role of the social network used by the patients to collect various opinions on which to base their decisions about being tested. METHODS: A prospective cohort study (2000-2002) was therefore carried out on all women attending a single cancer genetic clinic in France after a BRCA1/2 analysis had been proposed. Closed questionnaires were administered before and after the second cancer genetic consultation. The purpose of this consultation was to confirm the patient's decision to be tested. RESULTS: Results were analysed in 108 subjects (mean age 47 years, SD 11 years; 74% affected by breast/ovarian cancer). Prior to the 2nd consultation, 35.2% of the women had actively looked for information about BRCA1/2 testing, as compared to 25.0% afterwards. After multivariate adjustment by logistic regression, the pre-consultation ISB was found to be associated with greater satisfaction with the information about the psycho-social consequences of genetic testing [adjusted odds ratio (ORadj) 1.03, 95% confidence interval (CI) 1.01-1.06] (scale from 0 to 100) and about the certainty of being a gene carrier (ORadj 3.04, 95% CI 1.16-7.98). Those who actively looked for complementary information were also more often accompanied at the consultation by a family member (ORadj 4.82, 95% CI 1.85-12.56). The other variables tested (depression, coping, socio-demographic and medical characteristics) were not significant (p > 0.05). The role of the social network in the decision making process was perceived as being less helpful when the persons consulted tended to have neutral or unfavourable opinions about genetic testing. CONCLUSIONS: Few women actively sought complementary information about BRCA genetic testing in addition to the cancer genetic consultation. Those who did so differed from the others in terms of their social network and their satisfaction with the consultation. The cancer geneticist is the key actor in women's decision making about genetic testing.

Attitude to Health↗

New directions in the genetic mechanisms underlying nicotine addiction.

Major advances have been made in understanding nicotine addiction and smoking behaviour in recent years. In particular, evidence for the relative importance of genetic and environmental effects on smoking initiation and persistence has emerged from behaviour genetic studies. These data have supported evidence from molecular genetic studies for the role of particular candidate genes in tobacco dependence. Studies of the personality correlates of smoking behaviour suggest that these factors mediate the association between genetics and smoking initiation, while learning models of nicotine addiction suggest a role for dopaminergic genes in facilitating neuroadaptations associated with smoking persistence and development of nicotine dependence. Integrating these different avenues of research represents one of the most interesting and potentially fruitful ventures in the treatment of tobacco dependence.

Journal Article↗

Recent advances in embryonal tumours of the central nervous system.

INTRODUCTION: Embryonal tumours of the central nervous system (CNS) are the commonest malignant paediatric brain tumours. This group includes medulloblastomas, supratentorial primitive neuroectodermal tumours, atypical teratoid/rhabdoid tumours, ependymoblastomas, and medulloepitheliomas. Earlier, all these tumours were grouped under a broad category of primitive neuroectodermal tumours (PNETs). However, the current WHO classification (2000) separates them into individual types based on significant progress in the understanding of their distinctive clinical, pathological, molecular genetic, histogenetic, and behavioural characteristics. Furthermore, advances in histopathology and molecular genetics have shown great promise for refining risk assessment in these tumours, especially medulloblastomas, thus providing a more accurate basis for tailoring therapies to individual patients. Correlation of histological changes with genetic events has also led to a new model of medulloblastoma tumorigenesis. REVIEW: This review presents an updated comparative profile of these tumours, highlighting the clinical and biological relevance of the recent advances.

Age Distribution↗

Associations between nonshared environment and child problem behaviour.

BACKGROUND: Twin studies suggest that environmental effects on the development of child psychopathology largely involve nonshared environmental processes. However, the influence of the nonshared environment may have been overestimated, as the relationship between environment and behaviour may be genetically mediated. A direct measure of the nonshared environment (using the Sibling Inventory of Differential Experience - SIDE) was investigated in relation to child psychopathology, and tested for possible genetic mediation. METHOD: Parent-rated versions of the Child Behaviour Checklist (CBCL) and the SIDE were collected in 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the influence of SIDE scores on CBCL total problem scores, internalising symptoms, externalising symptoms and depressive symptom scores. Genetic mediation was assessed by examining interaction with zygosity in the association between SIDE scores and differences in CBCL scores (absence of interaction indicating no genetic mediation). RESULTS: The results revealed significant associations between SIDE dimensions on the one hand, and degree of internalising, externalising, depression and total symptom scores on the other. However, the effects were non-linear, and especially apparent for the extremes of differential environmental experience within twin pairs. Overall, there was no strong evidence for genetic mediation of associations between nonshared environment and symptoms. CONCLUSIONS: Direct, genetically unconfounded but skewed relationships may exist between nonshared environment on the one hand and behavioural differences on the other, although longitudinal data are necessary to determine the direction of effects.

Adolescent↗