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PubMed1989

Behaviour of the genetically hypertensive rats of Koletsky type in holeboard and in elevated plus-maze: effect of scopolamine and nicergoline treatment.

The experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats which were developed by Koletsky (12); both sexes were used. The behavior in control and in Scopolamine and Nicergoline treated rats was traced in the holeboard and in the elevated plus-maze. In the control animals, when compared to the normotensive rats of Wistar strain, the genetically hypertensive rats of both sexes show elevated aversion towards open space and hight in the elevated plus-maze, reduced time spent head dipping in holeboard, reduced rate of habituation of locomotor-exploratory activity, and the elevated total time of locomotor-exploratory activity in holeboard. Scopolamine at dose 0.25 mg/kg b. w. and Nicergoline at dose 4 mg/kg b. w. reduced the aversion towards the open space and hight in elevated plus-maze only in the genetically hypertensive rats of both sexes. Both drug when applied simultaneously show mutual potentiation in the genetically hypertensive rats. Both drugs when applied separately or simultaneously caused elevation of time spent head dipping, i. e., elevation of directed exploration. Nicergoline caused decrease and Scopolamine caused increase of total time of exploratory activity in holeboard. Nicergoline increases the rate of habituation of the locomotor-exploratory activity in the males of normotensive rats and in the genetically hypertensive rats of both sexes. Scopolamine remained without effect in the normotensive rats of both sexes, elevated the rate of habituation in the genetically hypertensive males.

Animals↗
PubMed1987

The sampling theory of neutral alleles and an urn model in population genetics.

The behaviour of a Pólya-like urn which generates Ewens' sampling formula in population genetics is investigated. Connections are made with work of Watterson and Kingman and to the Poisson-Dirichlet distribution. The order in which novel types occur in the urn is shown to parallel the age distribution of the infinitely many alleles diffusion model and consequences of this property are explored. Finally the urn process is related to Kingman's coalescent with mutation to provide a rigorous basis for this parallel.

Alleles↗
PubMedDate not supplied

A histochemical study of the distribution of aldehyde dehydrogenase activity in brain structures of rats with genetically different alcohol-related behaviour.

Brain samples from rats genetically selected for high or low voluntary alcohol intake (AA and ANA strains) or for differences in alcohol-induced motor incoordination (AT and ANT strains) were analyzed by histochemistry for aldehyde dehydrogenase (EC 1.2.1.3; ALDH) activity in various CNS structures. All strains exhibited the highest ALDH activities in neurons of the mesencephalic tract of trigeminal nerve nucleus and in spinal cord motoneurons, while the lowest activities were observed in the somatosensory cortex. Although the general distribution pattern of ALDH activity was similar in the genetically selected strains, some potentially important differences were observed. AA rats with high voluntary alcohol consumption had lower ALDH activity (with acetaldehyde as substrate) in the neuropil of the olfactory tubercle but higher activity (with benzaldehyde as substrate) in the spinal cord motoneurons, Purkinje cells and capillary endothelium of the cerebellum as compared to the corresponding structures from the alcohol avoiding ANA rats. Alcohol-resistant AT rats had higher ALDH activity, with benzaldehyde, in most CNS structures than did the alcohol-sensitive ANT's, significantly so in the lamina II of the somatosensory cortex and the neurons of the lateral hypothalamic area. This relationship was also found with acetaldehyde as substrate in the neurons of the hypothalamic arcuate nuclei and in cerebellar capillaries, but the ANT's had the higher activity in the neurons of the cerebral cortex V lamina. We suggest that some of the differences observed may relate to the differences between the rat strains with respect to voluntary alcohol intake and alcohol-induced motor incoordination.

Alcohol Drinking↗
PubMed1998

Suicidal behaviour: an epidemiological and genetic study.

BACKGROUND: Psychiatric history, familial history of suicide attempts, and certain traumatic life events are important predictors of suicidal thoughts and behaviour. We examined the epidemiology and genetics of suicidality (i.e. reporting persistent suicidal thoughts or a plan or suicide attempt) in a large community-based sample of MZ and DZ twin pairs. METHOD: Diagnostic telephone interviews were conducted in 1992-3 with twins from an Australian twin panel first surveyed in 1980-82 (N = 5995 respondents). Data were analysed using logistic regression models, taking into account twin pair zygosity and the history of suicidality in the respondent's co-twin. RESULTS: Lifetime prevalence of suicidal thoughts and attempts was remarkably constant across birth cohorts 1930-1964, and across gender. Major psychiatric correlates were history of major depression, panic disorder, social phobia in women, alcohol dependence and childhood conduct problems. Traumatic events involving assault (childhood sexual abuse, rape or physical assault) or status-loss (job loss, loss of property or home, divorce), and the personality trait neuroticism, were also significantly associated with suicide measures. Prevalence of serious suicide attempts varied as a function of religious affiliation. After controlling for these variables, however, history of suicide attempts or persistent thoughts in the respondent's co-twin remained a powerful predictor in MZ pairs (odds ratio = 3.9), but was not consistently predictive in DZ pairs. Overall, genetic factors accounted for approximately 45% of the variance in suicidal thoughts and behaviour (95% confidence interval 33-51%). CONCLUSIONS: Risk of persistent suicidal thoughts and suicide attempts is determined by a complex interplay of psychiatric history, neuroticism, traumatic life experiences, genetic vulnerability specific for suicidal behaviour and sociocultural risk or protective factors.

Adult↗
PubMed2026

The contribution of common and rare genetic variation to emotional and behavioural symptoms in childhood and adolescence.

Genetic factors influence vulnerability to common mental health conditions, but their role in early-life mental health remains understudied. We analysed genotype array (n&#x2009;=&#x2009;4709-6687) and exome sequence data (n&#x2009;=&#x2009;4500-5424) from the Millennium Cohort Study (MCS) and Avon Longitudinal Study of Parents and Children (ALSPAC) to assess the contribution of common variants and rare deleterious coding variants to internalising and externalising symptoms across development. In longitudinal analysis spanning ages 5-17 years, we identified several associations between common genetic variation, indexed by polygenic indices (PGIs), and both symptom domains that generally remained stable across development. Effect sizes were modest, with the largest estimates observed for PGIs for attention deficit hyperactivity disorder (ADHD) and externalising behaviour with externalising symptoms (&#x3b2;&#x2009;=&#x2009;0.13-0.18; p-adj<3.5&#xd7;10&#x207b;29). Evidence for direct genetic effects was strongest for externalising symptoms, including for associations with the ADHD and externalising behaviour PGIs. Concordant results were observed in the Born in Bradford cohort. A higher exome-wide burden of deleterious rare variants was associated with increased externalising and internalising symptoms (&#x3b2;&#x2009;=&#x2009;0.04-0.06, p-adj<0.03); within-family models indicated direct genetic effects on externalising in MCS (&#x3b2;&#x2009;=&#x2009;0.07; p&#x2009;<&#x2009;0.05, p-adj>0.05) and on internalising symptoms in ALSPAC (&#x3b2;&#x2009;=&#x2009;0.12, p-adj<0.02). Common and rare genetic variants contributed independently, jointly explaining 2% of the variance in internalising and 5-7% in externalising symptoms. This study shows that early-life mental health is influenced by both common and rare genetic variation, with several associations explained by direct genetic effects.

Journal Article↗
PubMed2006

Genetic selection on a behavioural fear trait is associated with changes in heart rate variability in quail.

This study investigated whether genetic selection on a divergent behavioural trait of fearfulness (tonic immobility duration) was related to changes in the nervous control of the heart. Quail selected for either long or short tonic immobility (LTI or STI, respectively) duration was compared with an unselected control line (CTI). The autonomic control of the heart was assessed by heart rate variability analysis and pharmacological blockades. Quail were surgically fitted with a telemetric device. Heart rate before injection did not differ between the three lines. The vagal-sympathetic effect (VSE) at rest differed significantly from 1 in CTI and STI quail, suggesting that parasympathetic activity was dominant. In LTI quail, VSE did not differ from 1, suggesting a balance between parasympathetic and sympathetic activities. The intrinsic heart rate reached after the successive injections of propranolol and atropine did not differ between lines and was higher than the heart rate at rest in STI, which was in line with results of VSE at rest. After atropine injection, the sympathetic activity indicated by the low-frequency power was lower in CTI than in the two selected quail. After propranolol injection, the parasympathetic activity indicated by the root of the mean squares of successive differences and the high-frequency power was higher in STI than in CTI and LTI quail. Selection on tonic immobility duration thus appears to be associated with changes in the sympathovagal control of the heart, which may influence behavioural responses to stressful situations.

Animals↗
PubMed2006

The association of DNA sequence variation at the MAOA genetic locus with quantitative behavioural traits in normal males.

Monoamine oxidase A (MAOA) catalyses the oxidative deamination of biogenic amines including neurotransmitters, mainly norepinephrine and serotonin in the brain and peripheral tissues. A nonsense mutation in the gene was shown to be involved in a rare X-linked behavioural syndrome, which includes impaired impulse control, aggression and borderline mental retardation (Brunner syndrome). Several recent studies have shown the association of genetic variation of a VNTR in the gene promoter with various pathological behavioural traits. In the present study the association of MAOA genetic variation with a large set of quantitative behavioural traits in normal individuals has been examined. DNA samples from 421 unrelated males were genotyped for 14 SNPs and for the promoter VNTR at the MAOA locus. An additional 16 SNPs were genotyped at apparently neutral loci across the X chromosome to serve as a genomic control for possible false positive associations due to population structure. Behavioural traits were measured using the NEO psychometric questionnaire, which is based on a 5-axis model of personality, and consists of 30 different quantitative traits. There was a robust association of the A2 ("straightforwardness") facet with common allelic variants at the promoter VNTR. Most of the tested traits were not associated with the VNTR despite reasonable power, thus demonstrating that the VNTR influence on quantitative behavioural traits in normal males may be very specific. In contrast, several traits of the C ("conscientiousness") axis were associated with less common SNP-defined haplotypes. Hence, it appears that common genetic variation at the VNTR contributes to the behavioural attribute of "straightforwardness", while rare haplotypes defined by SNPs downstream of the transcription start site may contribute to "conscientiousness". This study is used to address the validation, interpretation and limitation of genetic association studies of quantitative behavioural traits.

Black or African American↗
PubMed1977

Regional acetylcholine turnover rates in the brains of three inbred strains of mice: correlation with some interstrain behavioural differences.

The hypothesis that the genetically determined behavioural differences which exist between the inbred mouse strains Balb/c, DBA/2 and C57Bl/6 may be related to differences in acetylcholine metabolism in certain regions of the brain has been tested. In vivo ACh turnover rates have been measured in three regions (hippocampus, caudate nucleus and frontal-parietal cortex) of the brains of each strain by following the rate of formation of labelled ACh, in these regions, after a pulse intravenous injection of a tracer dose of 3H labelled choline. Focused microwave procedures were used for the rapid fixation of brain tissue and Ch and ACh radioactivities were determined following their electrophoretic separation. Steady-state concentrations of Ch and ACh were measured by a sensitive radio-enzymatic method. Significant interstrain differences in ACh turnover rates are reported for each of the brain regions studied with the order of metabolic activity being Balb/c greater than DBA/2 greater than C57 Bl/6 in each case. These results are interpreted as being in agreement with previous reports on correlations between learning ability or locomotor activity and regional activities of choline acetyltransferase in the brains of these inbred strains. The correlations between the in vivo ACh turnover rates and (1) interstrain differences in behavioural measures and (2) regional choline acetyltransferase activities are discussed.

Acetylcholine↗
PubMed2005

A microarray data-based semi-kinetic method for predicting quantitative dynamics of genetic networks.

BACKGROUND: Elucidating the dynamic behaviour of genetic regulatory networks is one of the most significant challenges in systems biology. However, conventional quantitative predictions have been limited to small networks because publicly available transcriptome data has not been extensively applied to dynamic simulation. RESULTS: We present a microarray data-based semi-kinetic (MASK) method which facilitates the prediction of regulatory dynamics of genetic networks composed of recurrently appearing network motifs with reasonable accuracy. The MASK method allows the determination of model parameters representing the contribution of regulators to transcription rate from time-series microarray data. Using a virtual regulatory network and a Saccharomyces cerevisiae ribosomal protein gene module, we confirmed that a MASK model can predict expression profiles for various conditions as accurately as a conventional kinetic model. CONCLUSION: We have demonstrated the MASK method for the construction of dynamic simulation models of genetic networks from time-series microarray data, initial mRNA copy number and first-order degradation constants of mRNA. The quantitative accuracy of the MASK models has been confirmed, and the results indicated that this method enables the prediction of quantitative dynamics in genetic networks composed of commonly used network motifs, which cover considerable fraction of the whole network.

Amino Acid Motifs↗
PubMed2004

Genetic evidence reveals density-dependent mediated success of alternative mating behaviours in the European bitterling (Rhodeus sericeus).

The reproductive success of alternative mating behaviours may vary within and among populations in relation to environmental factors and demographic parameters. We used behavioural and genetic data to investigate how male density affects reproductive success of territoriality and sneaking in the European bitterling (Rhodeus sericeus, Cyprinidae), a freshwater fish that spawns on the gills of living freshwater mussels. Keeping the number of spawning sites constant, we manipulated male densities in laboratory and mesocosm experiments. We showed that sneaked fertilizations were common in R. sericeus, and that they increased significantly with male density. Territorial mating was almost 17 times more successful than sneaking at the lowest male density treatment, and still 2-3 times more successful at intermediate densities. However, both behaviours conferred the same fitness pay-off at the highest male density. While the success of territorial males declined with male density, the success of individual sneaking males remained constant across densities. Notably, the capacity of territorial males to outcompete sneakers by preoviposition sperm loading was the best predictor of male reproductive success, rather than aggression, body size or postoviposition ejaculation.

Animals↗
PubMed2002

Genetic basis of anxiety-like behaviour: a critical review.

The way genetic and/or environmental factors influence psychiatric disorders is an enduring question in the field of human psychiatric diseases. Anxiety-related disorders provide a relevant example of how such an interaction is involved in the aetiology of a psychiatric disease. In this paper we review the literature on that subject, reporting data derived from human and rodent studies. We present in a critical way the animal models used in the studies aimed at investigating the genetic basis of anxiety, including inbred mice, selected lines, multiple marker strains, or knockout mice and review data reporting environmental components influencing anxiety-related behaviours. We conclude that anxiety is a complex behaviour, underlined not only by genetic or environmental factors but also by multiple interactions between these two factors.

Animals↗
PubMed1996

[Relation between loss of heterozygosity at APC and MCC genetic loci and biological behaviour of gastric carcinoma].

In order to detect loss of heterozygosity (LOH) at APC and MCC genetic loci in gastric carcinoma, the authors established a micro-wax-mediated hot start PCR technique. This method allowed a specific gene amplification, and it was useful especially in the amplification of formalin-fixed or stained tissues. In 44 cases of gastric cancer, 29 cases were informative of the APC locus. LOH was found in 8 cases (27.6%): 2 cases in 2 moderately well-differentiated cancer, 2 cases in 13 differentiated cancer, and 4 cases in poorly-differentiated cancer. One of the 3 cases of gastric cancer at early stage also showed LOH. LOH at MCC locus was detected in only 2 of the 25 (8.0%) gastric cancer patients informative. These data suggest that abnormality of APC gene plays a role in the tumorigenesis of gastric cancer and the change may occur at the early stage of tumor development.

Adenocarcinoma↗
PubMed2000

Genetic dissection of nicotine-related behaviour: a review of animal studies.

Nicotine has a broad spectrum of behavioural effects. A considerable body of data has emerged indicating genetic factors regulate the behavioural effects of nicotine. Experimental genetic techniques have been invaluable in generating knowledge on the interrelationship of genetic factors and behavioural responsiveness to nicotine. Three different approaches have been invoked to explore the relationship of genetic factors to response to nicotine. Firstly, the classical genetic tool of inbred lines has been exploited to delineate genetic influences in the effects of nicotine. Secondly, the use of selectively bred lines has been profitably employed to reveal genetic differences in behavioural responses, such as cognition and exploration, to nicotine. These approaches have also provided useful information on the contribution of genetic factors influencing nicotinic receptors function. Finally the molecular genetic technique of gene targetting to create mice with null mutations of specific genes in the central nervous system, which is having a tremendous impact in drug addiction research, has also been employed to gain insight into the molecular and cellular basis of nicotine action. These techniques are proving to be invaluable in dissecting the role of different subunits of the nicotinic acetylcholine receptors on behaviour. This paper provides a survey of the animal studies that have used the above mentioned techniques to gain insight into genetic basis of the behavioural effects of nicotine.

Animals↗
PubMed1992

Reproductive behaviour and prenatal diagnosis following genetic termination of pregnancy in women of advanced maternal age.

One hundred and fifty-one women of advanced maternal age who underwent genetic termination of pregnancy (TOP) were studied for their reproductive behaviour and the type of procedure for prenatal diagnosis in a subsequent pregnancy. A total of 59 women (39 per cent) had a further pregnancy. In all continuing pregnancies prenatal diagnosis was performed, of which 75 per cent consisted of chorionic villus sampling (CVS). Reproductive behaviour following a genetic termination was negatively correlated with maternal age and parity. Both reproductive behaviour and the choice to undergo a diagnostic procedure in the next pregnancy were independent of the type of diagnostic procedure in the previous affected pregnancy.

Abortion, Therapeutic↗