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PubMed2000

Gender differences in association between serotonin transporter gene polymorphism and personality traits.

Since Lesch and colleagues reported an association between anxiety-related traits (Neuroticism) and a functional polymorphism in the serotonin transporter gene regulatory region (5-HTTLPR), there have been several reports on 5-HTTLPR and personality traits with both positive and negative results. The present study was a further attempt to replicate the original findings of Lesch et al. in a population of well-defined normal healthy subjects. In addition, a variable number tandem repeat polymorphism in the second intron was included in this study because it has recently been shown to act as a transcriptional regulator. Personality traits were evaluated in 186 unrelated normal subjects by the NEO Five Factor Inventory. The most important and novel finding of this study was a significant association of mean Neuroticism scores with the short allele of 5-HTTLPR in male subjects (t = 2.4, P = 0.018). We were thus able to replicate the finding of Lesch et al. of an association between serotonin transporter gene polymorphism (5-HTTLPR) and Neuroticism, but only in a male population. We also found a significant effect of gender on mean scores of Neuroticism [F = 3.9, degrees of freedom (df) = 1, 180, P = 0.05] and Agreeableness (F = 6.8, df = 1, 180, P = 0.01), but no significant effect of 5-HTTLPR genotype on Neuroticism (F = 0.87, df= 2, 180, P = 0.42) or Agreeableness (F = 0.35, df = 2, 180, P = 0.7). These findings suggest that gender differences exist in contribution of genetic factors to behavioural phenotypes. They may also explain the inconsistencies in previous reports on association of Neuroticism with 5-HTTLPR from studies using different proportions of male and female subjects.

Adult↗
PubMed2003

Sequential radiation of unrelated organisms: the gall fly Eurosta solidaginis and the tumbling flower beetle Mordellistena convicta.

Host shifts and the formation of insect-host races are likely common processes in the speciation of herbivorous insects. The interactions of goldenrods Solidago (Compositae), the gall fly Eurosta solidaginis (Diptera: Tephritidae) and the beetle Mordellistena convicta (Coleoptera: Mordellidae) provide behavioural, ecological and genetic evidence of host races that may represent incipient species forming via sympatric speciation. We summarize evidence for Eurosta host races and show that M. convicta has radiated from goldenrod stems to Eurosta galls to form host-part races and, having exploited the galler's host shift, has begun to differentiate into host races within galls. Thus, host-race formation has occurred in two interacting, but unrelated organisms representing two trophic levels, resulting in 'sequential radiation' (escalation of biodiversity up the trophic system). Distributions of host races and their behavioural isolating mechanisms suggest sympatric differentiation. Such differentiation suggests host-race formation and subsequent speciation may be an important source of biodiversity.

Animals↗
PubMed2003

Widespread occurrence of a domestic dog mitochondrial DNA haplotype in southeastern US coyotes.

Sequence analysis of the mitochondrial DNA control region from 112 southeastern US coyotes (Canis latrans) revealed 12 individuals with a haplotype closely related to those in domestic dogs. Phylogenetic analyses grouped this new haplotype in the dog/grey wolf (Canis familiaris/Canis lupus) clade with 98% bootstrap support. These results demonstrate that a male coyote hybridized with a female dog, and female hybrid offspring successfully integrated into the coyote population. The widespread distribution of this haplotype from Florida to West Virginia suggests that the hybridization event occurred long ago before the southeastern USA was colonized by coyotes. However, it could have occurred in the southeastern USA before the main front of coyotes arrived in the area between male coyotes released for sport and a local domestic dog. The introgression of domestic dog genes into the southeastern coyote population does not appear to have substantially affected the coyote's genetic, morphological, or behavioural integrity. However, our results suggest that, contrary to previous reports, hybridization can occur between domestic and wild canids, even when the latter is relatively abundant. Therefore, hybridization may be a greater threat to the persistence of wild canid populations than previously thought.

Animals↗
PubMed2005

Antisense oligonucleotides as therapeutics for hyperlipidaemias.

Hyperlipidaemia, due to elevations of low-density lipoprotein cholesterol (LDL-C) or triglycerides (TGs), is recognised as a significant risk factor contributing to the development of coronary heart disease (CHD), the leading cause of morbidity and mortality in the Western world. Even though a variety of established antihyperlipidaemic agents are available, the majority of high-risk patients do not reach their lipid goals, indicating the need for new and more effective therapeutics to be used alone or as combination agents with existing drugs. Antisense oligonucleotides (ASOs), designed to specifically and selectively inhibit novel targets involved in cholesterol/TG homeostasis, represent a new class of agents that may prove beneficial for the treatment of hyperlipidaemias resulting from various genetic, metabolic or behavioural factors. This article describes the antisense technology platform, highlights the advantages of these novel drugs for the treatment of hyperlipidaemia and reviews the current research in this area.

Animals↗
PubMed1988

Genetic aspects of tumour metastasis.

The application of techniques for the transfer of genetic material between cells when used with recombinant DNA technologies and gene cloning procedures hold exciting possibilities for the genetic analysis of the metastatic behaviour of tumour cells. So far these genetic studies have produced confusing results, but some of the problems have been defined more clearly. For a more complete understanding of the metastatic phenotype a more critical analysis of the models used to mimic the process and a greater appreciation of the deficiencies in the techniques applied to study it are necessary.

Animals↗
PubMed2004

The importance of learning young: the use of nesting material in laboratory rats.

Unlike mice, adult laboratory rats do not spontaneously build nests when nesting material is offered. As a result, nesting material is often regarded as unsuitable environmental enrichment for laboratory rats. Wild rats and pet rats, however, have been observed to build complex nests from nesting material at hand. It was hypothesized that nest building in rats is an acquired behaviour, rather than genetically predisposed. To test this hypothesis, the progeny of three Wistar rats provided with nesting material (Kleenex tissues) during pregnancy and three standard-housed rats were divided in 34 same-sex couples with access to nesting material: (1) from the age of 8 weeks (n=7); (2) from weaning (n=8); (3) from birth (n=17). The latter were subdivided into two groups after weaning, one provided with Kleenex tissues (n=9), the other with Enviro-dri (n=8). At the age of 12 weeks, all couples were provided with both types of nesting material for one week. Amount, shape, and soiling of the nesting material were scored on weekdays, and behaviour of the rats was scored twice weekly. Results indicated that the older the rats were when first provided with nesting material, the greater the amount of nesting material eaten and soiled, and the nests built were less elaborate. Overall, Enviro-dri was eaten less than Kleenex tissues. It is concluded that rats need to learn the proper use of nesting material. When provided from birth, nesting material is a suitable type of environmental enrichment for laboratory rats.

Aging↗
PubMed2006

Energy balance and food intake: the role of PPARgamma gene polymorphisms.

Mechanisms regulating energy balance involve complex interactions between genetic, environmental and behavioural (learnt and intrinsic) factors. Genotype may drive the partitioning of energy metabolism and predispose to site-specific adiposity, culminating in a state of energy imbalance. One candidate gene with a direct link to adiposity is the peroxisome proliferator-activated receptor gamma (PPARG) gene. PPARG is a cell nuclear receptor expressed almost exclusively in adipose tissue that regulates adipocyte differentiation, lipid metabolism and insulin sensitivity. PPARgamma appears to be a key regulator of energy balance, with polymorphisms on the PPARG gene linked to obesity and effects on body composition. Our research has confirmed an association between the pro12ala allele and reduced incidence of obesity in pre-pubertal children and there are strong associations between genetic variation at the PPARG locus and percentage body fat. Moreover, our evidence suggests that PPARG C-681G and pro12ala polymorphisms display opposing effects in terms of growth phenotype, with pro12Ala associated with deficient energy utilisation, leading to reduced growth and the G-681 variant associated with accelerated growth compared with wildtypes. Common differences in this gene have also been associated with variations in body weight in response to dietary macronutrients. Preliminary evidence suggests that PPARG variants may even be involved in the control of short term energy compensation. Taken together these data suggest that the role of PPARG is varied and complex, influencing fat deposition and growth velocity early in life, with potential impact in the control of energy intake and appetite regulation, and could provide a key target for future research and anti-obesity agents.

Adiposity↗
PubMed1980

The recombinant inbred strains: a tool for the genetic analysis of differences observed in the self-stimulation behaviour of the mouse.

The self-stimulation behaviour (ICSS) in the lateral hypothalamus of mice was studied using 5 recombinant inbred strains having the DBA/2 and BLAB/c lines for their parental origin. Two of these recombinant inbred strains behave like the recessive parental line (BALB/c) while the three others have a performance level similar to that of the dominant (DBA/2) parent. This division suggests that there is a major gene which determines the difference in performance between the two parental lines. The mean value for the self-stimulation threshold is negatively correlated with the value of the performance. The sensitivity to convulsions, which interrupt ICSS behaviour above certain current intensities, is under the control of a genetic determinant independent, but more complex, than the one which controls the level of performance.

Animals↗
PubMed1975

Modern trends in human genetics.

Every physician is deeply concerned with the tremendous advances in genetics during the last decade. Through 'gene surgery' DNA transplantation on both somatic and germinal tissue is feasible. Thus, genetic determinism is no longer ineluctable. Tissue culture is a tool to avoid cellular degeneration and achieve cellular immortality.Precise chromosome identification allows one to follow transmission from generation to generation, as well as human gene mapping. Through clinical and especially biochemical methods, genetic entities are dissected more accurately. Ecological genetics studies the risk inherent with drugs, radiations, chemicals and a myriad of environmental factors. On the other hand, behavioral genetics tend to specify the part of the genetic set in human behaviour. Computerized programmes are responsible for some significant advances in population genetics. Prenatal diagnosis, newborn screening programmes, heterozygote detection, and so on, and add a new dimension to genetic counseling. Knowing the part of inheritance in retinal affections, our speciality will greatly benefit from these recent advances in genetics.

Amniocentesis↗
PubMed1989

[The sociobiological ideas of Arthur Schopenhauer].

Starting from the basic ideas of sociobiology we prove that Schopenhauer, in his "Metaphysics of Sexual Love", has to pass for a precursor of sociobiological thinking. Several consequences of this parallel are discussed: The quest for strategic principles of organismic growth and evolution as a positive characteristic of both approaches--the hypothesis of a dominant genetic determination of human behaviour as an outcome of a typical bourgeois view of mankind connecting Schopenhauer and sociobiologists--the necessity of taking into consideration biological predispositions of flexible (learned) behaviour as elements of sociobiological models enjoying the same rights as genetical ones--the utility of Schopenhauer's natural philosophy for the purpose of complementing historical knowledge of many disciplines (also psychology).

Biology↗
PubMed2001

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Adult↗
PubMed1985

Genetic analysis of strain differences in pre-laying behaviour in battery cages.

The behaviour of hens of two strains during the 10 min before laying in battery cages was studied. Hens of one strain typically exhibited backward-and-forward pacing before laying. Hens of the other strain did not pace and tended to sit. Individual hens of both strains were consistent in their expression of pacing and sitting before laying. There was genetic variation in the expression of both pacing and sitting before laying, and both traits responded to selection. Crosses between the two lines indicated additive genetic variation in the expression of sitting behaviour and non-additive variation in the expression of pacing behaviour.

Animals↗
PubMed2000

Dissecting the behaviour of transgenic mice: is it the mutation, the genetic background, or the environment?

Increasingly sophisticated and precise molecular genetic tools are applied to mice in order to study the cellular mechanisms underlying higher brain functions, including learning and memory. However, several studies have produced unclear or conflicting results. One reason for this is that performance in the behavioural tests used to assess learning and memory is influenced by various non-cognitive phenomena and can thus easily be affected by mutations through mechanisms unrelated to memory function. We conducted principal component analysis on data from 3003 mice tested using a standardized protocol to demonstrate this for the Morris swimming navigation test, one of the most widely used paradigms to assess memory and hippocampal function. In addition, we present a meta-analysis showing that genetic background and environment alone produce sufficient variation to span the range of most, if not all, behavioural variables and can thus easily mask or fake mutation effects if genetic studies are not designed properly. We suggest that the chance of obtaining useful results is maximized if behavioural deficits are differentiated by combining complementary behavioural protocols and by analysing multiple complementary parameters in each of them. Mutation effects must be contrasted statistically against the influences of genetic background and environment. In many situations, this is most efficiently achieved if (i) mutations are backcrossed to and maintained in one or (preferably) two well-characterized, commonly available inbred strains and (ii) if mutant and wild-type littermates are analysed on a hybrid or mixed genetic background, that is in F1 or F2 generations derived from the inbred stocks.

Animals↗
PubMed2006

Genetic studies in variegate porphyria in Spain. Identification of gene mutations and family study for carrier detection.

BACKGROUND: First, to establish the mutations of the protoporphyrinogen-oxidase (PPOX) gene in four Spanish patients with variegate porphyria (VP). Second, study of carrier status detection in the families, including a four-generation Balearic family. Third, evaluation of the results of carrier detection screening methods. DESIGN: Blood samples of four patients and of 139 members belonging to four families, including four generations of a Balearic family were processed for mutation analysis of the 13 exons of PPOX gene. Biochemical studies were performed together (blood and faecal porphyrin analysis) and plasma fluorescence scanning for 626 nm peak emission detection. A questionnaire regarding clinical manifestations was submitted to all family members studied. RESULTS: Single strand conformational analysis (SSCP) of DNA allowed the detection of the following mutations: W224R, 746delT: exon 7, 1077-1082insC: exon 10, and IVS6+2T-->A. Mutation was present in 19 of the 139 members of the families studied. Clinical manifestations or biochemical alterations were checked in the carriers detected and found as not relevant or not present. Only 11 members of the 19 mutation-bearing individuals showed plasma fluorescence PV peak positivity. CONCLUSION: Demonstration of gene mutation is the most reliable means of detecting carriers in studies of variegate porphyria families. DNA analysis is the most sensitive carrier detection method and also allows transmission behaviour of the genetic defect to be established in successive generations of the affected families.

Adult↗
PubMed2002

Behavioural determinants of gene flow in malaria vector populations: Anopheles gambiae males select large females as mates.

BACKGROUND: Plasmodium-refractory mosquitoes are being rapidly developed for malaria control but will only succeed if they can successfully compete for mates when released into the wild. Pre-copulatory behavioural traits maintain genetic population structure in wild mosquito populations and mating barriers have foiled previous attempts to control malaria vectors through sterile male release. METHODS: Varying numbers of virgin male and female Anopheles gambiae Giles, from two strains of different innate sizes, were allowed to mate under standardized conditions in laboratory cages, following which, the insemination status, oviposition success and egg batch size of each female was assessed. The influence of male and female numbers, strain combination and female size were determined using logistic regression, correlation analysis and a simple mechanistic model of male competition for females. RESULTS: Male An. gambiae select females on the basis of size because of much greater fecundity among large females. Even under conditions where large numbers of males must compete for a smaller number of females, the largest females are more likely to become inseminated, to successfully oviposit and to produce large egg batches. CONCLUSIONS: Sexual selection, on the basis of size, could either promote or limit the spread of malaria-refractory genes into wild populations and needs to be considered in the continued development and eventual release of transgenic vectors. Fundamental studies of behavioural ecology in malaria vectors such as An. gambiae can have important implications for malaria control and should be prioritised for more extensive investigation in the future.

Animals↗
PubMed2000

Complex social organization reflects genetic structure and relatedness in the cooperatively breeding bell miner, Manorina melanophrys.

The cooperatively breeding bell miner, Manorina melanophrys, differs from most other cooperative breeding species in the complexity of its social system, where discrete social organization occurs on at least three levels. Microsatellite markers were used to investigate the degree of genetic structure underlying the social organization of M. melanophrys by comparing colonies, coteries and nest contingents. The genetic data confirmed behavioural observations of M. melanophrys living in male kin-based groups between which females disperse short distances to breed. Estimates of FST revealed restricted gene flow between eight colonies located within 30 km that was significantly associated with geographical distance when the two most distant colonies were included. Within a high density colony significant differences were found between coteries; analysis of the degree of relatedness between coterie members showed that this is due to related individuals associating preferentially with each other. Similarly, the contingent of individuals attending a nest were generally close relatives of the young they were aiding, supporting models invoking kin selection as the selective agency mediating helping.

Animals↗
PubMed2004

The dorsal diencephalic conduction system of zebrafish as a model of vertebrate brain lateralisation.

Lateralisation is an attractive and intriguing feature of the vertebrate CNS studied for decades in the different disciplines of the neurosciences. Due to the complexity of the phenomena and intrinsic limitations of the approaches used to date, it has been difficult to establish useful links between the different, and usually distant, levels of lateralisation e.g. between genetics, morphology, physiology and behaviour. Recently, the dorsal diencephalon of the teleost zebrafish has emerged as a valuable model to begin addressing this issue and as a result unravel the role of vertebrate CNS lateralisation. Zebrafish is a well-established genetic system that allows a 'bottom up' ('gene to behaviour') approach to the study of lateralisation. In fact, it is the single vertebrate system to date in which asymmetric gene expression in the brain has been directly linked to asymmetric morphology. Zebrafish offers several experimental advantages that allow the study of brain lateralisation using a wide range of experimental tools, from study of gene function through in vivo analysis of morphology and physiology to behavioural assessments. Altogether, these features will allow the establishment of operational links between lower (genetics and morphology) and upper (physiology and behaviour) levels of brain lateralisation.

Animals↗
PubMed2005

Differential sensitivity to the motor and hypothermic effects of the GABA B receptor agonist baclofen in various mouse strains.

RATIONALE: Comparison of different mouse strains can provide valuable information about the genetic control of behavioural and molecular phenotypes. Recent evidence has demonstrated the importance of GABA B receptors in anxiety and depression. Investigation of the phamacogenetics of GABA B receptor activation may aid in the understanding of mechanisms underlying the role of GABA B in affect. OBJECTIVES: The aim of current study was to determine the relative sensitivity of different mouse strains to GABA B receptor agonism in two models of GABA B receptor function, namely hypothermia and motor incoordination. METHODS: Mice each from 11 strains (BALB/cByJIco, DBA/2JIco, OF1, FVB/NIco, CD1, C3H/HeOuJIco, 129/SvPasIco, NMRI, C57BL/6JIco, A/JOlaHsd and Swiss) were trained to walk on a rotarod for 300 s. On the following day, mice received 0, 3, 6 or 12 mg/kg of L: -baclofen PO. Rectal temperature and rotarod performance were measured at 0, 1, 2 and 4 h after drug application. RESULTS: L: -Baclofen produced a significant dose-dependent hypothermia and ataxia in most, but not all, mouse strains examined. The magnitude and duration of response was influenced by strain, with mice of the 129/SvPasIco strain showing largest hypothermic response to 12 mg/kg l-baclofen and C3H/HeOuJIco the lowest, whereas the BALB/cByJIco strain demonstrated greatest ataxic response on the rotarod, and NMRI the least. Interestingly, some strains (notably C3H/HeOuJIco) had marked differential hypothermic and ataxic responses, with minimal body temperature responses to L: -baclofen but significant ataxia on the rotarod observed. CONCLUSION: There is differential genetic control on specific GABA B receptor populations that mediate hypothermia and ataxia. Further, these studies demonstrate that background strain is an important determinant of GABA B receptor mediated responses, and that hypothermic and ataxic responses may be influenced by independent genetic loci.

Animals↗