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Forward genetic analysis of visual behavior in zebrafish.

The visual system converts the distribution and wavelengths of photons entering the eye into patterns of neuronal activity, which then drive motor and endocrine behavioral responses. The gene products important for visual processing by a living and behaving vertebrate animal have not been identified in an unbiased fashion. Likewise, the genes that affect development of the nervous system to shape visual function later in life are largely unknown. Here we have set out to close this gap in our understanding by using a forward genetic approach in zebrafish. Moving stimuli evoke two innate reflexes in zebrafish larvae, the optomotor and the optokinetic response, providing two rapid and quantitative tests to assess visual function in wild-type (WT) and mutant animals. These behavioral assays were used in a high-throughput screen, encompassing over half a million fish. In almost 2,000 F2 families mutagenized with ethylnitrosourea, we discovered 53 recessive mutations in 41 genes. These new mutations have generated a broad spectrum of phenotypes, which vary in specificity and severity, but can be placed into only a handful of classes. Developmental phenotypes include complete absence or abnormal morphogenesis of photoreceptors, and deficits in ganglion cell differentiation or axon targeting. Other mutations evidently leave neuronal circuits intact, but disrupt phototransduction, light adaptation, or behavior-specific responses. Almost all of the mutants are morphologically indistinguishable from WT, and many survive to adulthood. Genetic linkage mapping and initial molecular analyses show that our approach was effective in identifying genes with functions specific to the visual system. This collection of zebrafish behavioral mutants provides a novel resource for the study of normal vision and its genetic disorders.

Animals↗

Contributions of genes and environments to stability and change in externalizing and internalizing problems during elementary and middle school.

We examined longitudinally collected behavioral reports by teachers on a unique twin sample at the ages of 7, 8, 9, 10, 11, and 12 years. As twin and adoption studies implicate the role of genetic influence on behavioral problems found to be stable in epidemiological samples, the current study employs a developmental behavior genetic model to examine the extent to which genetic and environmental contributions to problem behaviors are stable and/or change during development. In this sample of 410 monozygotic (MZ) and 354 dizygotic (DZ) twins, MZ twins were rated as more similar than DZ twins on average. In general, boys were more frequently rated as displaying externalizing behaviors than were girls across each of the six observations, while girls' internalizing problems were found not to be significantly different from boys'. For both sexes, stability in externalizing problem behaviors was due to a single common genetic factor whose effects acted pleiotropically at each age in the presence of unique environmental influences that were transmitted from age-to-age. Change was largely due to uncorrelated age-specific non-shared environmental and additive genetic effects. Contributions to stability for internalizing problems were due to age-to-age transmission of earlier expressed genetic effects. Change for girls and boys internalizing problems were largely due to environmental experiences unique to siblings along with uncorrelated age-specific genetic effects. These results further inform the notion that individual environments are important factors in the etiology of problem behaviors, but suggest that heritable contributions to phenotypic stability are largely the same across middle childhood and early adolescence. Clinical implications of these findings are discussed.

Age Factors↗

Direct genetic and maternal influences on behavior and growth in two inbred mouse strains.

Newborn male DBA/2 and C57BL/6 mice were either crossfostered, fostered within strains, or, after handling, left with their own dams and compared for nine behavioral compenents observed in single animals at an adult age and for body weight measured at 4 weeks and 3 months. Many strain differences between the unfostered control groups emerged and these remained largely unchanged in comparisons between the infostered and between the outfostered groups. In neither infostered group were significant influences of fostering per se found. Some variation due to foster strain was detected mainly in the DBA outfostered group, namely, for 4-week body weight, rearing frequency, and locomotor activity, but no resemblance to the alien strain was brought about by this. Effects of litter occurred rarely. Unlike the C57BL strain, the DBAs showed a clear pattern of interdependence among exploratory acts. In spite of problems that may be attached to the crossfostering method, it was concluded that postnatal genotype-dependent maternal influences were rather unimportant as a source of variation in behavior and growth as measured between these two strains, relative to direct genetic effects and, possibly, prenatal factors.

Animals↗

Genetic analysis of the behavioral response to d-amphetamine in mice.

The ambulatory and rearing responses to d-amphetamine were studied in a battery of recombinant inbred strains and in three closely related strains: C57BL/6J, C57BL/10J, and C57BL/6By. Differences in the increase of ambulation (stimulation) caused by d-amphetamine were seen between C57BL/6By and the other two C57BL strains. Analysis of F1 and backcross matings suggests a one-gene model. A mutation at the genetic locus that affects the response to d-amphetamine seems to have taken place in the C57BL/6By strain. Strain differences in the decrease of rearing behavior (inhibition) produced by the drug were observed in recombinant inbred strains. Although the genetic analysis is not conclusive, it appears to be compatible with regulation by a single major gene. The two single-gene models reported here (one affecting the stimulatory response and the other the inhibitory response to d-amphetamine) may be useful in the study of neural mechanisms involved in stimulation and inhibition of behavior by d-amphetamine.

5-Hydroxytryptophan↗

Turtle mating systems: behavior, sperm storage, and genetic paternity.

As evidenced by the articles in this volume, a recent increase in interest in the mating systems of poikilothermic vertebrates has focused primarily on fishes, a few amphibians, and squamate reptiles. Turtles by contrast have received relatively little attention, yet they display a wide variety of mating behaviors and life-history characteristics that make them excellent candidates for addressing several aspects of genetic parentage that should contribute to a broader understanding of animal reproductive strategies. Here we focus on genetic studies of the mating systems and reproductive patterns of turtles, specifically with respect to multiple paternity and long-term sperm storage. These phenomena highlight the importance of a temporally extended perspective on patterns of individual reproductive success.

Animals↗

A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins.

BACKGROUND: Numerous twin studies on smoking behavior have shown that genetic and environmental factors play significant and approximately equal roles in the determination of smoking initiation (SI) and smoking persistence (SP). However, estimates of heritability (h2), shared (c2) and unique environmental effects (e2) from the literature display considerable variability for SI and SP, due most probably to differences in statistical analysis models, age, gender, sample size, origin of cohorts and measurement of smoking behavior. METHODS: A systematic literature search identified six studies for SI and 10 studies for SP. Data from these studies were obtained and re-analysed by meta-analytical techniques. RESULTS: For SI, our results indicate that the parameters h2, c2 and e2 are (mean +/- SEM): 0.37 +/- 0.04, 0.49 +/- 0.04 and 0.17 +/- 0.03 in male adults, and 0.55 +/- 0.04, 0.24 +/- 0.06 and 0.16 +/- 0.01 in female adults, respectively. These values were weighted by a combination of original estimates of variance from studies reporting variances plus estimated variances from studies where variances were not reported (called the combined variance method). Using the same approach for SP, we found that the parameters h2, c2 and e2 weighted by the combined variance method for the phenotype are (mean +/- SEM): 0.59 +/- 0.02, 0.08 +/- 0.04 and 0.37 +/- 0.03 in male adults, and 0.46 +/- 0.12, 0.28 +/- 0.08 and 0.24 +/- 0.07 in female adults, respectively. CONCLUSIONS: Our results indicate that genetic factors play a more significant role for SI but a less significant role for SP in female adults compared to male adults. Significant gender difference was also detected in shared environmental factors for SI and SP. However, no significant gender difference was detected for e2 for either phenotype. These findings suggest that genetic and environmental factors may contribute differently to the determination of smoking initiation and persistence in male and female smokers.

Adult↗

Gender-dependent modulation of brain monoamines and anxiety-like behaviors in mice with genetic serotonin transporter and BDNF deficiencies.

1. Brain-derived neurotrophic factor (BDNF) supports serotonergic neuronal development and our recent study found that heterozygous mice lacking one BDNF gene allele interbred with male serotonin transporter (SERT) knockout mice had greater reductions in brain tissue serotonin concentrations, greater increases in anxiety-like behaviors and greater ACTH responses to stress than found in the SERT knockout mice alone. 2. We investigated here whether there might be gender differences in these consequences of combined SERT and BDNF deficiencies by extending the original studies to female mice, and also to an examination of the effects of ovariectomy and tamoxifen in these female mice, and of 21-day 17-beta estradiol implantation to male mice. 3. We found that unlike the male SERTxBDNF-deficient mice, female SERTxBDNF mice appeared protected by their gender in having significantly lesser reductions in serotonin concentrations in hypothalamus and other brain regions than males, relative to controls. Likewise, in the elevated plus maze, female SERTxBDNF-deficient mice demonstrated no increases in the anxiety-like behaviors previously found in males. 4. Furthermore, female SERTxBDNF mice did not manifest the approximately 40% reduction in the expression of TrkB receptors or the approximately 30% reductions in dopamine and its metabolites that male SERTxBDNF did. After estradiol implantation in male SERTxBDNF mice, hypothalamic serotonin was significantly increased compared to vehicle-implanted mice. These findings support the hypothesis that estrogen may enhance BDNF function via its TrkB receptor, leading to alterations in the serotonin circuits, which modulate anxiety-like behaviors. 5. This double-mutant mouse model contributes to the knowledge base that will help in understanding genexgenexgender interactions in studies of SERT and BDNF gene polymorphisms in human genetic diseases such as anxiety disorders and depression.

Animals↗

A developmental-genetic analysis of aggressive behavior in mice (Mus musculus): III. Behavioral mediation by heightened reactivity or immobility?

This research was designed to investigate development and behavioral mediation in lines of ICR mice that have been selectively bred for aggressive behavior. General behavioral reactivity and behavioral immobility have been implicated as potential mediators by prior analyses of preattack interactions. To evaluate the separate roles of these dispositions, the emergence of attacks in genetically selected lines was tracked for 11 years by three levels of analysis: over successive generations, over development, and over dyadic interactions. Convergent outcomes were observed in all three levels with respect to two findings: (a) Robust line differences were obtained in attack behaviors, and (b) strong associations were found between line differences in attacks and line differences in behavioral immobility. Conversely, all three levels of analysis indicated a weak and inconsistent association between line differences in attacks and measures of social and nonsocial reactivity.

Aggression↗

Environmental and genetic components of stomatal behavior in two genotypes of upland cotton.

Two parental lines of Upland cotton (Gossypium hirsutum L.) plus their reciprocal F(1), F(2), and backcross populations were field-tested for environmental and genetic components of leaf diffusive resistance. Leaf resistance was measured with a diffusion porometer three times each day during 6 days in August. A large, consistent environmental component was present during the morning, afternoon, and evening, but the genetic component appeared mainly during the afternoon. Leaf water potential indicated that afternoon was the period of highest water stress. Genetic analyses revealed that leaf resistance was associated with both additive and dominance genetic variances, with an estimated narrow sense heritability of 25%. High leaf resistance was completely dominant to low resistance.

Journal Article↗

Genetic and environmental influences on behavioral disinhibition.

Comorbidity among childhood disruptive behavioral disorders is commonly reported in both epidemiologic and clinical studies. These problems are also associated with early substance use and other markers of behavioral disinhibition. Previous twin research has suggested that much of the covariation between antisocial behavior and alcohol dependence is due to common genetic influences. Similar results have been reported for conduct problems and hyperactivity. For the present study, an adolescent sample consisting of 172 MZ and 162 DZ twin pairs, recruited through the Colorado Twin Registry and the Colorado Longitudinal Twin Study were assessed using standardized psychiatric interviews and personality assessments. DSM-IV symptom counts for conduct disorder and attention deficit hyperactivity disorder, along with a measure of substance experimentation and novelty seeking, were used as indices of a latent behavioral disinhibition trait. A confirmatory factor model fit to individual-level data showed a strong common factor accounting for 16-42% of the observed variance in each measure. A common pathway model evaluating the genetic and environmental architecture of the latent phenotype suggested that behavioral disinhibition is highly heritable (a(2) = 0.84), and is not influenced significantly by shared environmental factors. A residual correlation between conduct disorder and substance experimentation was explained by shared environmental effects, and a residual correlation between attention deficit hyperactivity disorder and novelty seeking was accounted for by genetic dominance. These results suggest that a variety of adolescent problem behaviors may share a common underlying genetic risk.

Adolescent↗

Do aggressive and non-aggressive antisocial behaviors in adolescents result from the same genetic and environmental effects?

Antisocial behavior (ASB) in adolescents can broadly be separated into two forms; aggressive and non-aggressive. Both are heritable and it has been suggested that aggressive ASB is more heritable. The extent to which genes contribute to the correlation between the two is unknown. Structural equation modeling was applied to a population-based twin sample of 258 twins pairs aged 11-18 to estimate the heritability of each form of ASB and to estimate the extent to which the phenotypic correlation was the consequence of shared genes and environmental factors. Non-shared environment and genetic factors substantially influenced both forms of ASB. The heritability of aggressive (but not non-aggressive) ASB was significantly higher in girls than in boys. Combining both sexes, a model in which the genetic effects on aggressive and non-aggressive ASB were identical could be rejected. Our results suggest a partial genetic overlap with a specific genetic effect contributing to the variance of aggressive ASB and a stronger genetic effect on aggression in females than in males.

Adolescent↗

Evolutionary adaptationism: another biological approach to criminal and antisocial behaviour.

Although in a sense "genetic', the conceptual framework of evolutionary psychology, behavioural ecology and sociobiology is distinct from that of behaviour genetics. Considerable confusion has resulted from failures to recognize the distinctions. These disciplines are primarily concerned with the characterization of evolved adaptations, which are usually species-typical and environmentally contingent, so theory and research in these fields mainly concerns environmental rather than genetic sources of behavioural variation. Heritable behavioural variation is in general neither predicted by nor supportive of adaptationist theories. One might even say that substantial heritability of an apparently consequential attribute is a datum that challenges the tenets of adaptationism. Behaviour genetics and evolutionary adaptationism have had only limited mutual influence, but increasing knowledge of the processes by which genotypes affect behavioural phenotypes should facilitate development of a more synthetic approach.

Adaptation, Psychological↗

Intrinsic determinants of temperament.

Infant twins have been recruited to participate in a longitudinal assessment of temperament, beginning at three months of age. The twins are brought into a structured laboratory setting and are videotaped as they interact with the mother, with staff personnel, and with each other. The infant's temperament is rated from the videotapes, and additional data are obtained by having the parents fill out the Infant/Toddler Temperament Questionnaire at each visit. A neonatal assessment has also been done for most twins to obtain initial measures of irritability, reactivity and soothability. Monozygotic twins showed high concordance for irritability as neonates, and for ratings of emotional tone at 12 months. Monozygotic twins also tended to show synchronized patterns of change between ages. The questionnaire ratings correlated significantly with the laboratory ratings at six and 12 months, and this convergent linkage between two sources argues for a core temperament profile that manifests itself with some consistency.

Attention↗