Showing papers in "Behavior Genetics in 2002"
TL;DR: There were large strain differences in all the measures collected, with at least a two-fold difference between strains with the lowest and the highest trait values.
Abstract: Male mice from 28 inbred strains (129P3/J, A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57L/J, CAST/Ei, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/HlJ, LP/J, NOD/LtJ, NZB/BlNJ, P/J, PL/J, RBF/DnJ, RF/J, RIIIS/J, SEA/GnJ, SJL/J, SM/J, SPRET/Ei, and SWR/J) were fed chow and had access to two water bottles Body weight, food intake, water intake, and drinking spout side preference were measured There were large strain differences in all the measures collected, with at least a two-fold difference between strains with the lowest and the highest trait values Estimates of heritability ranged from 036 (spout side preference) to 087 (body weight) Body weight, food intake, and water intake were interrelated among the strains, although substantial strain variation in food and water intakes independent from body weight was present The strain differences described here provide useful information for designing mutagenesis screens and choosing strains for genetic mapping studies
585 citations
TL;DR: Results of a Monte Carlo study of exploratory factor analysis demonstrate that in studies characterized by low sample sizes the population factor structure can be adequately recovered if communalities are high, model error is low, and few factors are retained.
Abstract: Results of a Monte Carlo study of exploratory factor analysis demonstrate that in studies characterized by low sample sizes the population factor structure can be adequately recovered if communalities are high, model error is low, and few factors are retained. These are conditions likely to be encountered in behavior genetics research involving mean scores obtained from sets of inbred strains. Such studies are often characterized by a large number of measured variables relative to the number of strains used, highly reliable data, and high levels of communality. This combination of characteristics has special consequences for conducting factor analysis and interpreting results. Given that limitations on sample size are often unavoidable, it is recommended that researchers limit the number of expected factors as much as possible.
365 citations
TL;DR: The elucidation of the genotypes and phenotypes that result in excessive alcohol intake may lead to a better understanding of alcohol abuse and alcoholism and could guide strategies for potential treatment and prevention.
Abstract: The Indiana lines of selected rats, the HAD and LAD replicates and the P and NP lines, were bred for high and low alcohol preference. The P and HAD lines have met criteria for an animal model of alcoholism in that they voluntarily consume sufficient ethanol to achieve significant blood alcohol concentrations, and their alcohol-seeking behavior is reinforced by the pharmacological effects of ethanol rather than its taste, caloric content, or other properties. These lines have been characterized extensively for associated behavioral and physiological phenotypes. The P and HAD rats show an enhanced responsiveness to the stimulatory effects of ethanol and reduced sensitivity to the aversive sedative effects of ethanol. Consistent findings with the selected lines include differences in the mesolimbic dopamine reward system, as well as differences in serotonin, GABA, endogenous opioid, and neuropeptide Y systems. Genetic mapping studies have identified quantitative trait loci influencing alcohol preference on chromosomes 3, 4, and 8 in the inbred P/NP rats and on chromosomes 5, 10, 12, and 16 in the noninbred HAD1/LAD1 rats. The elucidation of the genotypes and phenotypes that result in excessive alcohol intake may lead to a better understanding of alcohol abuse and alcoholism and could guide strategies for potential treatment and prevention.
348 citations
TL;DR: HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans.
Abstract: In addition to their robust difference in trait anxiety, as illustrated by a variety of behavioral tests, HAB and LAB rats differ in their stress coping strategies, the former being more susceptible and vulnerable to stressor exposure and preferring more passive strategies. HAB rats of either gender show signs of a hyper-reactive hypothalamic-pituitary-adrenocortical (HPA) axis, thus resembling psychiatric patients. As shown by in situ hybridization and microdialysis in freely behaving animals, both the expression and release of vasopressin in the hypothalamic paraventricular nucleus are higher in HAB than in LAB rats, thus contributing to the HPA axis hyperdrive. Accordingly, in HAB animals, administration of a V1 receptor antagonist normalized the pathological outcome of the dexamethasone/corticotropin-releasing hormone test and triggered behavioral changes toward reduced anxiety and active stress coping. Pharmacological validation has revealed signs of depressive-like behavior, as HAB but not LAB rats have shown more active stress coping behavior and a normalized HPA axis after treatment with paroxetine. Of interest, this antidepressant reduced the hypothalamic overexpression of vasopressin; this novel mechanism of action is likely to contribute to paroxetine effects on both behavioral and neuroendocrine parameters. Cross-mating and cross-fostering paradigms showed that the divergent emotionality in HAB vs. LAB rats is determined genetically, rather than postnatally through maternal behavior. As the behavioral and neuroendocrine phenotyping pointed to the vasopressin gene as a candidate gene critically involved in anxiety, preliminary genetic approaches have been focused on this gene, revealing single nucleotide polymorphisms (SNPs) in the promotor area of the vasopressin gene in HAB, but not LAB rats. HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans.
267 citations
TL;DR: Genetic influences seem to be the main driving force behind continuity in general cognitive ability, represented by a common factor influencing FSIQ at all ages, and shared environmental influences are responsible for stability as well as change in the development of cognitive abilities.
Abstract: Measures of intelligence were collected in 209 twin pairs at 5, 7, 10, and 12 years of age, as part of a longitudinal project on intelligence, brain function, and behavioral problems. Intelligence was measured at 5, 7, and 10 years of age with the RAKIT, a well-known Dutch intelligence test, consisting of 6 subscales. At 12 years of age, the complete WISC-R was administered (12 subscales). Both intelligence tests resulted in a measure of full-scale IQ (FSIQ). Participation rate is around 93% at age 12. Correlation coefficients over time are high: (r(5-7) = .65; r(5-10) = .65; r(5-12) = .64; r(7-10) = .72; r(7-12) = .69 and r(10-12) = .78). Genetic analyses show significant heritabilities at all ages, with the expected increase of genetic influences and decrease of shared environmental influences over the years. Genetic influences seem to be the main driving force behind continuity in general cognitive ability, represented by a common factor influencing FSIQ at all ages. Shared environmental influences are responsible for stability as well as change in the development of cognitive abilities, represented by a common factor influencing FSIQ at all ages and age-specific influences, respectively.
211 citations
TL;DR: The heritability and prevalence of the gender identity disorder was examined, as well as its comorbidity with separation anxiety and depression, in a nonretrospective study of child and adolescent twins, supporting the hypothesis that there is a strong heritable component to GID.
Abstract: The heritability and prevalence of the gender identity disorder (GID) was examined, as well as its comorbidity with separation anxiety and depression, in a nonretrospective study of child and adolescent twins. The parents of 314 twins (ages 4–17 years; 96 monozygotic pairs [MZ] and 61 dizygotic [DZ] pairs) completed the Coolidge Personality and Neuropsychological Inventory (CPNI) containing a six-item DSM-IV-based GID scale. Prevalence of clinically significant GID symptomatology in the twin sample was estimated to be 2.3%. Univariate model fitting analyses were conducted using an ordinal transformation of the GID scale. The model that best described the data included a significant additive genetic component accounting for 62% of the variance and a nonshared environmental component accounting for the remaining 38% of the variance. Results suggested no heterogeneity in the parameter estimates resulting from age. The correlation between GID and depression was modest, but significant (r = .20; P .05). Overall, the results support the hypothesis that there is a strong heritable component to GID. The findings may also imply that gender identity may be much less a matter of choice and much more a matter of biology.
168 citations
TL;DR: The results suggest a trade-off between energy-demanding behavior and high production and that some of this may be caused by genetic linkage or pleiotropic gene effects.
Abstract: Behaviors with high energetic costs may decrease in frequency in domestic animals as a response to selection for increased production. The aim of this study was to quantify production traits, foraging behavior, and social motivation in F2 progeny from a White Leghorn x red junglefowl intercross (n = 751-1046) and to perform QTL analyses on the behavioral traits. A foraging-social maze was used for behavioral testing, which consisted of four identical arms and a central box. In two arms there was ad libitum access to the birds' usual food, and in the other two there was novel food (sunflower seeds) mixed with cat litter. In one arm with each of the two food sources, social stimuli were simulated by the presence of a mirror. Each bird could therefore feed on novel or well known food either alone or in the perceived company of a conspecific. Egg production, sexual maturity (females), food intake, and growth were measured individually, and residual food intake and metabolic body weight were estimated using standard methods. A genome scan using 104 microsatellite markers was carried out to identify QTLs affecting behavioral traits. Phenotypic growth rates at different ages showed weak associations in both sexes. Sexual maturity and egg weight were not strongly correlated to growth, indicating that these traits are not genetically linked. Time spent in each arm and in the central part of the maze was analyzed using principal component analyses. Four principal components (PC) were extracted, each reflecting a pattern of behavior in the maze. Females with early onset of sexual maturity scored higher on the PC1 reflecting preference for free food without social stimuli, and females with higher egg production scored higher on the PC2 reflecting exploration. Males with an overall higher growth rate and higher residual food intake scored higher on the PC3, which possibly reflected fear of the test situation, and tended to score higher on the PC4 reflecting low contrafreeloading. Significant QTLs were found for PC1 and PC4 scores on chromosomes 27 and 7, respectively. The location of the QTLs coincided with known QTLs for growth rate and body weight. The results suggest a trade-off between energy-demanding behavior and high production and that some of this may be caused by genetic linkage or pleiotropic gene effects.
147 citations
TL;DR: The present review will describe the formation of two pharmacologically selected lines of rats, their behavioral phenotypes, their responses to select drugs, their possible neurochemical correlates, and their use to detect the therapeutic potential of antidepressant drugs.
Abstract: The present review will describe the formation of two pharmacologically selected lines of rats, their behavioral phenotypes, their responses to select drugs, their possible neurochemical correlates, and their use to detect the therapeutic potential of antidepressant drugs The Flinders Line rats were established at Flinders University in Australia by selectively breeding for differential responses to an anticholinesterase agent from outbred Sprague-Dawley (SD) rats; the Flinders Sensitive Line (FSL) rats were more sensitive to the hypothermic and behavioral suppressing effects of this agent than the Flinders Resistant Line (FRL) rats The 8-OH-DPAT line rats were established at the University of North Carolina at Chapel Hill by selectively breeding for differential hypothermic responses to the 5-HT1A receptor agonist, 8-OH-DPAT; the high DPAT sensitive (HDS) line rats were more sensitive to the hypothermic effects of 8-OH-DPAT than the low DPAT sensitive (LDS) line rats Studies of these two pairs of lines have indicated that the FSL and HDS rats are both more susceptible to stress-induced behavioral disturbances Their usefulness in detecting potential antidepressant drugs and the relationship between mood disorders and drug abuse will be discussed
123 citations
TL;DR: The findings indicate that brain catecholamine loss decreases locomotor activity in the fly, as it does in mammals, and demonstrate the ability of functional genomic studies to mimic that of pharmacological inhibition of enzyme function or other similar processes.
Abstract: The brain of the adult fruit fly, Drosophila melanogaster, contains tyrosine hydroxylase, the rate-limiting enzyme required for catecholamine biosynthesis, as well as dopa decarboxylase. Catecholamines, principally dopamine, are also present. We have previously shown that pharmacological inhibition of tyrosine hydroxylase with α-methyl-p-tyrosine results in a dose-related inhibition of locomotor activity in adult organisms. Similar results were found with reserpine, a well-known inhibitor of catecholamine uptake into storage granules. The drug-induced inhibition could be prevented in each case by the concomitant administration of l-dopa. The single-copy gene coding for tyrosine hydroxylase in Drosophila is pale (ple). Both null and temperature-sensitive loss of function mutant alleles of ple are recessive embryonic lethals. Heterozygous null mutant flies have normal locomotor activity demonstrating that only a single dose of the wild type form of ple is required to support normal function. Both hemizygous and homozygous temperature-sensitive ple mutants (plets1) also show normal locomotor activity at the permissive temperature for this mutant allele (18°C), which progressively declines as the temperature is increased to its restrictive level (29°C). These abnormal locomotor effects are reversible by l-dopa. Thus the effects on locomotor activity resulting from the pharmacological inhibition of catecholamine synthesis or storage are the same as those resulting from lack of tyrosine hydroxylase expression. These findings indicate that brain catecholamine loss decreases locomotor activity in the fly, as it does in mammals, and demonstrate the ability of functional genomic studies to mimic that of pharmacological inhibition of enzyme function or other similar processes.
111 citations
TL;DR: It is shown that APO-SUS rats share a large number of behavioral, neurochemical, endocrinological, and immunological similarities with patients suffering from schizophrenia, and might represent a promising animal model for studying this severe mental disorder.
Abstract: Many years ago we found a bimodal distribution of a number of different behaviors in our regular outbred Wistar stock. This was observed in the response to novelty, the response in a resident-intruder test as well as in the stereotypy response to the dopamine agonist apomorphine. On the basis of that, we decided to selectively breed these animals, which resulted in the the APO-SUS and APO-UNSUS lines. The APO-SUS rats show a strong, stereotyped gnawing response, whereas APO-UNSUS show only a weak gnawing response. Follow-up studies have shown that the phenotypical expression of these rats depend on genetic and early and late environmental factors. Because these rats were not selected on the basis of a specific behavioral trait, but rather on the basis of a difference in susceptibility for a specific neurotransmitter, it is not surprising that these animals show major differences in the neurochemical state of the central nervous system. In fact, in many respects they represent mirror images of each other. Moreover, these animals show clear differences in their endocrine and immunological systems. APO-SUS rats can be characterized as having a hyper-reactive hypothalamus-pituitary-adrenal axis, and a dominance of the TH2 system. Apart from discussing the main differences between APO-SUS and APO-UNSUS rats, the review specifically focuses on the former as a potential model for schizophrenia. We have been able to show that APO-SUS rats indeed share a large number of behavioral, neurochemical, endocrinological, and immunological similarities with patients suffering from schizophrenia. Because schizophrenia is also likely to result from an interaction between genetic and early stressful life events, the APO-SUS rat might represent a promising animal model for studying this severe mental disorder.
107 citations
TL;DR: Simulation indicated that the use of AIC to determine the “best” univariate model for a discrete trait tended to yield the incorrect model rather frequently, and the parameter estimates of the ‘best’ model by AIC were biased sharply upward as were the associated 95% confidence intervals.
Abstract: Akiake's Information Criterion (AIC) is commonly used in univariate twin modeling of a discrete trait to prune a full model into a more parsimonious submodel. It is possible that this practice could introduce bias and inaccuracy, and we could identify no prior systematic study of these issues. Thus, we used simulation to investigate the performance of AIC-guided modeling across a broad range of parameters. Our simulations indicated that the use of the AIC to determine the "best" univariate model for a discrete trait tended to yield the incorrect model rather frequently. Moreover the parameter estimates of the "best" model by AIC were biased sharply upward as were the associated 95% confidence intervals. These results suggest that the use of AIC to guide twin modeling for univariate discrete traits should either be abandoned or used with great caution.
TL;DR: The question of how a genetic hierarchical model fits the Wechsler Adult Intelligence Scale (WAIS) subtests and the Raven Standard Progressive test score and the covariation among the WAIS group factors is addressed and strongly support the notion of a biological basis of g.
Abstract: Hierarchical models of intelligence are highly informative and widely accepted. Application of these models to twin data, however, is sparse. This paper addresses the question of how a genetic hierarchical model fits the Wechsler Adult Intelligence Scale (WAIS) subtests and the Raven Standard Progressive test score, collected in 194 18-year-old Dutch twin pairs. We investigated whether first-order group factors possess genetic and environmental variance independent of the higher-order general factor and whether the hierarchical structure is significant for all sources of variance. A hierarchical model with the 3 Cohen group-factors (verbal comprehension, perceptual organisation and freedom-from-distractibility) and a higher-order g factor showed the best fit to the phenotypic data and to additive genetic influences (A), whereas the unique environmental source of variance (E) could be modeled by a single general factor and specifics. There was no evidence for common environmental influences. The covariation among the WAIS group factors and the covariation between the group factors and the Raven is predominantly influenced by a second-order genetic factor and strongly support the notion of a biological basis of g.
TL;DR: The mixed or multilevel model is proposed as an alternative approach to existing behavior genetic analysis—an alternative to correlation analysis, the DeFries-Fulker analysis, and structural equation modeling, and analysis of the possible genetic basis for friendship selection.
Abstract: We propose the mixed model or multilevel model as a general alternative approach to existing behavior genetic analysis—an alternative to correlation analysis, the DeFries-Fulker analysis, and structural equation modeling. The mixed or multilevel model handles readily families of behavioral genetic data, which include paired sibling data (e.g., pairs of MZ and DZ twins) and clustered sibling data (e.g., a family of more than two biological siblings) as special cases. Not only can a family of behavioral genetic data have more than two siblings, it can also contain multiple types of siblings (e.g., a pair of MZ twins, a pair of DZ twins, a full sibling, and a half sibling). In contrast to the traditional approaches, the mixed or multilevel model is insensitive to the order of the siblings in a sibling cluster. We apply our approach to a large, nationally representative behavior genetic sample collected recently by the Add Health Study. We demonstrate the approach through several applications using both clustered and family complex behavioral genetic data: conventional variance decomposition analysis, analysis of interactions between genetic and environmental influences, and analysis of the possible genetic basis for friendship selection. We compare results from the mixed or multilevel model, Pearson's correlation analysis, and the structural equation model.
TL;DR: The case-control approach may prove to be more economical and expeditious than the TDT design for diseases in which the cost and time required to collect simplex families is much greater than that needed to acquire isolated disease cases.
Abstract: Sample size required for the TDT and the case-control designs was studied for marker-based genome-wide scans for disease association. The influence of various parameters on sample size required to attain a given level of power was analyzed in detail. Small genotypic relative risks, low levels of linkage disequilibrium, and departure from equal frequencies for the disease allele and associated marker allele, significantly and similarly increase sample size required by either the TDT or case-control design. Under the case-control paradigm, we show that the optimal strategy will often be to collect many more control individuals than disease cases with the optimal ratio depending on the relative cost of acquiring cases as compared to controls. For the TDT, the number of required simplex families is virtually equal to the number of cases required for similar power in case-control studies with an equal number of cases and controls. The case-control approach may therefore prove to be more economical and expeditious than the TDT design for diseases in which the cost and time required to collect simplex families is much greater than that needed to acquire isolated disease cases. Nevertheless, possible population stratification needs to be addressed when the case-control design is applied.
TL;DR: It has been found that alterations in the peripheral sympathetic nervous system (PSNS) are correlated with strain differences in open-field defecation (OFD) in the Maudsley model, and it has been proposed that the lower OFD of MNRA/Har rats is a direct result of sympathetic inhibition of colonic motility.
Abstract: Research on the Maudsley Reactive and Maudsley Nonreactive strains conducted primarily between 1980 and 2001 is reviewed. One line of research, which has found consistent differences between the Harrington derivation of the Maudsley Reactive (MR/Har) and Maudsley Nonreactive (MNRA/Har) strains in conflict situations, appears to support the traditional view of the two strains as representing models of global differences in emotionality. In contrast, comparisons of the two strains in two commonly used tests that involve a component of fear either do not reveal differences between the strains (escape-avoidance conditioning) or are inconsistent in expression (elevated plus maze). Emphasis is placed on the importance of recognizing that most of the phenotypic differences discovered among selected inbred strains, including the Maudsleys, will inevitably be unrelated to the original selection criterion, but that many of these phenotypic differences will have their own intrinsic interest. For example, the fact that, relative to MNRA/Har, two bottle ethanol preference is greater in MR/Har rats and that MR/Har rats exhibit greater exploration of novel stimuli when these are presented in a familiar environment may have little to do with the hypothesized differences in emotionality among the strains. It is suggested the MR/Har drinking pattern in alcohol preference tests, which is characterized by considerable variability, may complement other models of alcoholism, especially in the investigation of environmental influences which contribute to the variability. In the case of strain differences in response to novelty, this may help explain some of the inconsistencies in findings in the elevated plus maze, which, aside from provoking fear, also contains an important element of novelty. Finally, it has been found that alterations in the peripheral sympathetic nervous system (PSNS) are correlated with strain differences in open-field defecation (OFD) in the Maudsley model, and it has been proposed that the lower OFD of MNRA/Har rats is a direct result of sympathetic inhibition of colonic motility. These strain differences in the PSNS are furthermore associated with important alterations in the response of the central noradrenergic system to acute and chronic stress. It is hypothesized that genes may have influenced PSNS tone by altering CNS structures with descending projections. If the link between low levels of OFD and higher peripheral sympathetic tone is supported by additional experiments, this will force reconsideration of OFD as an index of emotionality.
TL;DR: The associations among the responses to different minerals were only modest, suggesting distinct genetic controls of sodium, potassium, calcium, and ammonium consumption.
Abstract: Male mice from 28 inbred strains (129P3/J, A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57L/J, CAST/Ei, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/H1J, LP/J, NOD/LtJ, NZB/B1NJ, P/J, PL/J, RBF/DnJ, RF/J, RIIIS/J, SEA/GnJ, SJL/J, SM/J, SPRET/Ei, and SWR/J) were tested with NaCl (75–450 mM), KCl (30–300 mM), CaCl2 (3–100 mM), and NH4Cl (10–300 mM) solutions using two-bottle preference tests with water as the second choice. For each mineral, there was a wide range of strain variation in solution intakes and preferences. This variation had a substantial genetic component as assessed using heritability estimates. In most cases, the strain means were continuously distributed; however, strains with deviating high or low intakes or preferences were also observed. The associations among the responses to different minerals were only modest, suggesting distinct genetic controls of sodium, potassium, calcium, and ammonium consumption. These results provide a valuable resource for investigators who wish to identify genes involved in the regulation of mineral consumption and balance.
TL;DR: The hypothesis that genetic dominance influences the defensive behavior of honeybees is supported and the effect of sting1 on the defensiveness of individual worker bees is confirmed.
Abstract: The stinging and guarding components of the defensive behavior of European, Africanized, hybrid, and backcross honeybees (Apis mellifera L.) were compared and analyzed at both colony and individual levels. Hybrid and Africanized backcross colonies stung as many times as Africanized ones. European backcross colonies stung more than European bees but not as many times as Africanized or Africanized backcross colonies. The degree of dominance for the number of times that worker bees stung a leather patch was estimated to be 84.3%, 200.8%, and 145.8% for hybrid, backcross European, and backcross Africanized colonies, respectively. Additionally, both guards at the colony entrance and fast-stinging workers of one European backcross colony had a significantly higher frequency of an Africanized DNA marker allele, located near "sting1," a QTL previously implicated in stinging behavior at the colony level. However, guards and fast-stinging bees from a backcross to the Africanized parental colony did not differ from control bees in their frequency for the Africanized and European markers, as would be expected if large genetic dominance effects for sting1 exist. These results support the hypothesis that genetic dominance influences the defensive behavior of honeybees and confirm the effect of sting1 on the defensiveness of individual worker bees.
TL;DR: The evidence gathered so far supports a hyperfunctioning mesocorticolimbic system that makes NHE rats a useful tool for the study of hyperactivity and attention deficit, learning and memory disabilities, and drug abuse.
Abstract: The Naples High- (NHE) and Low-Excitability (NLE) rat lines have been selected since 1976 on the basis of behavioral arousal to novelty (Lat-maze). Selective breeding has been conducted under continuous genetic pressure, with no brother-sister mating. The behavioral analyses presented here deal with (1) activity in environments of different complexity, i.e., holeboard and Lat maze; (2) maze learning in hexagonal tunnel, Olton, and Morris water mazes and; (3) two-way active avoidance and conditioned taste aversion tests. Morphometric analyses deal with central dopaminergic systems at their origin and target sites, as well as the density of dopamine transporter immunoreactivity. Molecular biology analyses are also presented, dealing with recent experiments on the prefrontal cortex (PFc), cloning and identifying differentially expressed genes using subtractive libraries and RNAase protection. The divergence between NLE and NHE rats varies as a function of the complexity level of the environment, with an impaired working and reference memory in both lines compared to random bred (NRB) controls. Moreover, data from the PFc of NHE rats show a hyperdopaminergic innervation, with overexpression of mRNA species involved in basal metabolism, and down-regulation of dopamine D1 receptors. Altogether, the evidence gathered so far supports a hyperfunctioning mesocorticolimbic system that makes NHE rats a useful tool for the study of hyperactivity and attention deficit, learning and memory disabilities, and drug abuse.
TL;DR: The ALDH2*2 allele, detected in nearly half of the subjects, showed an overwhelming protective effect against a high level of alcohol consumption and problem drinking behavior, as determined by the Kurihama Alcoholism Screening Test (KAST).
Abstract: Among ethanol-metabolizing enzymes, the ALDH2*2 allele, ADH2*2 allele, and c2 allele of the cytochrome P450-2E1 (CYP2E1) gene are unique to Orientals. This prompted us to analyze their contribution to drinking behavior in 322 middle-aged Japanese men. The ALDH2*2 allele, detected in nearly half of the subjects, showed an overwhelming protective effect against a high level of alcohol consumption and problem drinking behavior, as determined by the Kurihama Alcoholism Screening Test (KAST). The ADH2*2 allele, in 95% of the subjects, exhibited an additive suppressive effect on alcohol consumption, whereas the c2 allele of CYP2E1, in 40% of the subjects, was associated with greater alcohol consumption. Problem drinkers showing a KAST score of 2.0 or higher were frequent among the few subjects with the ADH2*1/1 genotype, but not in the large number of subjects having the c2 allele of CYP2E1. These findings may explain, at least in part, why in Japan the number of alcoholic patients is small relative to the number of heavy drinkers.
TL;DR: It is indicated that reading and language deficits are significantly heritable and that differential genetic influences as a function of IQ are evident for measures of word recognition and phonological decoding.
Abstract: Results obtained from previous studies of word recognition, reading component skills, and reading composite measures suggest that genetic factors may be more important as a cause for reading disability among children with higher IQ scores than among those with lower IQ scores. To investigate the genetic etiology of reading disability further, measures of word recognition, phonological decoding, orthographic coding, and phoneme awareness were obtained from a total of 465 twin pairs with a positive school history of reading problems. The basic and extended DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data were employed to investigate the etiology of group deficits in reading and language skills, as well as to assess differential genetic etiology for the reading-related measures as a function of IQ. Data from 168 sibling pairs (drawn from the twins' families), including fraternal twin pairs and their siblings, as well as non-twin siblings of identical twins were subjected to single-marker analyses using the DF basic linkage model to examine evidence for linkage of a quantitative-trait locus (QTL) for reading and language deficits to the short arm of chromosome 6. Lastly, to investigate the possible differential influence of this QTL as a function of IQ, the sibling pair data were fitted to an extension of the DF basic linkage model. Results indicated that reading and language deficits are significantly heritable and that differential genetic influences as a function of IQ are evident for measures of word recognition and phonological decoding. Results obtained from linkage analyses confirmed the presence of a QTL on chromosome 6p that influences phonological and orthographic skills, as well as phoneme awareness measures, and suggest that this QTL may influence phoneme awareness differentially as a function of IQ: however, future analyses with considerably larger samples are needed to test the hypothesis of differential QTL influence more rigorously.
TL;DR: Compared the rates of ultrasonic calling of infant mice of two genotypes in two situations, cold and rotation, to understand the roles of the stimuli and genotypes employed and the effects of pharmacological agents on infant mice.
Abstract: There has been a revival of interest recently in the ultrasonic calls of infant rodents as investigators are using them to assess neurobehavioral development and animal models of anxiety. We compared the rates of ultrasonic calling of infant mice of two genotypes in two situations, cold and rotation. The subjects of study were 169 mouse pups from 29 litters and of two F1 genotypes, C57BL/10J × DBA/2J and C57BL/10J × SJL/J. Half of each litter was recorded in a cool situation for 20 seconds and the other half was recorded while rotating at 10 rpm for 20 seconds. All pups were recorded on days of age 2 to 8. Rotation elicited calling at about twice the rate as cool temperature on each day of age and on average across days; situation (cold or rotation) accounted for over 50% of the variation between litters. Genotype also altered call rate, and on some days situation and genotype interacted. In studies of neurobehavioral development and the effects of pharmacological agents on infant mice, it is particularly important to understand the roles of the stimuli and genotypes employed.
TL;DR: Investigation of whether performance on the Matching Familiar Figures Test (MFFT) and Continuous Performance Task (CPT) is genetically influenced in childhood finds that MZ twins perform more similarly than DZ twins on the MFFT, but not the CPT.
Abstract: There has been much interest in the genetics of attention deficit hyperactivity disorder and molecular genetic studies are now underway. The success of genetic studies will depend on how well the phenotype is defined. Twin studies using parent and teacher rated questionnaires or interviews all appear to yield highly heritable measures. Nevertheless, there is evidence to suggest that parent measures are subject to rater bias. Consequently there has been much interest in obtaining more objective measures of related traits such as attention span and impulsiveness using, computerised neuropsychological tasks. However there have been few twin studies examining the genetic contribution to these neuropsychological measures. The present study aims to investigate whether performance on the Matching Familiar Figures Test (MFFT) and Continuous Performance Task (CPT) is genetically influenced in childhood. 20 monozygotic (MZ) and 20 dizygotic (DZ) twin pairs were randomly selected from the Greater Manchester Twin Register. Preliminary data suggest that MZ twins perform more similarly than DZ twins on the MFFT, but not the CPT. Future work needs to examine whether other neuropsychological measures commonly used in research on ADHD are genetically influenced using larger twin samples.
TL;DR: It is suggested that strains differentially use or retain information, gathered from the initial exposure, to avoid the open quadrants on subsequent exposure to the maze.
Abstract: We recently tested three inbred mouse strains (C57BL/6J, DBA/2J, C3H/HeJ) and two F1 hybrids (B6C3F1/J, C3D2F1/J) in an elevated zero-maze for 3 consecutive days. As measured by the latency to enter an open quadrant and percentage of time spent in the open, anxiety increased over the three trials. Furthermore, we observed that some strains used visual cues to avoid the open arms of the zero-maze on the initial exposure, while other strains may have used other sensory cues. These results suggest that strains differentially use or retain information, gathered from the initial exposure, to avoid the open quadrants on subsequent exposure to the maze. Moreover, this repeated trial test may more accurately reflect anxiety in strains that are visually impaired.
TL;DR: Performance during training indicated that RHA/Verh rats showed less differentiated behavior between odd and even trials, indicating a relative working memory deficit at advanced ages in that rat line.
Abstract: The present study explored the effects of infantile stimulation (i.e., neonatal handling or NH) on the performance of 18-month-old Roman high-avoidance (RHA/Verh) and low-avoidance (RLA/Verh) rats in a swimming pool matching-to-place (SPMP) test. This test (also called repeated acquisition and place learning-set paradigm) consists of administering pairs of consecutive trials in the Morris water maze. The difference between each “odd” and the consecutive “even” trial of a trial pair is considered to be a measure of working memory. The same rats were first tested for exploration and novelty-seeking in a hole-board test in the presence of novel objects, which showed that RHA/Verh rats were more explorative than their RLA/Verh counterparts, and that NH treatment augmented exploration in RLA/Verh rats, generally eliminating the genetically-based differences between the lines. RHA/Verh rats performed less efficiently than RLA/Verh rats in the SPMP test, and NH facilitated acquisition in the early stages of training in both rat lines, an effect that was presumably due to an improvement in the acquisition of spatial reference information. Performance during training also indicated that RHA/Verh rats showed less differentiated behavior between odd and even trials, indicating a relative working memory deficit at advanced ages in that rat line.
TL;DR: In this paper, the authors found that EC-SOD overexpressing mice had significantly better choice accuracy than the control mice (p < 0.005) on the 8-arm radial maze over 21 sessions of training.
Abstract: Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide and appears to play a role in controlling oxidative stress and intercellular signaling. Whether EC-SOD overexpression would help or hinder neurobehavioral function appears to depend on the age of the individual. In young adult mice, we have found that EC-SOD overexpression can interfere with learning on the radial-arm maze, possibly by reducing control over nitric oxide neurotransmission. In aged mice, we found, in the current study, that EC-SOD overexpression greatly improves learning on the radial-arm maze. Control (N = 17) and EC-SOD overexpressing mice (N = 13) acquired the 8-arm radial maze over 21 sessions of training. The EC-SOD overexpressing mice had significantly better choice accuracy than the control mice (p < 0.005). The EC-SOD overexpressing mice averaged 6.34 ± 0.22 correct arm entries before an error (entries to repeat) during the acquisition phase, while the control mice averaged 5.18 ± 0.22 entries to repeat. EC-SOD genotype did not cause a main effect on response latency. The advantage held by the EC-SOD overexpressing mice persisted during the eight-session post-acquisition phase of testing (p < 0.01). When there was a shift from high to low levels of motivation by reducing the period of food restriction before testing, the EC-SOD overexpression-induced improvement was reduced slightly, but it was still significant compared with the wild-type controls (p < 0.025). Then, after 4 months of no testing, the mice were tested for retention and reacquisition of performance on the radial-arm maze. The EC-SOD overexpressing mice maintained their significantly better choice accuracy (p < 0.05). Enhancement of EC-SOD activity appears to improve learning and memory performance, specifically in aging mice. EC-SOD mimetic treatment during the course of aging may hold promise for aging-induced cognitive impairment.
TL;DR: A model with observed and latent variables that does not impose restrictions on the number of variables or the direction of their causal relations and provides a general approach for fitting structural equation models to empirical data is proposed.
Abstract: The etiology of complex traits may perhaps best be conceptualized by an interplay of multiple factors that mediate the influence of the genes on the eventual outcome. The possibilities of studying aspects of this interplay using existing methods are generally limited. We therefore propose a model with observed and latent variables that does not impose restrictions on the number of variables or the direction of their causal relations and provides a general approach for fitting structural equation models to empirical data. The model is very flexible and (1) allows for genetic effects on the means, variances, and relations between variables, (2) can control for stratification effects on all these components, (3) can be fitted in nuclear families of any size, (4) is estimated using an interpretable parameterization, and (5) can incorporate di- and multi-allelic loci, marker haplotypes, multiple loci simultaneously, and parental genotypes. We indicate how the model can be estimated with the Mx software (Neale et al., 1999) and have written a program to enable geneticists who are not acquainted with Mx to fit their own submodels in a simple and efficient way. A simulation study showed that the model yielded correct Type I errors, unbiased parameter estimates, and satisfactory power to discriminate between alternative models. An example is also given that illustrates how the model could be applied to real data.
TL;DR: A wide genome scan was performed to map the QTLs that control various aspects of the performance, using the RI strain methodology and confirmed previous data showing that the escape latencies and the spatial bias rely on two distinct components of the task, controlled by different loci.
Abstract: The Morris navigation task is widely used to study spatial abilities in rodents; namely, to analyze the effects of mutations in genetically engineered mice. Although quantitative and Mendelian genetic studies have shown that the variation of these abilities is partly under genetic control, little is known about these genetic factors. In order to analyze the genetic architecture of spatial navigation in mice, a wide genome scan was performed to map the QTLs that control various aspects of the performance, using the RI strain methodology. Latencies to locate the submerged platform across learning sessions and performance to the spatial probe test were analyzed in the 26 strains of the B × D RI series. Both cluster analysis of behavioral measurements and QTL mapping confirmed previous data showing that the escape latencies and the spatial bias rely on two distinct components of the task, controlled by different loci. A QTL on chromosome 1 influenced escape latencies during the four training sessions, whereas another QTL, located on chromosome 5, was shown to control spatial performance at the probe trial and also exhibited epistatic interactions with two other QTLs on chromosomes 2 and 13. The function of these QTLs is examined in the broader context of hippocampal-dependent learning processes and in relation to QTLs already found in similar positions in other behavioral traits.
TL;DR: A genome screen using F2 animals with extreme saccharin or alcohol consumption to identify QTLs contributing to saccharine-related phenotypes in the rat is performed and results provide the first results of a genome screen for QTL's contributing to Saccharin- related phenotypes.
Abstract: The inbred preferring (iP) and nonpreferring (iNP) rat strains were derived from the selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines. Previously, 381 iP × iNP F2 progeny were generated to identify quantitative trait loci (QTLs) influencing alcohol consumption and preference. Saccharin consumption (ml/48 h) and saccharin intake (ml/kg/day) were also measured in the F2 sample and were significantly correlated with both alcohol consumption and preference (all r ≥ .20, p < .0001), suggesting that there might be some QTLs influencing both saccharin and alcohol phenotypes. We have performed a genome screen using F2 animals with extreme saccharin or alcohol consumption to identify QTLs contributing to saccharin-related phenotypes. Lod scores greater than 2.0 were found on chromosomes 3, 16 and 18 in this sample. Additional genotyping was performed in these regions in the full sample of 381 F2 progeny to further characterize these putative QTLs. On chromosome 3, the maximum lod score in the full sample was 2.7 with saccharin consumption. This QTL appears to overlap with a QTL identified for alcohol consumption in the iP and iNP lines and has pleiotropic effects on both phenotypes. Interestingly, this region of rat chromosome 3 is syntenic with mouse chromosome 2, where a QTL influencing alcohol preference has been previously reported. The QTL on chromosome 16 has a maximum lod score of 4.0 with saccharin intake and 2.6 with saccharin consumption. The QTL on chromosome 18 has a maximum lod score of 2.7 with saccharin consumption. Taken together, these data provide the first results of a genome screen for QTLs contributing to saccharin phenotypes in the rat.
TL;DR: It is found that the flies' geographic origin affects emigration behavior (flies from a relatively closed natural system seem to display lower emigration ability than those from an open habitat), although broader sampling from various habitats is needed to confirm these results.
Abstract: Evolutionary biology considers migration behavior as central in genetic structure of populations and speciation. Here we report on emigration patterns in Drosophila melanogaster behavior under laboratory conditions. For this study, a special apparatus was employed that includes a few important changes in its design and size compared with other known systems. The results presented in this paper were obtained on flies derived from natural populations of two contrasting climatic and geographical regions, from mesic northern and xeric southern parts of Israel. Highly significant difference between sexes in emigration activity was found for both localities. Emigration activity of females appeared to be higher than that of males. We also found that the flies' geographic origin affects emigration behavior (flies from a relatively closed natural system seem to display lower emigration ability than those from an open habitat), although broader sampling from various habitats is needed to confirm these results.
TL;DR: In the current study, the authors searched for quantitative trait loci (QTL) responsible for a conditioned taste aversion (CTA) measured as a decrease in the intake of a saccharin conditioned stimulus followed by an i.p. injection of LiCl.
Abstract: In the current study, we searched for quantitative trait loci (QTL) responsible for a conditioned taste aversion (CTA) measured as a decrease in the intake of a saccharin conditioned stimulus followed by an ip injection of 015 M LiCl (lithium chloride) (2 ml/100 g body weight) A genome scanning for QTL associated with CTA was performed in the HXB/BXH sets of recombinant inbred (RI) strains derived from the Brown Norway (BN-Lx) rat and the spontaneously hypertensive rat (SHR) The BN-Lx progenitor showed a significantly stronger CTA (83 ± 28%) than the SHR progenitor (278 ± 33%, p < 0001) The distribution of CTA values among RI strains was continuous, suggesting a polygenic mode of inheritance Genome scanning of RI strains with more than 700 gene markers revealed a significant association of CTA with the D2Cebr11s4 marker on chromosome 2 (LRS = 227) and with the D4Cebrp149s8 marker on chromosome 4 (LRS = 234) The chromosome 2 putative QTL was confirmed by detecting a significant difference in CTA between the SHR progenitor (278 ± 33%) and the SHR-2 (SHRBN-D2Rat171/D2Arb24) congenic strain (131 ± 44%, p < 01) that are genetically identical except for a segment of chromosome 2 that was transferred onto the genetic background of the SHR from the BN strain