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Temperature-sensitive paralytic mutants are enriched for those causing neurodegeneration in Drosophila.

Age-dependent neurodegeneration is a pathological condition found in many metazoans. Despite the biological and medical significance of this condition, the cellular and molecular mechanisms underlying neurodegeneration are poorly understood. The availability of a large collection of mutants exhibiting neurodegeneration will provide a valuable resource to elucidate these mechanisms. We have developed an effective screen for isolating neurodegeneration mutants in Drosophila. This screen is based on the observation that neuronal dysfunction, which leads to observable behavioral phenotypes, is often associated with neurodegeneration. Thus, we used a secondary histological screen to examine a collection of mutants originally isolated on the basis of conditional paralytic phenotypes. Using this strategy, we have identified 15 mutations affecting at least nine loci that cause gross neurodegenerative pathology. Here, we present a genetic, behavioral, and anatomical analysis of vacuous (vacu), the first of these mutants to be characterized, and an overview of other mutants isolated in the screen. vacu is a recessive mutation located cytologically at 85D-E that causes locomotor defects in both larvae and adults as well as neuronal hyperactivity. In addition, vacu exhibits extensive age-dependent neurodegeneration throughout the central nervous system. We also identified mutations in at least eight other loci that showed significant levels of neurodegeneration with a diverse array of neuropathological phenotypes. These results demonstrate the effectiveness of our screen in identifying mutations causing neurodegeneration. Further studies of vacu and the other neurodegenerative mutants isolated should ultimately help dissect the biochemical pathways leading to neurodegeneration.

Animals↗

Genetic and environmental influences on the continuous scales of the Myers-Briggs Type Indicator: an analysis based on twins reared apart.

The Myers-Briggs Type Indicator was administered to a sample of 61 monozygotic twins reared apart (MZA), 49 dizygotic twins reared apart (DZA), and 92 spouses, who participated in the Minnesota Study of Twins Reared Apart (MISTRA) from 1979 to 1995. Twins' scores on the continuous scales were subjected to behavior genetic model-fitting procedures. Extraversion-Introversion and Thinking-Feeling yielded heritabilities of about .60, consisting largely of nonadditive genetic variance. Sensing-Intuition and Judgment-Perception yielded heritabilities of about .40, consisting largely of additive genetic variance. Spouse correlations for three of the four scales were near zero and not statistically significant; one spouse correlation (Sensing-Intuition) was modestly positive and statistically significant.

Adult↗

Using genetic analyses to clarify the distinction between depressive and anxious symptoms in children.

Self-report measures of depression and anxiety in children are highly correlated and distinguishing between shared and independent factors in their etiologies is therefore problematic. The aim of this article was to test whether less correlated measures of depression and anxiety could be produced and, if so, what genetic and environmental factors would account for the variance in these symptoms. Second-order factor analysis of the items from two standardized self-report questionnaires of depression and anxiety collected from 395 pairs of same-sex twins aged 8 to 16 years resulted in purer dimensions of depression and anxiety. Behavioral genetic analyses confirmed the distinction between these two dimensions, and bivariate analyses revealed that the association between the two was primarily accounted for by shared genetic factors.

Adolescent↗

The genetic analysis of a uniquely dose-sensitive chromosomal region of Drosophila melanogaster.

In their extensive analysis of the effects of segmental aneuploidy on development to the adult stage, LINDSLEY and SANDLER et al. (1972) identified salivary chromosome region 83D-E as apparently uniquely dose-sensitive. Neither the hypoploid nor hyperploid classes appeared to survive to the adult stage, although segmental hyperploidy of all other regions of the genome is compatible with normal or quasi-normal development. In the present investigation, this genetic behavior is shown to be a concomitant of region 83D-E itself, and independent of the particular Y-autosome translocations utilized to generate aneuploid classes. Newly induced chromosomal duplications including 83D-E are recovered by their ability to complement the corresponding deficiency; these aberrations indicate that the phenomenon depends on genetic dosage per se and is independent of linkage relationships. Further tests involving the generation of large numbers of aneuploid zygotes support the conclusion that these individuals very rarely and possibly never survive to the adult stage. Finally, crosses yielding hypertriploid females and intersexes indicate that these aneuploids often survive and, in the former case, are fertile. No viable hypotriploid female or intersex was recovered.

Aneuploidy↗

Does father absence place daughters at special risk for early sexual activity and teenage pregnancy?

The impact of father absence on early sexual activity and teenage pregnancy was investigated in longitudinal studies in the United States (N = 242) and New Zealand (N = 520), in which community samples of girls were followed prospectively from early in life (5 years) to approximately age 18. Greater exposure to father absence was strongly associated with elevated risk for early sexual activity and adolescent pregnancy. This elevated risk was either not explained (in the US. study) or only partly explained (in the New Zealand study) by familial, ecological, and personal disadvantages associated with father absence. After controlling for covariates, there was stronger and more consistent evidence of effects of father absence on early sexual activity and teenage pregnancy than on other behavioral or mental health problems or academic achievement. Effects of father absence are discussed in terms of life-course adversity, evolutionary psychology, social learning, and behavior genetic models.

Adolescent↗

Multiple raters of disruptive child behavior: using a genetic strategy to examine shared views and bias.

Most research on child behavior incorporates information from different individuals. While agreement between informants is generally only modest, there is little understanding of the processes underlying disagreement. In twin studies, differential agreement among raters for MZ and DZ twins is of particular concern. The processes underlying differences among mother, father, and child ratings of oppositional and conduct disorder symptoms are explored. Evidence in favor of a shared parental view of behavior is presented. Parental ratings give higher intrapair correlations, which could be due to either parents rating their twins more similarly or twins contrasting themselves. Rater bias and situational specificity are among the possible explanations of differential ratings. The effects of incorporating multiple raters of behavior on estimates of genetic and environmental effects are explored. These suggest that genetic influences are greater for the shared (multiple-rater) phenotype than for individual ratings; reduction in measurement error is only a partial explanation.

Adolescent↗

[The role of brain serotonin in the expression of genetically determined defensive behavior].

The review summarizes the results of long-term studies on the role of the brain mediator serotonin and genetic predisposition to various types of defensive behavior. The involvement of the serotonergic brain system in the mechanisms of genetic control of both active and passive defensive responses has been established using silver foxes, Norway rats of S40 selection for low and high aggressiveness to humans, aggressive mice with genetic knockout of monoaminoxidase A, and S40 rats selected for predisposition to passive defensive response of freezing (catalepsy). The changes in the serotonergic 5-HT1A-brain receptors of rats genetically predisposed to different strategies of defensive behavior were similar. However, the activity of the key enzyme of serotonin biosynthesis and the brain structures, in which serotonin metabolism was altered, significantly differed with regard to the preferred strategy. The conclusion was drawn that the 5-HT1A-receptors and enzymes of serotonin metabolism in the brain are involved in implementing genetic control of defensive behavior. Expression of the 5-HT1A-brain receptors was suggested to determine the levels of fear and anxiety and, consequently, the predisposition to defensive behavior, whereas the preferred strategy of defensive response (active or passive defensive) depends on genetically determined features of serotonin metabolism in the brain structures.

Animals↗

Sociogenomics: social life in molecular terms.

Spectacular progress in molecular biology, genome-sequencing projects and genomics makes this an appropriate time to attempt a comprehensive understanding of the molecular basis of social life. Promising results have already been obtained in identifying genes that influence animal social behaviour and genes that are implicated in social evolution. These findings - derived from an eclectic mix of species that show varying levels of sociality - provide the foundation for the integration of molecular biology, genomics, neuroscience, behavioural biology and evolutionary biology that is necessary for this endeavour.

Animals↗

[Food search by mice solving an extrapolation problem after suppression of smell by zinc sulfate].

Anosmia induced by intranasal zinc administration to mice capable of solving an extrapolation problem (search for food which disappears from animal sight in definite direction), led to disturbance of normal food searching behaviour. In anosmic mice the percentage of task solutions (correct as well as incorrect) in which the trajectory was the shortest ("goal-directed"), was significantly lower than in controls. At the same time the percentages of correct "goal-directed" choices were equal in both groups. The main differences in the number of correct task solutions were among those trials in which non-goal-directed behaviour was delivered. Thus zinc induced anosmia provokes rather severe deteriorations of food searching behaviour. The investigated group of mice possessing Robertsonian translocation Rb(8, 17) 1 IEM, reveals no disturbance of extrapolation capacity during first 20 s after task presentation. This signifies that this capacity which in this group is higher than in other mice, is not determined by peculiarities of their olfaction.

Animals↗

Doublesex gene expression in the central nervous system of Drosophila melanogaster.

Despite several behavior-genetic studies that have suggested roles played by doublesex (dsx) in neural tissues, it has not been demonstrated that the products of this gene are actually present in the central nervous system (CNS). In this report, we describe the cellular, spatial, and temporal expression patterns of dsx gene products in the developing and adult CNS by applying RT-PCR and immunohistochemical procedures. dsx gene products were detected in the CNS of 3rd-instar larvae, pupae, and adults. DSX-immunoreactive signals were observed within the brain and in both the thoracic plus abdominal ganglia of the ventral nerve cord. Most, but not all, cells inferred to contain DSX proteins (by the results of genetic controls for antibody specificity) were further determined to be neurons (by coexpression of a protein that marks such CNS cell types). Temporally varying expression of DSX was most prominently observed in the rapidly metamorphosing early and mid-pupal stages, suggesting that this gene contributes to establishment of sexually dimorphic neuronal structures which subserve adult sexual behaviors. Elements of the spatial and temporal patterns of DSX immunoreactivity also imply that sexually dimorphic dsx expression in certain neuronal clusters within the adult CNS could participate in ongoing operations of the mature nervous system with respect to the courtship behaviors that are affected by dsx mutations.

Animals↗

Do obese children become obese adults: childhood predictors of adult disease.

Obesity is a multifactorial disorder influenced by genetic, behavioral, environmental and cultural factors. The prevalence of overweight and obesity in young people is increasing rapidly in both the developed and developing world and are considered today as a global epidemic. Recent studies show that obesity in adult life is heralded at birth and factors such as birth weight, adiposity rebound, socioeconomic status, early maturation and genetic predisposition may have a significant effect on the propensity to develop obesity in adulthood. Avoidance of accelerated weight gain in children should be investigated as a toll of adult obesity prevention.

Adult↗

Genetics of brain function and cognition.

There is overwhelming evidence for the existence of substantial genetic influences on individual differences in general and specific cognitive abilities, especially in adults. The actual localization and identification of genes underlying variation in cognitive abilities and intelligence has only just started, however. Successes are currently limited to neurological mutations with rather severe cognitive effects. The current approaches to trace genes responsible for variation in the normal ranges of cognitive ability consist of large scale linkage and association studies. These are hampered by the usual problems of low statistical power to detect quantitative trait loci (QTLs) of small effect. One strategy to boost the power of genomic searches is to employ endophenotypes of cognition derived from the booming field of cognitive neuroscience. This special issue of Behavior Genetics reports on one of the first genome-wide association studies for general IQ. A second paper summarizes candidate genes for cognition, based on animal studies. A series of papers then introduces two additional levels of analysis in the "black box" between genes and cognitive ability: (1) behavioral measures of information-processing speed (inspection time, reaction time, rapid naming) and working memory capacity (performance on on single or dual tasks of verbal and spatio-visual working memory), and (2) electrophyiosological derived measures of brain function (e.g., event-related potentials). The obvious way to assess the reliability and validity of these endophenotypes and their usefulness in the search for cognitive ability genes is through the examination of their genetic architecture in twin family studies. Papers in this special issue show that much of the association between intelligence and speed-of-information processing/brain function is due to a common gene or set of genes, and thereby demonstrate the usefulness of considering these measures in gene-hunting studies for IQ.

Brain↗

Going to extremes: family structure, children's well-being, and social science.

In this article I argue that public discussions of demographic issues are often conducted in a troubling pattern in which one extreme position is debated in relation to the opposite extreme. This pattern impedes our understanding of social problems and is a poor guide to sound public policies. To illustrate this thesis I use the case of social scientific research examining how children are affected by not living with two biological parents while they are growing up. Over the last decade, I maintain, most of the public, and even many social scientists, have been puzzled and poorly informed by this debate. In particular I consider Judith Wallerstein's clinically based claims of the pervasive, profound harm caused by divorce and, at the other extreme, Judith Rich Harris's reading of behavioral genetics and evolutionary psychology, which leads her to dismiss the direct effects of divorce. Neither extreme gives a clear picture of the consequences of growing up in a single-parent family or a stepfamily.

Child↗

Endotoxin stress responses in chickens from different genetic lines. 1. Sickness, behavioral, and physical responses.

Genetic variation in response to lipopolysaccharide (LPS) challenge was studied in chicken lines divergently selected for high (HGPS) and low (LGPS) group productivity and survivability resulting from cannibalism and flightiness in colony cages and in a Dekalb XL (DXL) commercial line. Six-week-old chicks were randomly assigned to control or experimental groups and were injected intravenously with Escherichia coli LPS (5 mg/kg of BW) or distilled saline (control). Sickness responses were measured at 6, 12, 24, 48, and 72 h following injection (n = 10 at each point in time for each line). Although LPS induced widespread sickness symptoms in all of the treated chicks, the reactions were in a genotypic- and phenotypic-specific manner. Compared with LGPS and DXL chicks, HGPS chicks had acute, transient behavioral and physical changes with less effect on BW gain, organ development, and core temperature, which were in the order HGPS < DXL < LGPS. The effects of heritable factors and LPS challenge on the differential responses among the present lines may reflect each line's unique adaptability to stress and resistance to infection and inflammation. The results suggested that the present chicken lines may provide a valuable animal model for investigating the effects of genetic-environmental interactions on the behavioral and physiological homeostasis in response to stress and disease.

Animals↗

Genetic and environmental influences on MMPI factor scales: joint model fitting to twin and adoption data.

In general, the shared family environment appears to play a negligible role in determining individual differences in personality and interests. Nevertheless, scattered reports of significant shared environmental influence on such variables appear in the literature. Using data from the Texas Adoption Project (TAP), the current study attempted to replicate twin study findings of significant shared environmental variance on four of nine Minnesota Multiphasic Personality Inventory (MMPI) factor scales (Rose, 1988). Conventional behavioral genetic analyses of the adoption data agreed in affirming a significant shared environmental influence on individual differences in Religious Orthodoxy only. Subsequent simultaneous modeling of Rose's twin data and TAP adoption data resulted in three scales (Extraversion, Inadequacy, and Religious Orthodoxy) showing significant shared environmental influence. Again, effects were most substantial for Religious Orthodoxy, where the shared environment accounted for nearly 50% of the variance. It is argued that assortative mating cannot explain this finding.

Adolescent↗

A gerontological cohort study of aged twins: the Osaka University Aged Twin Registry.

We describe subject recruitment and research results from the Osaka University Aged Twin Registry (OUATR). The research focus of OUATR is the genetic and environmental contributions to physical-cognitive-mental aging which we examined in Japanese twins in later adulthood. Within this large-scale registry (12,000 pairs) of oriental twins born between 1900 and 1935, approximately 10% of participants are MZ twins reared apart from early childhood. Two hundred and fifty pairs have had comprehensive medical examinations, including various blood chemical panels, lymphocyte subtests, WAIS (Wechsler Adult Intelligence Scale), and urine analysis. The future foci of this study are primarily on longevity, decline of cognitive functions with aging, bio-physiological functions, lifestyle and behavior genetics, and psycho-spiritual functions.

Activities of Daily Living↗