Complex aetiology of an apparently Mendelian form of Mental Retardation

<p>Abstract</p> <p>Background</p> <p>Mental Retardation is a common heterogeneous neurodevelopment condition, which causes are still largely elusive. It has been suggested that half of the phenotypic variation of intelligence is explained by genetic variation. And genetic or inherited factors indeed account for most of the cases of mental retardation with an identifiable cause. However, only a few autosomal genes have been mapped and identified to date. In this report, the genetic causes for an apparently recessive form of mental retardation, in a large nordern swedish pedigree, are investigated.</p> <p>Methods</p> <p>After extensive evaluation of the patients, which ruled out recognizable patterns of malformation and excluded known causes of MR, a comprehensive genome-wide linkage analysis, with 500 microsatellite markers, was performed in 24 members of this family. Additionally, a genome-wide copy number analysis, using an affimetrix 250 K SNP chip, was performed in this pedigree.</p> <p>Results</p> <p>No significant LOD score was found with either parametric and non-parametric linkage analysis. The highest scores are located at chromosomes 13, 15 and 17. Genome-wide copy number analysis identified no clear cause for the disorder; but rather, several variants were present in the family members, irrespective of their affected status.</p> <p>Conclusion</p> <p>These results suggest that mental retardation in this family, unlikely what was expected, has a heterogeneous aetiology; and that several lower effect genes variants might be involved. To demonstrate such effects, our family may be too small. This study also indicates that the ascertainment of the cause of MR may be challenging, and that a complex aetiology may be present even within a pedigree, constituting an additional obstacle for genetic counselling. Variants in genes involved in molecular mechanisms of cellular plasticity, in genes involved in the development of underlying neural architectures, and in genes involved in neurodevelopment and in the ongoing function of terminally differentiated neurons may underlie the phenotypic variation of intelligence and explain instances of intellectual impairment.</p

Approach to epigenetic analysis in language disorders

Language and learning disorders such as reading disability and language impairment are recognized to be subject to substantial genetic influences, but few causal mutations have been identified in the coding regions of candidate genes. Association analyses of single nucleotide polymorphisms have suggested the involvement of regulatory regions of these genes, and a few mutations affecting gene expression levels have been identified, indicating that the quantity rather than the quality of the gene product may be most relevant for these disorders. In addition, several of the candidate genes appear to be involved in neuronal migration, confirming the importance of early developmental processes. Accordingly, alterations in epigenetic processes such as DNA methylation and histone modification are likely to be important in the causes of language and learning disorders based on their functions in gene regulation. Epigenetic processes direct the differentiation of cells in early development when neurological pathways are set down, and mutations in genes involved in epigenetic regulation are known to cause cognitive disorders in humans. Epigenetic processes also regulate the changes in gene expression in response to learning, and alterations in histone modification are associated with learning and memory deficits in animals. Genetic defects in histone modification have been reversed in animals through therapeutic interventions resulting in rescue of these deficits, making it particularly important to investigate their potential contribution to learning disorders in humans

Physical Attractiveness, Altruism and Cooperation in an Ultimatum Game

Explaining cooperative tendencies through an evolutionary lens has been problematic for theorists. Traditional explanations derive from theories of reciprocity, biological markets, and more recently via partner choice and sexual selection. The sexual selection hypothesis has been tested within game-theoretic frameworks gaining empirical sup- port in explaining the evolution of altruism. Males have been found to be more altruistic towards attractive females. However, previous research has predominantly adopted a design where participants are not engaging with ‘real people’. Instead, participants make decisions when viewing images or hypothetical scenarios without visual cues. The present study aimed to investigate the sexual selection hypothesis using a face-to-face game theoretic framework. One hundred and thirty-eight participants played a 2-round ultimatum game with chocolate coins as the monetary incentive. We find, that physical attractiveness had no influence on generosity and cooperation when participants play a face-to-face ultimatum game. Instead, proposers were fair when allocating stakes, offering an average of half the endowment to responders. This study refutes the link between the sexual selection hypothesis and generosity when playing economic games with real people. Fairness appeared to drive generosity and cooperation

Implicit theories about personality and intelligence and their relationship to actual personality and intelligence

Spinath B, Spinath FM, Riemann R, Angleitner A. Implicit theories about personality and intelligence and their relationship to actual personality and intelligence. PERSONALITY AND INDIVIDUAL DIFFERENCES. 2003;35(4):939-951.Implicit theories about the malleability of human attributes have proven to be valuable predictors of cognitions, affects, and behavior in the field of achievement motivation and social judgments (see Dweck, 1999). Implicit theories in the sense used by Dweck distinguish between the belief that human attributes are fixed (entity theory) or malleable (incremental theory). The present study examined to what extent implicit theories are related to personality and intelligence. A sample of 592 adults completed self-report measures of implicit theories and the Big Five factors of personality as well as two short forms of intelligence tests. The results support the notion that implicit theories about the malleability of personality and intelligence are largely unrelated to actual personality and intelligence. Thus, the results represent further evidence for the high discriminant validity of the implicit theories construct. (C) 2003 Elsevier Ltd. All rights reserved

Genetic and environmental influences on observed personality: Evidence from the German observational study of adult twins

Borkenau P, Riemann R, Angleitner A, Spinath FM. Genetic and environmental influences on observed personality: Evidence from the German observational study of adult twins. JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY. 2001;80(4):655-668.Previous behavior-genetic research on adult personality relied primarily on self-reports or peer reports that may be subject to contrast effects, resulting in biased estimates of genetic and environmental influences. In the German Observational Study of Adult Twins (GOSAT), personality traits of 168 monozygotic (MZ) and 132 dizygotic (DZ) twin pairs were rated on 35 adjective scales, largely markers of the Big 5. The ratings were provided by 120 judges who never met the toxins but observed videotaped behaviors of 1 twin of each pair in 1 of 15 different settings. The aggregated video-based trait ratings were highly reliable, and substantial correlations were obtained between MZ as well as DZ twin,, Model-fit analyses suggested about 40% genetic, 25% shared environmental, and 35% nonshared environmental influence. Extraversion was the only trait that seemed not to be influenced by shared environment

Similarity of childhood experiences and personality resemblance in monozygotic and dizygotic twins: a test of the equal environments assumption

Borkenau P, Riemann R, Angleitner A, Spinath FM. Similarity of childhood experiences and personality resemblance in monozygotic and dizygotic twins: a test of the equal environments assumption. PERSONALITY AND INDIVIDUAL DIFFERENCES. 2002;33(2):261-269.The equal environments assumption suggests that the environment does not contribute more strongly to the similarity of monozygotic (MZ) compared to dizygotic (DZ) twins. It was tested in 525 MZ, 200 same-sex DZ, and 68 opposite-sex DZ twin pairs. Almost 80% of the twins were female, and their age varied widely around a mean of 32 years. Similarity of twin environments was assessed by a self-report questionnaire on childhood experiences, and personality resemblance was measured using the self-report and peer-report versions of the NEO-Five-Factor Inventory. MZ twins reported more similar experiences than DZ twins and were also more alike in personality. Across twin pairs, however, treatment similarity was unrelated to personality resemblance, except in the combined group of MZ and DZ twins. These results are consistent with the equal-environments assumption. (C) 2002 Elsevier Science Ltd. All rights reserved

German Observational Study of Adult Twins (GOSAT): A multimodal investigation of personality, temperament and cognitive ability

Spinath FM, Angleitner A, Borkenau P, Riemann R, Wolf H. German Observational Study of Adult Twins (GOSAT): A multimodal investigation of personality, temperament and cognitive ability. Twin Research. 2002;5(5):372-375.T he German Observational Study of Adult Twins (GOSAT) is the largest population-based observational twin study in Germany to date. Embedded in the Bielefeld Longitudinal Study of Adult Twins (BiLSAT), it addresses the etiology of personality, temperament and cognitive ability in a sample of 300 monozygotic (MZ) and dizygotic (DZ) adult twin pairs between 18 and 70 years of age. A major aim of the GOSAT lies in the utilization of different modes of measurement, (i.e., peer reports and observational data), in addition to self-reports which have been used predominantly in past behavioral genetic research on personality and temperament in adults. Participants completed a full day assessment at the University of Bielefeld including videotaped social interactions and presentations, psychometric intelligence tests and computerized elementary cognitive tasks as well as objective measures and unobtrusive behavior counts. The research design of the GOSAT was devised to reduce the potential impact of systematic rater bias on estimates of genetic and environmental influences to a minimum. In combination with extensive self and peer report data on key personality and personality related dimensions available from the BiLSAT, the GOSAT provides a rich dataset, which currently includes DNA samples from 80% of its participants

Multimodal investigation of personality and cognitive ability. Results from two German twin studies BiLSAT and GOSAT

Spinath FM, Wolf H, Angleitner A, Borkenau P, Riemann R. Multimodal investigation of personality and cognitive ability. Results from two German twin studies BiLSAT and GOSAT. ZEITSCHRIFT FUR SOZIOLOGIE DER ERZIEHUNG UND SOZIALISATION. 2005;25(2):146-161.The German Observational Study of Adult Twins (GOSAT) is the largest population-based observational twin study in Germany to date. Embedded in the Bielefeld Longitudinal Study of Adult Twins (BiLSAT), it addresses the etiology of personality and cognitive ability in a sample of 300 monozygotic (MZ) and dizygotic (DZ) adult twin pairs between 18 and 70 years of age. A major aim of the GOSAT lies in the utilization of different modes of measurement, i.e. peer reports and observational data in addition to self-reports, which have been used predominantly in past behavioral genetic research on personality in adults. Participants completed a full day assessment at the University of Bielefeld, including videotaped social interactions and presentations, psychometric intelligence tests, and computerized elementary cognitive tasks, as well as objective measures and unobtrusive behavior counts. The research design of the GOSAT was devised to reduce the potential impact of systematic rater bias on estimates of genetic and environmental influences to a minimum. Together with extensive self- and peer report data on personality dimensions available from the BiLSAT, the GOSAT provides a unique multimodal dataset to address the etiology of personality and intelligence. The paper provides an overview of results from GOSAT and BiLSAT to the present day

Lack of association between polymorphisms of the dopamine D-4 receptor gene and personality

Strobel A, Spinath FM, Angleitner A, Riemann R, Lesch KP. Lack of association between polymorphisms of the dopamine D-4 receptor gene and personality. NEUROPSYCHOBIOLOGY. 2003;47(1):52-56.Recent studies have suggested a role of two polymorphisms of the dopamine D-4 receptor gene (DRD4 exon III and -521C/T) in the modulation of personality traits such as 'novelty seeking' or 'extraversion', which are supposed to be modulated by individual differences in dopaminergic function. However, several replication studies have not provided positive findings. The present study was performed to further investigate whether DRD4 exon III and -521C/T are associated with individual differences in personality. One hundred and fifteen healthy German volunteers completed the NEO-Five-Factor Inventory (NEO-FFI) and were genotyped for the two DRD4 polymorphisms. We found no association between DRD4 exon III and -521C/T, respectively, and estimated novelty seeking, NEO-FFI extraversion or other personality factors. Our findings are in line with several earlier studies which have failed to replicate the initial association results. Hence, our data do not provide evidence for a role of DRD4 exon III and the -521C/T polymorphism in the modulation of novelty seeking and extraversion. Copyright (C) 2003 S. Karger AG, Basel