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The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses.

ABSTRACT: Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with handedness and language lateralization. Significant gene ontology sets for handedness were anatomical structure development, pattern specification (especially asymmetry formation) and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that handedness and language lateralization are ontogenetically independent, complex phenotypes.

SUBMITTER: Schmitz J

PROVIDER: S-EPMC5498560 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses.

Schmitz Judith J Lor Stephanie S Klose Rena R Güntürkün Onur O Ocklenburg Sebastian S

Frontiers in psychology 20170706

Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performe ...[more]

PMID: 28729848

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Project description:Lateralization, or asymmetry in form and/or function, is found in many animal species. Brain lateralization is considered adaptive for an individual, and often results in "handedness," "footedness," or a side preference, manifest in behavior and morphology. We tested for lateralization in several behaviors in a wild population of Magellanic penguins Spheniscus magellanicus breeding at Punta Tombo, Argentina. We found no preferred foot in the population (each penguin observed once) in stepping up onto an obstacle: 53% stepped up with the right foot, 47% with the left foot (n = 300, binomial test p = 0.27). We found mixed evidence for a dominant foot when a penguin extended a foot for thermoregulation, possibly depending on the ambient temperature (each penguin observed once). Penguins extended the right foot twice as often as the left foot (n = 121, p < 0.0005) in 2 years when we concentrated our effort during the heat of the day. In a third year when we observed penguins early and late in the day, there was no preference (n = 232, p = 0.59). Penguins use their flippers for swimming, including searching for and chasing prey. We found morphological evidence of a dominant flipper in individual adults: 60.5% of sternum keels curved one direction or the other (n = 76 sterna from carcasses), and 11% of penguins had more feather wear on one flipper than the other (n = 1217). Right-flippered and left-flippered penguins were equally likely in both samples (keels: p = 0.88, feather wear: p = 0.26), indicating individual but not population lateralization. In fights, aggressive penguins used their left eyes preferentially, consistent with the right side of the brain controlling aggression. Penguins that recently fought (each penguin observed once) were twice as likely to have blood only on the right side of the face (69%) as only on the left side (31%, n = 175, p < 0.001). The proportion of penguins with blood only on the right side increased with the amount of blood. In most fights, the more aggressive penguin used its left eye and attacked the other penguin's right side. Lateralization depended on the behavior tested and, in thermoregulation, likely on the temperature. We found no lateralization or mixed results in the population of Magellanic penguins in three individual behaviors, stepping up, swimming, and thermoregulation. We found lateralization in the population in the social behavior fighting.

Project description:Introduction: Lateralization in brain function has been associated with age and sex in previous work; however, there has been less focus on lateralization of functional networks during development. Aim: We aim to examine laterality in typical development; a clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. Material and Methods: In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6-10 years. This is an extension of our previous work on normal aging in adults, where we now assess whether there are similar patterns in children. Results: Unlike the results from our study of healthy aging in adults, which showed a decrease in laterality with increasing age, in this study we found both decreases and increases in lateralization in multiple networks with development. For example, auditory and sensorimotor regions had greater bilateral connectivity with development, whereas regions including the dorsolateral frontal cortex (Brodmann area left 9 and left 46) showed an increase in left lateralization with development. Conclusion: Our findings support a complex, nonlinear association between laterality and age in school-age children, a time when brain function and structure are developing rapidly. We also found brain networks in which laterality was significantly associated with sex, handedness, and intelligence quotient, but we did not find any significant association with behavioral scores. Impact statement Lateralization in brain function has been associated with age and sex in several previous studies; however, there has been less focus on lateralization of functional networks during development. A clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6-10 years.

Dataset Information

The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses.

Publications

The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses.

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