Browsing by Subject "Brain function"
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Item Open Access Demographically-based evaluation of genomic regions under selection in domestic dogs(Public Library of Science, 2016) Freedman, A. H.; Schweizer, R. M.; Vecchyo, D. Ortega-Del; Han, E.; Davis, B. W.; Gronau, I.; Silva, P. M.; Galaverni, M.; Fan, Z.; Marx, P.; Lorente-Galdos, B.; Ramirez, O.; Hormozdiari, F.; Alkan C.; Vilà, C.; Squire K.; Geffen, E.; Kusak, J.; Boyko, A. R.; Parker, H. G.; Lee C.; Tadigotla, V.; Siepel, A.; Bustamante, C. D.; Harkins, T. T.; Nelson, S. F.; Marques Bonet, T.; Ostrander, E. A.; Wayne, R. K.; Novembre, J.Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rdtop hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. © 2016, Public Library of Science. All Rights Reserved.Item Open Access Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses(Springer Verlag, 2017) Gunbey, H. P.; Bilgici, M. C.; Aslan, K.; Has, A. C.; Ogur, M. G.; Alhan, A.; Incesu, L.Objectives: To provide an initial assessment of white matter (WM) integrity with diffusion tensor imaging (DTI) and the accompanying volumetric changes in WM and grey matter (GM) through volumetric analyses of young children with Down’s syndrome (DS). Methods: Ten children with DS and eight healthy control subjects were included in the study. Tract-based spatial statistics (TBSS) were used in the DTI study for whole-brain voxelwise analysis of fractional anisotropy (FA) and mean diffusivity (MD) of WM. Volumetric analyses were performed with an automated segmentation method to obtain regional measurements of cortical volumes. Results: Children with DS showed significantly reduced FA in association tracts of the fronto-temporo-occipital regions as well as the corpus callosum (CC) and anterior limb of the internal capsule (p < 0.05). Volumetric reductions included total cortical GM, cerebellar GM and WM volume, basal ganglia, thalamus, brainstem and CC in DS compared with controls (p < 0.05). Conclusion: These preliminary results suggest that DTI and volumetric analyses may reflect the earliest complementary changes of the neurodevelopmental delay in children with DS and can serve as surrogate biomarkers of the specific elements of WM and GM integrity for cognitive development. Key Points: • DS is the most common genetic cause of intellectual disability. • WM and GM structural alterations represent the neurological features of DS. • DTI may identify the earliest aging process changes. • DTI-volumetric analyses can serve as surrogate biomarkers of neurodevelopment in DS. © 2016, European Society of Radiology.