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DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.

ABSTRACT: Three genes, DYX1C1, DCDC2, and KIAA0319, have been previously associated with dyslexia, neuronal migration, and ciliary function. Three polymorphisms within these genes, rs3743204 (DYX1C1), rs793842 (DCDC2), and rs6935076 (KIAA0319) have also been linked to normal variability of left temporoparietal white matter volume connecting the middle temporal cortex to the angular and supramarginal gyri. Here, we assessed whether these polymorphisms are also related to the cortical thickness of the associated regions during childhood development using a longitudinal dataset of 76 randomly selected children and young adults who were scanned up to three times each, 2 years apart. rs793842 in DCDC2 was significantly associated with the thickness of left angular and supramarginal gyri as well as the left lateral occipital cortex. The cortex was significantly thicker for T-allele carriers, who also had lower white matter volume and lower reading comprehension scores. There was a negative correlation between white matter volume and cortical thickness, but only white matter volume predicted reading comprehension 2 years after scanning. These results show how normal variability in reading comprehension is related to gene, white matter volume, and cortical thickness in the inferior parietal lobe. Possibly, the variability of gray and white matter structures could both be related to the role of DCDC2 in ciliary function, which affects both neuronal migration and axonal outgrowth.

SUBMITTER: Darki F

PROVIDER: S-EPMC6608392 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.

Darki Fahimeh F Peyrard-Janvid Myriam M Matsson Hans H Kere Juha J Klingberg Torkel T

The Journal of neuroscience : the official journal of the Society for Neuroscience 20141001 43

Three genes, DYX1C1, DCDC2, and KIAA0319, have been previously associated with dyslexia, neuronal migration, and ciliary function. Three polymorphisms within these genes, rs3743204 (DYX1C1), rs793842 (DCDC2), and rs6935076 (KIAA0319) have also been linked to normal variability of left temporoparietal white matter volume connecting the middle temporal cortex to the angular and supramarginal gyri. Here, we assessed whether these polymorphisms are also related to the cortical thickness of the assoc ...[more]

PMID: 25339756

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Project description:BackgroundAdolescence is a critical time for brain development. Findings from previous studies have been inconsistent, failing to distinguish the influence of pubertal status and aging on brain maturation. The current study sought to address these inconsistencies, addressing the trajectories of pubertal development and aging by longitudinally tracking structural brain development during adolescence.MethodsTwo cohorts of healthy children were recruited (cohort 1: 9-10 years old; cohort 2: 12-13 years old at baseline). MRI data were acquired for gray matter volume and white matter tract measures. To determine whether age, pubertal status, both or their interaction best modelled longitudinal data, we compared four multi-level linear regression models to the null model (general brain growth indexed by total segmented volume) using Bayesian model selection.ResultsData were collected at baseline (n = 116), 12 months (n = 97) and 24 months (n = 84) after baseline. Findings demonstrated that the development of most regional gray matter volume, and white matter tract measures, were best modelled by age. Interestingly, precentral and paracentral regions of the cortex, as well as the accumbens demonstrated significant preference for the pubertal status model. None of the white matter tract measures were better modelled by pubertal status.LimitationsThe major limitation of this study is the two-cohort recruitment. Although this allowed a faster coverage of the age span, a complete per person trajectory over 6 years of development (9-15 years) could not be investigated.ConclusionsComparing the impact of age and pubertal status on regional gray matter volume and white matter tract measures, we found age to best predict longitudinal changes. Further longitudinal studies investigating the differential influence of puberty status and age on brain development in more diverse samples are needed to replicate the present results and address mechanisms underlying norm-variants in brain development.

Project description:The DCDC2 gene is involved in neuronal migration. Heterotopias have been found within the white matter of DCDC2-knockdown rats. A deletion in DCDC2/intron 2 (DCDC2d), which encompasses a regulatory region named 'regulatory element associated with dyslexia 1' (READ1), increases the risk for dyslexia. We hypothesized that DCDC2d can be associated to alterations of the white matter structure in general and in dyslexic brains.Based on a full-factorial analysis of covariance (ANCOVA) model, we investigated voxel-based diffusion tensor imaging (VB-DTI) data of four groups of subjects: dyslexia with/without DCDC2d, and normal readers with/without DCDC2d. We also tested DCDC2d effects upon correlation patterns between fractional anisotropy (FA) and reading scores.We found that FA was reduced in the left arcuate fasciculus and splenium of the corpus callosum in subjects with versus without DCDC2d, irrespective of dyslexia. Subjects with dyslexia and DCDC2d showed reduced FA, mainly in the left hemisphere and in the corpus callosum; their counterpart without DCDC2d showed similar FA alterations. Noteworthy, a conjunction analysis in impaired readers revealed common regions with lower FA mainly in the left hemisphere. When we compared subjects with dyslexia with versus without DCDC2d, we found lower FA in the inferior longitudinal fasciculus and genu of the corpus callosum, bilaterally. Normal readers with versus without DCDC2d had FA increases and decreases in both the right and left hemisphere.The major contribution of our study was to provide evidence relating genes, brain and behaviour. Overall, our findings support the hypothesis that DCDC2d is associated with altered FA. In normal readers, DCDC2-related anatomical patterns may mark some developmental cognitive vulnerability to learning disabilities. In subjects with dyslexia, DCDC2d accounted for both common - mainly located in the left hemisphere - and unique - a more severe and extended pattern - alterations of white matter fibre tracts.

Project description:BackgroundCholine is an essential nutrient that is pivotal to proper brain development. Research in animal models suggests that perinatal choline deficiency influences neuron development in the hippocampus and cortex, yet these observations require invasive techniques.ObjectiveThis study aimed to characterize the effects of perinatal choline deficiency on gray and white matter development with the use of noninvasive neuroimaging techniques in young pigs.MethodsDuring the last 64 d of the 114-d gestation period Yorkshire sows were provided with a choline-sufficient (CS) or choline-deficient (CD) diet, analyzed to contain 1214 mg or 483 mg total choline/kg diet, respectively. Upon farrowing, pigs (Sus scrofa domesticus) were allowed colostrum consumption for ≤48 h, were further stratified into postnatal treatment groups, and were provided either CS or CD milk replacers, analyzed to contain 1591 or 518 mg total choline/kg diet, respectively, for 28 d. At 30 d of age, pigs were subjected to MRI procedures to assess brain development. Gray and white matter development was assessed through voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) to assess the effects of prenatal and postnatal dietary choline status.ResultsVBM analysis indicated that prenatally CS pigs exhibited increased (P < 0.01) gray matter in the left and right cortex compared with prenatally CD pigs. Analysis of white matter indicated that prenatally CS pigs exhibited increased (P < 0.01) white matter in the internal capsule, putamen-globus pallidus, and right cortex compared with prenatally CD pigs. No postnatal effects (P > 0.05) of choline status were noted for VBM analyses of gray and white matter. TBSS also showed no significant effects (P > 0.05) of prenatal or postnatal choline status for diffusion values along white matter tracts.ConclusionsObservations from this study suggest that prenatal choline deficiency results in altered cortical gray matter and reduced white matter in the internal capsule and putamen of young pigs. With the use of noninvasive neuroimaging techniques, results from our study indicate that prenatal choline deficiency greatly alters gray and white matter development in pigs, thereby providing a translational assessment that may be used in clinical populations.

Dataset Information

DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.

Publications

DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.

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