Human ROBO1 regulates white matter structure in corpus callosum

The axon guidance receptor, Robo1, controls the pathfinding of callosal axons in mice. To determine whether the orthologous ROBO1 gene is involved in callosal development also in humans, we studied polymorphisms in the ROBO1 gene and variation in the white matter structure in the corpus callosum using both structural magnetic resonance imaging and diffusion tensor magnetic resonance imaging. We found that five polymorphisms in the regulatory region of ROBO1 were associated with white matter density in the posterior part of the corpus callosum pathways. One of the polymorphisms, rs7631357, was also significantly associated with the probability of connections to the parietal cortical regions. Our results demonstrate that human ROBO1 may be involved in the regulation of the structure and connectivity of posterior part of corpus callosum.Peer reviewe

Genomic sequencing of a dyslexia susceptibility haplotype encompassing ROBO1

Background: The DYX5 locus for developmental dyslexia was mapped to chromosome 3 by linkage study of a large Finnish family, and later, roundabout guidance receptor 1 (ROBO1) was implicated as a candidate gene at DYX5 with suppressed expression from the segregating rare haplotype. A functional magnetoencephalographic study of several family members revealed abnormal auditory processing of interaural interaction, supporting a defect in midline crossing of auditory pathways. In the current study, we have characterized genetic variation in the broad ROBO1 gene region in the DYX5-linked family, aiming to identify variants that would increase our understanding of the altered expression of ROBO1. Methods: We have used a whole genome sequencing strategy on a pooled sample of 19 individuals in combination with two individually sequenced genomes. The discovered genetic variants were annotated and filtered. Subsequently, the most interesting variants were functionally tested using relevant methods, including electrophoretic mobility shift assay (EMSA), luciferase assay, and gene knockdown by lentiviral small hairpin RNA (shRNA) in lymphoblasts. Results: We found one novel intronic single nucleotide variant (SNV) and three novel intergenic SNVs in the broad region of ROBO1 that were specific to the dyslexia susceptibility haplotype. Functional testing by EMSA did not support the binding of transcription factors to three of the SNVs, but one of the SNVs was bound by the LIM homeobox 2 (LHX2) protein, with increased binding affinity for the non-reference allele. Knockdown of LHX2 in lymphoblast cell lines extracted from subjects from the DYX5-linked family showed decreasing expression of ROBO1, supporting the idea that LHX2 regulates ROBO1 also in human. Conclusions: The discovered variants may explain the segregation of dyslexia in this family, but the effect appears subtle in the experimental settings. Their impact on the developing human brain remains suggestive based on the association and subtle experimental support.Peer reviewe

Genetic Susceptibility to Non-Necrotizing Erysipelas/Cellulitis

Peer reviewe

Increased Expression of the Dyslexia Candidate Gene DCDC2 Affects Length and Signaling of Primary Cilia in Neurons

Peer reviewe

Taxation of corporates in the Czech Republic and Austria

This bachelor thesis aims to determine and compare the tax burden of corporates in terms of tax on corporate profits in the Czech Republic and Austria. It consists of two parts. The first one is focused on introduction of the corporate tax structure in both countries. The second part compares the tax burden using real and fictitious indicators. The analysis of all obtained values shows that Austria is subject of higher corporate tax burden. Despite that, for some companies, other aspects, such as the possibility of group taxation in Austria, may be relevant

Affymetrix HMA250K results for 3q22.

<p>The haplotype that was significantly associated to erysipelas in Haploview is marked with bold letters in the “Associated allele” column. Significant p-values in Haploview or Haplotype pattern mining (HPM) for individual SNPs are also highlighted in bold. SNPs belonging to the associated haplotype and a significant p-value in Haploview, and with a significant p-value in HPM, and that showed shared heterozygosity among cases are marked with an asterisk.</p

The NPL_all scores from initial non-parametric linkage analysis for the chromosomes showing suggestive linkage.

<p>Allele frequencies for the Affymetrix HMA10K Array were estimated using 20 affected individuals from six families and MERLIN was used for multipoint NPL analysis.</p