Systematic mutation analysis of KIAA0767 and KIAA1646 in chromosome 22q-linked periodic catatonia

BACKGROUND: Periodic catatonia is a familial subtype of schizophrenia characterized by hyperkinetic and akinetic episodes, followed by a catatonic residual syndrome. The phenotype has been evaluated in two independent genome-wide linkage scans with evidence for a major locus on chromosome 15q15, and a second independent locus on chromosome 22q(tel). METHODS: In the positional and brain-expressed candidate genes KIAA0767 and KIAA1646, we searched for variants in the complete exons and adjacent splice-junctions as well as in parts of the 5'- and 3'-untranslated regions by means of a systematic mutation screening in individuals from chromosome 22q-linked pedigrees. RESULTS: The mutation scan revealed 24 single nucleotide polymorphisms, among them two rare codon variants (KIAA0767: S159I; KIAA1646: V338G). However, both were neither found segregating with the disease in the respective pedigree nor found at a significant frequency in a case-control association sample. CONCLUSION: Starting from linkage signals at chromosome22q(tel )in periodic catatonia, we screened two positional brain-expressed candidate genes for genetic variation. Our study excludes genetic variations in the coding and putative promoter regions of KIAA0767 and KIAA1646 as causative factors for periodic catatonia

1Identification of genes differentially expressed in the embryonic pig cerebral cortex before and after appearance of gyration

<p>Abstract</p> <p>Background</p> <p>Mammalian evolution is characterized by a progressive expansion of the surface area of the cerebral cortex, an increase that is accompanied by gyration of the cortical surface. The mechanisms controlling this gyration process are not well characterized but mutational analyses indicate that genes involved in neuronal migration play an important function. Due to the lack of gyration of the rodent brain it is important to establish alternative models to examine brain development during the gyration process. The pig brain is gyrated and accordingly is a candidate alternative model.</p> <p>Findings</p> <p>In this study we have identified genes differentially expressed in the pig cerebral cortex before and after appearance of gyration. Pig cortical tissue from two time points in development representing a non-folded, lissencephalic, brain (embryonic day 60) and primary-folded, gyrencephalic, brain (embryonic day 80) were examined by whole genome expression microarray studies. 91 differentially expressed transcripts (fold change >3) were identified. 84 transcripts were annotated and encoding proteins involved in for example neuronal migration, calcium binding, and cytoskeletal structuring. Quantitative real-time PCR was used to confirm the regulation of a subset of the identified genes.</p> <p>Conclusion</p> <p>This study provides identification of genes which are differentially expressed in the pig cerebral cortex before and after appearance of brain gyration. The identified genes include novel candidate genes which could have functional importance for brain development.</p

Diagnosis of inflammatory demyelination in biopsy specimens: a practical approach

Multiple sclerosis is the most frequent demyelinating disease in adults. It is characterized by demyelination, inflammation, gliosis and a variable loss of axons. Clinically and histologically, it shares features with other demyelinating and/or inflammatory CNS diseases. Diagnosis of an inflammatory demyelinating disease can be challenging, especially in small biopsy specimens. Here, we summarize the histological hallmarks and most important neuropathological differential diagnoses of early MS, and provide practical guidelines for the diagnosis of inflammatory demyelinating diseases

Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses

The recent completion of the horse genome and commercial availability of an equine SNP genotyping array has facilitated the mapping of disease genes. We report putative localization of the gene responsible for dwarfism, a trait in Friesian horses that is thought to have a recessive mode of inheritance, to a 2- MB region of chromosome 14 using just 10 affected animals and 10 controls. We successfully genotyped 34 429 SNPs that were tested for association with dwarfism using chi-square tests. The most significant SNP in our study, BIEC2-239376 (P-2df = 4.54 x 10-5, P-rec = 7.74 x 10-6), is located close to a gene implicated in human dwarfism. Fine-mapping and resequencing analyses did not aid in further localization of the causative variant, and replication of our findings in independent sample sets will be necessary to confirm these results