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Zerdava dogs are considered as one of the many native animal genetic resources of Turkey. However, the genetic characteristics of these dogs and detailed phenotypic studies related to them have not been reported yet. The aim of this study was to determine the morphological and genetic characteristics of Zerdava dogs. Blood samples (n = 100) were collected from Zerdava dogs. The morphological characteristics of these dogs were also taken. The mean live weights of Zerdava dogs were found to be 16.02±0.35 kg. The mean withers height, rump height and body length were measured as 48.20±0.21, 47.08±0.24 and 51.24±0.23 cm, respectively. According to the results of microsatellite markers, the mean FIS (inbreeding coefficient) value was documented as 0.0361±0.0003. Observed (Ho) and expected heterozygosity (He) values were found to be 0.708±0.091 and 0.694±0.077, respectively. In addition, the frequency of A018 (72%) and B001 (16%) haplotypes were high in Zerdava dogs. The mitochondrial DNA sequence results show that the majority of Zerdava dogs originate from two different maternal lines. According to the results, the phenotypic and genotypic variations of Zerdava dogs were low. Therefore, these results may suggest that Zerdava dogs may have been protected by local breeders and can be considered a separate breed. Zerdava köpekleri Türkiye’de birçok yerli hayvan gen kaynaklarından biridir. Ancak, bu köpeklerin genetik ve ayrıntılı fenotipik özellikleri hakkında çalışmaya rastlanılmamaktadır. Bu araştırmanın amacı, Zerdava köpeklerinin morfolojik ve genetik özelliklerini belirlemektir. Zerdava köpeklerinden kan örnekleri (n = 100) alınmıştır. Köpeklere ait morfolojik özellikler de incelenmiştir. Zerdava köpeklerinin ortalama canlı ağırlığı 16.02±0.35 kg olarak bulunmuştur. Ortalama cidago, sağrı yüksekliği ve vücut uzunluğu sırasıyla 48.20±0.21, 47.08±0.24 ve 51.24±0.23 cm’dir. Mikrosatellit işaretleyicilerinin sonuçlarına göre, ortalama FIS (nispi katsayı) değeri 0.0361±0.0003. Gözlenen (Ho) ve beklenen heterozigot (He) değerleri sırasıyla 0.708±0.091 ve 0.694±0.077 olarak tespit edilmiştir. Buna ilave, Zerdava köpeklerinde A018 (%72) ve B001 (%16) haplotiplerinin görülme sıklığı yüksek bulunmuştur. Mitokondriyal DNA sekans sonuçları çoğu Zerdava köpeğinin iki farklı anne soyundan köken aldığını göstermektedir. Mevcut sonuçlara göre, Zerdava köpeklerinin fenotipik ve genotipik varyasyonları düşük olduğu belirlenmiş olup bu köpeklerin yerel yetiştiriciler tarafından korunmuş olabileceği düşünülmektedir.

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Background Associations of Hodgkin's lymphoma with HLA have been reported for many years. In 20-40% of patients with this disorder, Epstein-Barr virus (EBV) is present in the neoplastic cells. Because presentation of EBV antigenic peptides can elicit vigorous immune responses, we investigated associations of the HLA region with EBV-positive and EBV-negative Hodgkin's lymphoma. Methods In a retrospective, population-based study, patients with Hodgkin's lymphoma were reclassified according to the WHO classification, and EBV status was assessed by in-situ hybridisation of EBV-encoded small RNAs. Germline DNA was isolated from 200 patients diagnosed between 1987 and 2000 and from their first-degree relatives. Genotyping was done with 33 microsatellite markers spanning the entire HLA region and two single-nucleotide polymorphisms in the genes for tumour necrosis factor alpha and beta. Classic association analysis and the haplotype sharing statistic were used to compare patients with controls. Findings Classic association analysis (but not the haplotype sharing statistic) showed an association of consecutive markers D6S265 and D6S510 (p=0.0002 and 0.0003), located in the HLA class I region, with EBV-positive lymphomas. The haplotype sharing statistic (but not classic association analysis) showed a significant difference in mean haplotype sharing between patients and controls surrounding marker D6S273 (p=0.00003), located in HLA class III. Interpretation Areas within the HLA class I and class III regions are associated with susceptibility to Hodgkin's lymphoma, the association with class I being specific for EBV-positive disease. This finding strongly suggests that antigenic presentation of EBV-derived peptides is involved in the pathogenesis of EBV-involved Hodgkin's lymphoma. Relevance to practice Polymorphisms in the HLA region could explain ethnic variation in the incidence of Hodgkin's lymphoma. The association of EBV-positive Hodgkin's lymphoma with HLA class I suggests that this polymorphism might affect the proper presentation of EBV antigens to cytotoxic T lymphocytes.

Background Associations of Hodgkin's lymphoma with HLA have been reported for many years. In 20-40% of patients with this disorder, Epstein-Barr virus (EBV) is present in the neoplastic cells. Because presentation of EBV antigenic peptides can elicit vigorous immune responses, we investigated associations of the HLA region with EBV-positive and EBV-negative Hodgkin's lymphoma.Methods In a retrospective, population-based study, patients with Hodgkin's lymphoma were reclassified according to the WHO classification, and EBV status was assessed by in-situ hybridisation of EBV-encoded small RNAs. Germline DNA was isolated from 200 patients diagnosed between 1987 and 2000 and from their first-degree relatives. Genotyping was done with 33 microsatellite markers spanning the entire HLA region and two single-nucleotide polymorphisms in the genes for tumour necrosis factor alpha and beta. Classic association analysis and the haplotype sharing statistic were used to compare patients with controls.Findings Classic association analysis (but not the haplotype sharing statistic) showed an association of consecutive markers D6S265 and D6S510 (p=0.0002 and 0.0003), located in the HLA class I region, with EBV-positive lymphomas. The haplotype sharing statistic (but not classic association analysis) showed a significant difference in mean haplotype sharing between patients and controls surrounding marker D6S273 (p=0.00003), located in HLA class III.Interpretation Areas within the HLA class I and class III regions are associated with susceptibility to Hodgkin's lymphoma, the association with class I being specific for EBV-positive disease. This finding strongly suggests that antigenic presentation of EBV-derived peptides is involved in the pathogenesis of EBV-involved Hodgkin's lymphoma.Relevance to practice Polymorphisms in the HLA region could explain ethnic variation in the incidence of Hodgkin's lymphoma. The association of EBV-positive Hodgkin's lymphoma with HLA class I suggests that this polymorphism might affect the proper presentation of EBV antigens to cytotoxic T lymphocytes.

Background Common single-nucleotide polymorphisms (SNPs) in ten chromosomal loci have been shown to predispose to colorectal cancer (CRC) in genome-wide association studies. A plausible biological mechanism of CRC susceptibility associated with genetic variation has so far only been proposed for three loci, each pointing to variants that affect gene expression through distant regulatory elements. In this study, we aimed to gain insight into the molecular basis of seven low-penetrance CRC loci tagged by rs4779584 at 15q13, rs10795668 at 10p14, rs3802842 at 11q23, rs4444235 at 14q22, rs9929218 at 16q22, rs10411210 at 19q13, and rs961253 at 20p12. Methods Possible somatic gain of the risk allele or loss of the protective allele was studied by analyzing allelic imbalance in tumour and corresponding normal tissue samples of heterozygous patients. Functional variants were searched from in silico predicted enhancer elements locating inside the CRC-associating linkage-disequilibrium regions. Results No allelic imbalance targeting the SNPs was observed at any of the seven loci. Altogether, 12 SNPs that were predicted to disrupt potential transcription factor binding sequences were genotyped in the same population-based case-control series as the seven tagging SNPs originally. None showed association with CRC. Conclusions The results of the allelic imbalance analysis suggest that the seven CRC risk variants are not somatically selected for in the neoplastic progression. The bioinformatic approach was unable to pinpoint cancer-causing variants at any of the seven loci. While it is possible that many of the predisposition loci for CRC are involved in control of gene expression by targeting transcription factor binding sites, also other possibilities, such as regulatory RNAs, should be considered.