Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility

BACKGROUND: Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. METHODS: The present association study tested whether length variations in the second (more 3') polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO). In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. RESULTS: Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090). Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05). The prevalence of the long CAG repeat (>19 repeats) did not reach statistical significance in migraineurs (P = 0.15), nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively), or between MA vs MO (P = 0.40). CONCLUSION: This association study provides no evidence that length variations of the second polyglutamine array in the N-terminus of the KCNN3 channel exert an effect in the pathogenesis of migraine

Alterações clínicas e laboratoriais anteriores ao desenvolvimento do delirium tremens

Duzentos e trinta pacientes alcoolistas crônicos do sexo masculino internados em hospital psiquiátrico para tratamento do alcoolismo foram examinados clínica e laboratorialmente dentro das primeiras 24 horas da internação. Treze pacientes que desenvolveram delirium tremens (DT) após a internação (grupo I) constituem a casuística deste estudo que visa avaliar a ocorrência de alterações clínicas, hematológicas, bioquímicas hepáticas e eletrolíticas que antecedem ao aparecimento das manifestações do DT. Para análises comparativas foram estudados dois grupos de 26 pacientes cada um, constituídos de pacientes que não entraram em DT na internação atual mas com história pregressa de DT (grupo II) e pacientes aleatoriamente arrolados - amostra aleatória simples obtida empregando tabela de números aleatórios fornecida por computador - que nunca entraram em DT (grupo III). Os pacientes do grupo I apresentavam média de idade significativamente mais baixa e fisicamente encontravam-se em pior estado geral que os do grupo III. As frequências de taxas elevadas de aminotransferases e de hipomagnesemia foram significativamente maiores nos grupos I e II que no grupo III. Os valores plasmáticos médios das aminotransferases, especialmente da aspartato-aminotransferase, estavam significativamente mais elevados nos grupos I e II que no grupo III.Thirteen alcoholic male patients that developed delirium tremens (DT) after admission in a psychiatric hospital for treatment of alcoholism (group I) had their clinical and laboratorial records examined. The laboratory samples were taken during the phase previous at the DT. Data on this group were compared to those of two other groups of alcoholics - 26 patients each - that did not develop DT in the present admission, with (group II) or without (group III) previous history of DT. The patients of group I had significantly lower average age and worse general conditions than the patients of group III. The frequency of elevated aminotransferases and Hypomagnesemia was significantly higher in the group I and II than in the group III. The aminotransferases, especially the aspartate-aminotransferase, were significantly more elevated in the groups I and II

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1,2,3,4,5,6,7,8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located