Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, Pmeta = 2.5 × 10−9, OR[T] = 0.81) and 17q21.32 (rs72823592, Pmeta = 9.3 × 10−9, OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, Pmeta = 9.1 × 10−9, OR[T] = 0.68) and at 1q43 for JME (rs12059546, Pmeta = 4.1 × 10−8, OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, Pmeta = 4.0 × 10−6) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndrome

Genome-Wide Copy Number Variation in Epilepsy: Novel Susceptibility Loci in Idiopathic Generalized and Focal Epilepsies

Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or schizophrenia. In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism, schizophrenia, and epilepsy

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

Cajus Suetonius Tranquillus

CAJUS SUETONIUS TRANQUILLUS Cajus Suetonius Tranquillus Cajus Suetonius Tranquillus (Erster Band) Cajus Suetonius Tranquillus (Zweiter Band

Cajus Suetonius Tranquillus

CAJUS SUETONIUS TRANQUILLUS Cajus Suetonius Tranquillus (-) Cajus Suetonius Tranquillus (Zweiter Band) ([1]) Titelseite ([1]) Cajus Cäsar Caligula. (1) Tiberius Claudius Drusus Cäsar. (96) Nero Claudius Cäsar. (169) Sergius Sulpicius Galba. (257) Marcus Salvius Otho. (288) Aulus Vitellius. (308) Titus Flavius Vespasianus. (335) Titus Flavius Vespasianus Augustus. (372) Titus Flavius Domitianus. (387) Literarische Notiz vom Cajus Suetonius Tranquillus aus Joh. Albert Fabricius lateinischen von Joh. August Ernesti vermehrten Bibliothek. (427

Cajus Suetonius Tranquillus

CAJUS SUETONIUS TRANQUILLUS Cajus Suetonius Tranquillus (-) Cajus Suetonius Tranquillus (Erster Band) ( - ) Cover ( - ) Titelseite ([1]) Widmung ([2]) Wolgebohrner Herr, Hochzuverehrender Herr Consulent! ([1]) Vorrede. ([5]) Julius Cäsar. (1) Cäsar Octavianus Augustus. (103) Tiberius. (271) Auszug des neuen Avertissements von den Uebersetzungen der Griechen und Lateiner. ([1]

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Абитуриентов ждет факультет автоматики и электромеханики - составная часть УНПК "Электромеханик" / А. В. ЛоосБольшие возможности / А. ЯковлевОни учат студентов / И. В. СлащевНаука о контактах. Электрические аппараты / Д. СанниковОт электробритвы до космического корабля. Электрические машины / М. СанниковаЧтобы работали роботы. Электропривод и автоматизация промышленных установок / А. АлехинСистемы ориентации летательных аппаратов. Гироскопические приборы и устройства / В. И. КопытовБыстродействие и точность. Электрооборудование / А. В. ЛоосНадёжность, безопасность. Электроизоляционная и кабельная техника / Ю. П. ПохолковТретий трудовой / Г. МихайловЭта разнообразная студенческая жизнь / М. ГанжелюкУсловия прием