GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function : a report from the COGENT consortium

CORRIGENDUM Molecular Psychiatry (2017) 22, 1651–1652 http://www.nature.com/articles/mp2017197.pdfThe complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (PPeer reviewe

MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/ aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs

Histology of the Pharyngeal Constrictor Muscle in 22q11.2 Deletion Syndrome and Non-Syndromic Children with Velopharyngeal Insufficiency

Plastic surgeons aim to correct velopharyngeal insufficiency manifest by hypernasal speech with a velopharyngoplasty. The functional outcome has been reported to be worse in patients with 22q11.2 deletion syndrome than in patients without the syndrome. A possible explanation is the hypotonia that is often present as part of the syndrome. To confirm a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome, specimens of the pharyngeal constrictor muscle were taken from children with and without the syndrome. Histologic properties were compared between the groups. Specimens from the two groups did not differ regarding the presence of increased perimysial or endomysial space, fiber grouping by size or type, internalized nuclei, the percentage type I fibers, or the diameters of type I and type II fibers. In conclusion, a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome could not be confirmed

Quadruple chemical bonding in the diatomic anions TcN−, RuC−, RhB−, and PdBe−

Quadruple bonding is uncommon for main group elements and the identification of species forming such bonds is remarkably interesting particularly in diatomic anions for which there is a lack of information. Here, it is found that the MX− anions, TcN−, RuC−, RhB−, and PdBe−, present quadruple bonding, as do the corresponding MX neutrals, even though a different type of σ2 bond is involved in ∑+ states of neutral and anions. Specifically, the ground states (X2Δ or X2∑+) of the four anions and their first excited states (A2∑+ or A2Δ) of TcN−, RuC−, and RhB− present quadruple bonds consisting of two σ and two π bonds: (4dz2 − 2pz)2, 5pz0 ← 2s2, (4dxz − 2px)2, and (4dyz − 2py)2. Bond lengths, dissociation energies, spectroscopic data and electron affinities were calculated via high-level multireference and coupled-cluster methodology using the aug–cc–pV5ZX(-PP)M basis set. Strong bonding results in short bond lengths ranging from 1.602 (TcN−) to 1.944 (PdBe−) Å. Adiabatic (diabatic) binding energies reach up to 139 (184) kcal/mol. Electron affinities (EA) were calculated at 1.368 (TcN), 1.242 (RuC), 0.873 (RhB), 0.743 (PdBe) eV. Only for RhB has EA been measured experimentally at 0.961 eV, in good agreement with the value reported here. © 2021 Wiley Periodicals LLC

CH(X2Π, a4Σ-) ⋯ OH 2 and CH2(X̃3B1, ãA 1) ⋯ OH2 interactions. A first principles investigation

We have investigated the interaction of the methylidene, CH(X 2Π, a4Σ-) and methylene, CH 2(X̃3B1, ã1A1) with H2O, employing the (P)MPn (n = 2, 4) techniques in conjunction with the sequence of correlation consistent basis sets aug-cc-pVxZ, x = 2, 3, and 4. For the CH⋯OH2 system, we have located four minima (m) and three transition states (ts) and for the CH2⋯OH 2, five minima and four transition states. All our results have been corrected for zero-point energy (ZPE) and basis set superposition errors (BSSE), while for the most important m_ structures, we report complete basis set (CBS) interaction limits. We also report fully optimized geometries, harmonic frequencies, dipole moments, Mulliken charges, and potential energy curves. The highest CH(X2Π)⋯OH2 (ml_2Π) and CH2(ã1A 1)⋯OH2 (m1_1A1) interactions are the result of electron transfer from the oxygen atom to the empty p π orbitals of CH(X2Π) and CH2(ã 1A1), respectively (ylide-like structures). At the (P)MP4/AQZ//MP2/ATZ level, including ZPE, BSSE, and CBS extrapolation, we obtain ΔE0(BSSE)+CBS = -9.36 kcal/mol at rC⋯O = 1.752 Å, and -9.73 kcal/mol at rC⋯O = 1.741 Å for the m1_2Π and m1_1A1, respectively. © 2005 Wiley Periodicals, Inc

The dipole moments of the excited states of FeC

With the purpose of comparing expectation dipole moment values 〈μ〉 with finite-field obtained dipole moments μ FF, we recalculated by the finite-field method previously reported 〈μ〉 values of 38 excited states of FeC. In most of the cases μ FF is significantly larger than 〈μ〉.© 2005 American Institute of Physics