IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

Circular dichroism spectra of N, N-dimethyl-L-amino acids

The circular dichroism spectra in the region 190-300 nm have been measured at pH 1 and pH 13 in aqueous solution for a series of N, N-dimethyl-L-amino acids. A dominant positive Cotton effect is generally observed between 205 and 225 nm as has been found previously for the parent L-amino acids. These results are consistent with the same conformer being dominant for both series of compounds

Circular dichroism spectra of asymmetric unidentate amine complexes of cobalt(III)

The preparations of pentaamminecobalt(III) complexes of a series of asymmetric unidentate amines are reported. The circular dichroism spectra for the (S)-amines show negative Cotton effects under the A → T absorption band, which are somewhat solvent dependent but independent of temperature down to -190°C. The vicinal effect from 1-cyclohexylethylamine was comparable to that from analogous aromatic compounds, but the simpler alkyl derivatives were found to impose smaller rotational strengths on the d-d transitions. The lack of measurable c.d. in the visible region for tetraammine((S)-butane-1, 3-diamine)cobalt(III) is reported and discussed in the light of the other studies

Circular Dichroism Spectra of Tetraamminecobalt(III) Complexes of Amino Alcohols

The circular dichroism spectra are reported for tetraamminecobalt(III) complexes with the chiral amino alcohols 2-aminopropan-1-ol, 2-aminobutan-1-ol, l-aminopropan-2-ol, 2-amino-1-phenyl- ethanol, ψ-ephedrine and ephedrine with the alcohol groups protonated (OH) and deprotonated (O-). The solvent dependence of the chemical shifts of the NH protons was investigated to determine the effects of stereoselective solvation on the circular dichroism, but, in contrast to some other related systems, the chemical shift difference between the two NH2protons was relatively insensitive to solvent. Consistent with this, the circular dichroism spectra of the tetraphenylborate salts of the deprotonated complexes were found not to be markedly dependent on solvent. Tetraammine- ((-)-ψ-ephedrine)cobalt(III) and tetraammine((-)-ephedrine)cobalt(iii) were found to have the same signs of Cotton effects for the various d-d transitions, whereas bis((-)-ψ-ephedrine)copper(ii) and bis((-)-ephedrine)copper(ii) had opposite signs. This has been explained in terms of different conformer populations in the cobalt(iii) and copper(ii) systems

Solvent-dependent circular dichroism of trans-disubstituted Bis(R-propane-1,2-diamine)cobalt(III) complexes

The circular dichroism spectra of trans-disubstituted bis(R-propane-1,2-diamine)cobalt(III) complexes are reported for an extended series of solvents. The observed variations in the spectra of the dichloro and dibromo complexes are analysed in terms of stereoselective solvation at the diamine N-H protons, and also the ion association between the complexes and their counter-ions. The solvation of these dihalo complexes, which was studied by p.m.r., showed a preference for hydrogen-bond formation with the equatorial N-H protons, rendering the donor nitrogens asymmetric and thus introducing a new source of dissymmetry close to the metal ion chromophore. This affected a decrease in the positive rotational strength of the 1A1g {equivalent to} 1Eg (D4h) transition, and a positive contribution to the rotational strength of the 1A1g {equivalent to} 1A2g (D4h) component. Ion association of the dihalo complexes was evaluated by a comparison of the circular dichroism of the tetraphenylborate and halide salts. The tendency for ion association was much greater for the tripositive diammine complex. However, stereospecific solvation was of little importance and the circular dichroism spectra did not show any marked solvent dependence for the tetraphenylborate salt