Gene Discovery and Data Sharing in Genome Wide Association Analyses: Lessons Form AIDS Genetic Restriction Genes

As genome wide association studies plus whole genome sequence analyses for complex human disease determinants are expanding, it seems useful to develop strategies to facilitate large data sharing, rapid replication and validation of provocative statistical associations that straddle the threshold for genome wide significance. At this conference, we shall announce GWATCH, (Genome Wide Association Tracks Chromosome Highway) a web based data release platform that can freely display and inspect unabridged genome tracked association data without compromising privacy or Informed Consent constrictions, allowing for rapid discovery and replication opportunities. We illustrate the utility with HIV-AIDS resistance genes screened in combined large multicenter cohort studies GWAS (MACS, HGDS, MHGS, ALLIVE, LSOCA HOMER) developed and studied over the last decades

Steric control in the metal-ligand electron transfer of iminopyridine-ytterbocene complexes

International audienceA systematic study of reactions between Cp*Yb-2(THF) (Cp* = eta(5)-C5Me5, 1) and iminopyridine ligands (IPy = 2,6-(Pr2C6H3N)-Pr-i=CH(C5H3N-R), R = H (2a), 6-C4H3O (2b), 6-C4H3S (2c), 6-C6H5 (2d)) featuring similar electron accepting properties but variable denticity and steric demand, has provided a new example of steric control on the redox chemistry of ytterbocenes. The reaction of the unsubstituted IPy 2a with 1, either in THF or toluene, gives rise to the paramagnetic species Cp*Yb-2(III)(IPy)(center dot-) (3a) as a result of a formal one-electron oxidation of the Yb-II ion along with IPy reduction to a radical-anionic state. The reactions of 1 with substituted iminopyridines 2b-d, bearing aryl or hetero-aryl dangling arms on the 6 position of the pyridine ring occur in a non-coordinating solvent (toluene) only and afford coordination compounds of a formally divalent ytterbium ion, coordinated by neutral IPy ligands Cp*Yb-2(II)(IPy)(0) (3b-d). The X-ray diffraction studies revealed that 2a-c act as bidentate ligands; while the radical-anionic IPy in 3a chelates the Yb-III ion with both nitrogens, neutral IPy ligands in 3b and 3c participate in the metal coordination sphere through the pyridine nitrogen and O or S atoms from the furan or thiophene moieties, respectively. Finally, in complex 3d the neutral IPy ligand formally adopts a monodentate coordination mode. However, an agostic interaction between the Yb-II ion and an ortho C-H bond of the phenyl ring has been detected. Imino-nitrogens in 3b-d are not involved in the metal coordination. Variable temperature magnetic measurements on 3a are consistent with a multiconfigurational ground state of the Yb ion and suggest that the largest contribution arises from the 4f(13)-radical configuration. For complexes 3b and 3c the data of magnetic measurements are indicative of a Yb-II-closed shell ligand electronic distribution. Complex 3d is characterized by a complex magnetic behavior which does not allow for an unambiguous estimation of its electronic structure. The results are rationalized using DFT and CSSCF calculations. Unlike diazabutadiene analogues, 3a does not undergo a solvent mediated metalligand electron transfer and remains paramagnetic in THF solution. On the other hand, complexes 3b-d readily react with THF to afford 1 and free IPy 2b-d

Genome-wide sequence analyses of ethnic populations across Russia

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation. Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show allele frequency divergence from neighboring populations. Population genetics analyses revealed six phylogeographic partitions among indigenous ethnicities corresponding to their geographic locales. This study presents a characterization of population-specific genomic variation in Russia with results important for medical genetics and for understanding the dynamic population history of the world's largest country

[4,6-Di-<i>tert</i>-butyl-<i>N</i>-(2,6-Dimethylphenyl)-<i>o</i>-Amidophenolato][4,6-Di-<i>tert</i>-butyl-<i>N</i>-(2,6-Dimethylphenyl)-<i>o</i>-Iminobenzosemiquinolato](2,2′-Bipyridyl)Indium(III)

A six-coordinated indium(III) complex (APMe)(imSQMe)In(bipy) (1), bearing two types of redox-active ligands—mono- (imSQMe) and dianion (APMe) of 4,6-di-tert-butyl-N-(2,6-dimethylphenyl)-o-iminobenzoquinone and 2,2′-bipyridyl—was synthesized and characterized in detail. The intense, well-resolved ESR spectrum of 1 in dichloromethane solution clearly indicates the spin density delocalization between both AP and imSQ ligands. The UV-vis spectrum of 1 possesses an absorption band in the NIR region. The molecular structure of compound 1 was established by single-crystal X-ray diffraction analysis

Synthesis, structure and magnetic properties of the dinuclear complex [1,3-C6H4{NC(Ph)N(SiMe3)}2]3Dy2 coordinated by ansa-bis(amidinate) ligands with a m-phenylene linker

International audienc

Amido Analogues of Nonbent Lanthanide (II) and Calcium Metallocenes. Heterolytic Cleavage of π-Bond Ln–Carbazolyl Ligand Promoted by Lewis Base Coordination

International audienc

Investigation of the slow relaxation of the magnetization dynamics in homoleptic ene-diamido organodysprosium( iii ) complexes with K + /arene interactions

International audienceWe report the synthesis, structure and magnetic investigations of two new Dy 3+ homoleptic ate-complexes based on different ene-diamido ligands [K(THF)2][Dy(DAD 2R)2] (R = H (1), Me (2) DAD 2R = [2,6-iPr2C6H3N-CR=CR-NC6H3iPr2-2,6 showing K + /Arene interactions. Magnetic investigations reval that both compounds exhibit a zero-field Single-Molecule Magnetic relaxation mainly governed by a Raman process

Single-Molecule Magnet Behavior in Dy 3+ Half-Sandwich Complexes Based on Ene-Diamido and Cp* Ligands

International audienceWe report in this communication the synthesis, structure and magnetic investigations of two new half-sandwich complexes [Dy(DAD)Cp*(THF)] (1) and [Li(THF) 3 ][Dy(DAD)Cp*Cl] (2) (Cp* = C 5 Me 5 , DAD = [2,6-iPr 2 C 6 H 3 N-CMeCMe-NC 6 H 3 iPr2-2,6). Both compounds exhibit zero-field SMM behavior but distinct relaxation dynamics originating from difference in the arrangement of Cp* and DAD ligands. The anisotropic barrier for 1 is found one order of magnitude greater than for 2

Synthesis, structure and magnetic properties of tris(pyrazolyl)methane lanthanide complexes: effect of the anion on the slow relaxation of magnetization

International audienc

Synthesis, structure and magnetic properties of a series of Ln( iii ) complexes with radical-anionic iminopyridine ligands: effect of lanthanide ions on the slow relaxation of the magnetization

International audienc