Physical Sciences and Mathematics Commons^™

Probing Radical Pathways In Electrophilic Addition Of Halogens: Classical Vs. Bridged Intermediates, Lisa George, Aimable Kalume, Scott Reid

Chemistry Faculty Research and Publications

We examine radical mediated pathways in electrophilic addition to the simplest alkene, ethylene, where the structure of the radical intermediate has been extensively debated. Starting from the π-complex with a dihalogen, C₂H₄⋯I₂, isolated in an inert matrix, we initiate reaction by photolytically cleaving the I₂ bond. We succeed in trapping and spectroscopically interrogating the symmetrically bridged radical complex, which calculations confirm is the global minimum on the C₂H₅I Potential Energy Surface (PES). Consistent with the participation of a bridged intermediate, radical addition preferentially but not exclusively yields the anti …

Spectral Data For "Reactivity Of Acyclic (Pentadienyl)Iron(1+) Cations: Synthetic Studies Directed Toward The Frondosins", Do W. Lee, Rajesh K. Pandey, Sergey V. Lindeman, William A. Donaldson

Natural Products Synthesis via Organoiron Methodology

Spectral data created in the course of the research project. Supports specific findings in "Reactivity of acyclic (pentadienyl)iron(1+) cations: Synthetic studies directed toward the frondosins".

A short, 4-step route to the scaffold of frondosin A and B is reported. The [1-methoxycarbonyl-5-(2′,5′-dimethoxyphenyl)pentadienyl]Fe(CO)₃⁺ cation was prepared in two steps from (methyl 6-oxo-2,4-hexadienoate)Fe(CO)₃. Reaction of this cation with isopropenyl Grignard or cyclohexenyllithium reagents affords (2-alkenyl-5-aryl-1-methoxycarbonyl-3-pentene-1,5-diyl)Fe(CO)₃ along with other addition products. Oxidative decomplexation of these (pentenediyl)iron complexes, utilizing CuCl₂, affords 6-aryl-3-methoxycarbonyl-1,4-cycloheptadienes via the presumed intermediacy of a cis-divinylcyclopropane.

On Pi-Stacking, Ch/Pi, And Halogen Bonding In Halobenzene Clusters: Resonant 2-Photon Ionization Studies Of Chlorobenzene, Lloyd Muzangwa, Silver Nyambo, Brandon Uhler, Scott Reid

Chemistry Faculty Research and Publications

Noncovalent interactions such as hydrogen bonding, π-π stacking, CH/π interactions, and halogen bonding play crucial roles in a broad spectrum of chemical and biochemical processes, and can exist in cooperation or competition. Here we report studies of the homoclusters of chlorobenzene, a prototypical system where π-π stacking, CH/π interactions, and halogen bonding interactions may all be present. The electronic spectra of chlorobenzene monomer and clusters (Clbz)_n with n = 1-4 were obtained using resonant 2-photon ionization in the origin region of the S₀–S₁ (ππ*) state of the monomer. The cluster spectra show in all cases a …

Electronic Communication Across Diamagnetic Metal Bridges: A Homoleptic Gallium(Iii) Complex Of A Redox-Active Diarylamido-Based Ligand And Its Oxidized Derivatives, Brendan J Liddle, Sarath Wanniarachchi, Jeewantha S. Hewage, Sergey Lindeman, Brian Bennett, James R. Gardinier

Chemistry Faculty Research and Publications

Complexes with cations of the type [Ga(L)₂]ⁿ⁺ where L = bis(4-methyl-2-(1H-pyrazol-1-yl)phenyl)amido and n = 1, 2, 3 have been prepared and structurally characterized. The electronic properties of each were probed by electrochemical and spectroscopic means and were interpreted with the aid of density functional theory (DFT) calculations. The dication, best described as [Ga(L^–)(L⁰)]²⁺, is a Robin-Day class II mixed-valence species. As such, a broad, weak, solvent-dependent intervalence charge transfer (IVCT) band was found in the NIR spectrum in the range 6390–6925 cm^–1, depending on the solvent. Band shape …

On The Electronic Spectroscopy Of The Iso-Polyhalomethanes, Aimable Kalume, Lisa George, Scott Reid

Chemistry Faculty Research and Publications

The iso-polyhalomethanes are important reactive intermediates, displaying intense near-UV absorption bands that have been assigned to the S₀ → S₃ transition on the basis of Time-Dependent Density Functional Theory (TDDFT) calculations. In this work, theory and multi-dimensional Franck–Condon (FC) analysis are used to model the electronic spectra of selected iso-polyhalomethanes. The S₀ → S₃ transition approximately corresponds to a π–π^∗ transition on the halocarbocation subunit, which induces significant geometry changes. The calculated multimode FC profiles capture features of the experimental spectra of the matrix-isolated species, and are compared with the results of previous Resonance Raman …

G-Cimp Status Prediction Of Glioblastoma Samples Using Mrna Expression Data, Mehmet Baysan, Serdar Bozdag, Margaret C. Cam, Svetlana Kotliarova, Susie Ahn, Jennifer Walling, Jonathan K. Killian, Holly Stevenson, Paul Meltzer, Howard A. Fine

Mathematics, Statistics and Computer Science Faculty Research and Publications

Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure. The dramatic molecular and clinical heterogeneity seen in this tumor has led to attempts to define genetically similar subgroups of GBM with the hope of developing tumor specific therapies targeted to the unique biology within each of these subgroups. Recently, a subset of relatively favorable prognosis GBMs has been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberrations, DNA methylation patterns, and (mRNA) expression profiles compared to other GBMs. While the standard method for identifying G-CIMP tumors is based on …

Spectroscopic And Computational Studies Of Matrix-Isolated Iso-Cxbr3 (X=F,Cl,Br): Structure, Properties, And Photochemistry Of Substituted Iso-Tribromomethanes, Lisa George, Aimable Kalume, Scott Reid, Brian J. Esselman, Robert J. Mcmahon

Chemistry Faculty Research and Publications

Iso-polyhalomethanes are important reactive intermediates in the condensed and gas-phase chemistry of halomethanes. Building upon our recent study of iso-bromoform, in this work the substituted iso-tribromomethanes (iso-CXBr₃; X = F, Cl, Br) were characterized by matrix isolation infrared and UV/Vis spectroscopy, supported by ab initio calculations, to further probe the structure, spectroscopy, properties, and photochemistry of these important intermediates. Selected wavelength laser irradiation of CXBr₃ samples in an inert rare gas (typically Ar; mixing ratio 1:500) held at ∼5 K yielded iso-CXBr₃ (XBrC–Br–Br or Br₂C–Br–X). The observed infrared and UV/Vis absorptions are in excellent …

Syntheses And Electronic Properties Of Rhodium(Iii) Complexes Bearing A Redox-Active Ligand, Sarath Wanniarachchi, Brendan J Liddle, Brandon Kizer, Jeewantha S. Hewage, Sergey Lindeman, James R. Gardinier

Chemistry Faculty Research and Publications

A series of rhodium(III) complexes of the redox-active ligand, H(L = bis(4-methyl-2-(1H-pyrazol-1-yl)phenyl)amido), was prepared, and the electronic properties were studied. Thus, heating an ethanol solution of commercial RhCl3·3H2O with H(L) results in the precipitation of insoluble [H(L)]RhCl3, 1. The reaction of a methanol suspension of [H(L)]RhCl3 with NEt4OH causes ligand deprotonation and affords nearly quantitative yields of the soluble, deep-green, title compound (NEt4)[(L)RhCl3]·H2O, 2·H2O. Complex 2·H2O reacts readily with excess pyridine, triethylphosphine, or pyrazine (pyz) to eliminate NEt4Cl and give charge-neutral complexes trans-(L)RhCl2(py), trans-3, trans-(L)RhCl2(PEt3), trans- 4, or trans-(L)RhCl2(pyz), trans-5, where the incoming Lewis base is trans- to the amido …

Structural, Spectroscopic, And Electrochemical Properties Of Nonheme Fe(Ii)-Hydroquinonate Complexes: Synthetic Models Of Hydroquinone Dioxygenases, Amanda E. Baum, Heaweon Park, Denan Wang, Sergey Lindeman, Adam T. Fiedler

Chemistry Faculty Research and Publications

Using the tris(3,5-diphenylpyrazol-1-yl)borate (^Ph2Tp) supporting ligand, a series of mono- and dinuclear ferrous complexes containing hydroquinonate (HQate) ligands have been prepared and structurally characterized with X-ray crystallography. The monoiron(II) complexes serve as faithful mimics of the substrate-bound form of hydroquinone dioxygenases (HQDOs) – a family of nonheme Fe enzymes that catalyze the oxidative cleavage of 1,4-dihydroxybenzene units. Reflecting the variety of HQDO substrates, the synthetic complexes feature both mono- and bidentate HQate ligands. The bidentate HQates cleanly provide five-coordinate, high-spin Fe(II) complexes with the general formula [Fe(^Ph2Tp)(HL^X)] (1X), where HL^X is …

The Sense-Isomorphism Theoretical Image Voxel Estimation (Sense-Itive) Model For Reconstruction And Observing Statistical Properties Of Reconstruction Operators, Iain P. Bruce, M. Muge Karaman, Daniel B. Rowe

Mathematics, Statistics and Computer Science Faculty Research and Publications

The acquisition of sub-sampled data from an array of receiver coils has become a common means of reducing data acquisition time in MRI. Of the various techniques used in parallel MRI, SENSitivity Encoding (SENSE) is one of the most common, making use of a complex-valued weighted least squares estimation to unfold the aliased images. It was recently shown in Bruce et al. [Magn. Reson. Imag. 29(2011):1267-1287] that when the SENSE model is represented in terms of a real-valued isomorphism,it assumes a skew-symmetric covariance between receiver coils, as well as an identity covariance structure between voxels. In this manuscript, we show …

On Lattices Of Varieties Of Restriction Semigroups, Peter R. Jones

Mathematics, Statistics and Computer Science Faculty Research and Publications

The left restriction semigroups have arisen in a number of contexts, one being as the abstract characterization of semigroups of partial maps, another as the ‘weakly left E-ample’ semigroups of the ‘York school’, and, more recently as a variety of unary semigroups defined by a set of simple identities. We initiate a study of the lattice of varieties of such semigroups and, in parallel, of their two-sided versions, the restriction semigroups. Although at the very bottom of the respective lattices the behaviour is akin to that of varieties of inverse semigroups, more interesting features are soon found in the …

Chemical Proteomics-Based Analysis Of Off-Target Binding Profiles For Rosiglitazone And Pioglitazone: Clues For Assessing Potential For Cardiotoxicity, Brian R. Hoffmann, Mohamed F. El-Mansy, Daniel S. Sem, Andrew S. Greene

Chemistry Faculty Research and Publications

Drugs exert desired and undesired effects based on their binding interactions with protein target(s) and off-target(s), providing evidence for drug efficacy and toxicity. Pioglitazone and rosiglitazone possess a common functional core, glitazone, which is considered a privileged scaffold upon which to build a drug selective for a given target—in this case, PPARγ. Herein, we report a retrospective analysis of two variants of the glitazone scaffold, pioglitazone and rosiglitazone, in an effort to identify off-target binding events in the rat heart to explain recently reported cardiovascular risk associated with these drugs. Our results suggest that glitazone has affinity for dehydrogenases, consistent …

Experimental Documentation Of The Structural Consequences Of Hydrogen-Bonding Interactions To The Proximal Cysteine Of A Cytochrome P450, Piotr J. Mak, Yuting Yang, Sangchoul Im, Lucy A. Waskell, James R. Kincaid

Chemistry Faculty Research and Publications

Resonance Raman spectroscopy is used to document, for the first time, a 6 cm−1 decrease of the Fe-S stretch by introducing an H-bond donor into the proximal pocket of a cytochrome P450, which interacts with the key cysteine thiolate axial ligand. The anticipated trans-effect on bound exogenous ligands is also confirmed and evidence is obtained supporting intimate interaction of the new histidyl-imidazole fragment with the heme periphery.

Fe(Ii) Complexes That Mimic The Active Site Structure Of Acetylacetone Dioxygenase: O2 And No Reactivity, Heoweon Park, Michael M. Bittner, Jacob Baus, Sergey Lindeman, Adam T. Fiedler

Chemistry Faculty Research and Publications

Acetylacetone dioxygenase (Dke1) is a bacterial enzyme that catalyzes the dioxygen-dependent degradation of β-dicarbonyl compounds. The Dke1 active site contains a nonheme monoiron(II) center facially ligated by three histidine residues (the 3His triad); coordination of the substrate in a bidentate manner provides a five-coordinate site for O₂ binding. Recently, we published the synthesis and characterization of a series of ferrous β-diketonato complexes that faithfully mimic the enzyme–substrate intermediate of Dke1 (Park, H.; Baus, J.S.; Lindeman, S.V.; Fiedler, A.T. Inorg. Chem.2011, 50, 11978–11989). The 3His triad was modeled with three different facially coordinating N3 supporting ligands, and …

H-Coloring Tori, John Engbers, David Galvin

Mathematics, Statistics and Computer Science Faculty Research and Publications

For graphs G and H, an H-coloring of G is a function from the vertices of G to the vertices of H that preserves adjacency. H-colorings encode graph theory notions such as independent sets and proper colorings, and are a natural setting for the study of hard-constraint models in statistical physics. We study the set of H-colorings of the even discrete torus View the MathML source, the graph on vertex set {0,…,m−1}d (m even) with two strings adjacent if they differ by 1 (mod m) on one coordinate and agree on all others. This is a bipartite graph, with bipartition …

Mathematical Problem Posing As A Measure Of Curricular Effect On Students' Learning, Jinfa Cai, John Moyer, Ning Wang, Stephen Hwang, Bikai Nie, Tammy Garber

Mathematics, Statistics and Computer Science Faculty Research and Publications

In this study, we used problem posing as a measure of the effect of middle-school curriculum on students' learning in high school. Students who had used a standards-based curriculum in middle school performed equally well or better in high school than students who had used more traditional curricula. The findings from this study not only show evidence of strengths one might expect of students who used the standards-based reform curriculum but also bolster the feasibility and validity of problem posing as a measure of curriculum effect on student learning. In addition, the findings of this study demonstrate the usefulness of …

On Order Statistics For Gs-Distributions, M. M. Mohie El-Din, M. M. Amein, Gholamhossein Hamedani

Mathematics, Statistics and Computer Science Faculty Research and Publications

In this article, a class of distributions is used to establish several recurrence relations satisfied by single and product moments of order statistics and progressive Type-II right censoring. The recurrence relations for moments of some specific distributions including uniform (a;b); exponential (λ); generalized exponential (α;λ;ν); beta (1;b); beta (b;1); logistic (α;β) and other distributions from order statistics and progressive Type-II right censoring can be obtained as special cases. A short explanation of GS-distribution can be found in reference [27]. As an example, means, variances and covariances for standard exponential distribution of progressive Type-II right censored order statistics are computed. Various …

Analyzing Multiple-Probe Microarray: Estimation And Application Of Gene Expression Indexes, Mehdi Maadooliat, Jianhua Z. Huang, Jianhua Hu

Mathematics, Statistics and Computer Science Faculty Research and Publications

Gene expression index estimation is an essential step in analyzing multiple probe microarray data. Various modeling methods have been proposed in this area. Amidst all, a popular method proposed in Li and Wong (2001) is based on a multiplicative model, which is similar to the additive model discussed in Irizarry et al. (2003a) at the logarithm scale. Along this line, Hu et al. (2006) proposed data transformation to improve expression index estimation based on an ad hoc entropy criteria and naive grid search approach. In this work, we re-examined this problem using a new profile likelihood-based transformation estimation approach that …

The Fe-Type Nitrile Hydratase From Comamonas Testosteroni Ni1 Does Not Require An Activator Accessory Protein For Expression In Escherichia Coli, Misty L. Kuhn, Salette Martinez, Natalie Gumataotao, Uwe Bornscheuer, Dali Liu, Richard C. Holz

Chemistry Faculty Research and Publications

We report herein the functional expression of an Fe-type nitrile hydratase (NHase) without the co-expression of an activator protein or the Escherichia coli chaperone proteins GroES/EL. Soluble protein was obtained when the α- and β-subunit genes of the Fe-type NHase Comamonas testosteroni Ni1 (CtNHase) were synthesized with optimized E. coli codon usage and co-expressed. As a control, the Fe-type NHase from Rhodococcus equi TG328–2 (ReNHase) was expressed with (ReNHase^+Act) and without (ReNHase^−Act) its activator protein, establishing that expression of a fully functional, metallated ReNHase enzyme requires the …

Spectroelectrochemical Elucidation Of The Kinetics Of Two Closely Spaced Electron Transfers, Robert L. Keesey, Michael D. Ryan

Chemistry Faculty Research and Publications

The use of spectroelectrochemistry to facilitate the analysis of an EE mechanism was reported in this work. Using a set of spectra as a function of potential, the spectra of all three oxidation states were determined using evolving window factor analysis. From these spectra, the concentration of each species in solution was determined for each potential. Using these data, the current was calculated. Unlike the direct measurement of current, the current due to each redox process was determined, allowing one to analyze each redox process separate from the other. With the use of the Butler–Volmer equation, the redox potential and …

Bayesian Analysis Of Hypothesis Testing Problems For General Population: A Kullback–Leibler Alternative, Naveen K. Bansal, Gholamhossein Hamedani, Ru Sheng

Mathematics, Statistics and Computer Science Faculty Research and Publications

We consider a hypothesis problem with directional alternatives. We approach the problem from a Bayesian decision theoretic point of view and consider a situation when one side of the alternatives is more important or more probable than the other. We develop a general Bayesian framework by specifying a mixture prior structure and a loss function related to the Kullback–Leibler divergence. This Bayesian decision method is applied to Normal and Poisson populations. Simulations are performed to compare the performance of the proposed method with that of a method based on a classical z-test and a Bayesian method based on the …

Involvement Of Microrna Families In Cancer, Stefan Wuchty, Dolores Arjona, Serdar Bozdag, Peter O. Bauer

Mathematics, Statistics and Computer Science Faculty Research and Publications

Collecting representative sets of cancer microRNAs (miRs) from the literature we show that their corresponding families are enriched in sets of highly interacting miR families. Targeting cancer genes on a statistically significant level, such cancer miR families strongly intervene with signaling pathways that harbor numerous cancer genes. Clustering miR family-specific profiles of pathway intervention, we found that different miR families share similar interaction patterns. Resembling corresponding patterns of cancer miRs families, such interaction patterns may indicate a miR family’s potential role in cancer. As we find that the number of targeted cancer genes is a naı¨ve proxy for a cancer …

Structural Characterization Of Zn(Ii)-, Co(Ii)-, And Mn(Ii)-Loaded Forms Of The Arge-Encoded N-Acetyl-L-Ornithine Deacetylase From Escherichia Coli, Ye Tao, Jacob E. Shokes, Wade C. Mcgregor, Robert A. Scott, Richard C. Holz

Chemistry Faculty Research and Publications

The Zn, Co, and Mn K-edge extended X-ray absorption fine structure (EXAFS) spectra of the N-acetyl-l-ornithine deacetylase (ArgE) from Escherichia coli, loaded with one or two equivalents of divalent metal ions (i.e., [Zn(II)_(ArgE)], [Zn(II)Zn(II)(ArgE)], [Co(II)_(ArgE)], [Co(II)Co(II)(ArgE)], [Mn(II)_(ArgE)], and [Mn(II)Mn(II)(ArgE)]), were recorded. The Fourier transformed data (FT) for [Zn(II)_(ArgE)], [Zn(II)Zn(II)(ArgE)], [Co(II)_(ArgE)] and [Co(II)Co(II)(ArgE)] are dominated by a peak at 2.05 Å, that can be fit assuming five or six light atom (N,O) scatterers. Inclusion of multiple-scattering contributions from the outer-shell atoms of a histidine-imidazole ring resulted in reasonable Debye–Waller factors for these contributions and a slight reduction …

Simplified Models Of Vector Control Impact Upon Malaria Transmission By Zoophagic Mosquitoes, Samson S. Kiware, Nakul Chitnis, Sarah J. Moore, Gregor J. Devine, Silas Majambere, Stephen Merrill, Gerry F. Killeen

Mathematics, Statistics and Computer Science Faculty Research and Publications

Background

High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as “very zoophagic,” meaning they feed occasionally (

Methods and Findings

We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index). The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1) Rely on only three field-measurable parameters. (2) Predict immediate and delayed (with …

Sprectral Data For "Generation Of Molecular Complexity From Cyclooctatetraene Using Dienyliron And Olefin Metathesis", Mohamed F. El-Mansy, Anobick Sar, Subhabrata Chaudhury, Nathaniel J. Wallock, William A. Donaldson

Natural Products Synthesis via Organoiron Methodology

Spectral data used in the course of researching "Generation of molecular complexity from cyclooctatetraene using dienyliron and olefin metathesis methodology".

Transformation of the simple hydrocarbon cyclooctatetraene into a variety of polycyclic skeletons was achieved by sequential coordination to iron, reaction with electrophiles followed by allylated nucleophiles, decomplexation and olefin metathesis.

Genomic Analysis Of Immune Response Against Vibrio Cholerae Hemolysin In Caenorhabditis Elegans, Surasri N. Sahu, Jada Lewis, Isha Patel, Serdar Bozdag, Jeong H. Lee, Joseph E. Leclerc, Hediye Nese Cinar

Mathematics, Statistics and Computer Science Faculty Research and Publications

Vibrio cholerae cytolysin (VCC) is among the accessory V. cholerae virulence factors that may contribute to disease pathogenesis in humans. VCC, encoded by hlyA gene, belongs to the most common class of bacterial toxins, known as poreforming toxins (PFTs). V. cholerae infects and kills Caenorhabditis elegans via cholerae toxin independent manner. VCC is required for the lethality, growth retardation and intestinal cell vacuolation during the infection. However, little is known about the host gene expression responses against VCC. To address this question we performed a microarray study in C. elegans exposed to V. cholerae strains with intact and deleted hlyA …

On The Electronic Spectroscopy Of Closed Shell Cations Derived From Resonance Stabilized Radicals: Insights From Theory And Franck-Condon Analysis, T. P. Troy, S. H. Kable, T. W. Schmidt, Scott Reid

Chemistry Faculty Research and Publications

Context. Recent attention has been directed on closed-shell aromatic cations as potential carriers of the diffuse interstellar bands. The spectra of mass-selected, matrix-isolated benzylium, and tropylium cations were recently reported. The visible spectrum of benzylium exhibits a large Franck-Condon (FC) envelope, inconsistent with diffuse interstellar band carriers.

Aims. We perform a computational analysis of the experimentally studied benzylium spectrum before extending the methods to a range of larger, closed-shell aromatic cations to determine the potential for this class of systems as diffuse interstellar band carriers.

Methods. Density functional theory (DFT), time-dependent ((TD)DFT), and multi-configurational self-consistent field second-order perturbation theory (MRPT2) …

Generation Of Molecular Complexity From Cyclooctatetraene Using Dienyliron And Olefin Metathesis Methodology, Mohamed F. El-Mansy, Anobick Sar, Subhabrata Chaudhury, Nathaniel J. Wallock, William A. Donaldson

Chemistry Faculty Research and Publications

Transformation of the simple hydrocarbon cyclooctatetraene into a variety of polycyclic skeletons was achieved by sequential coordination to iron, reaction with electrophiles followed by allylated nucleophiles, decomplexation and olefin metathesis.

H-Colouring Bipartite Graphs, John Engbers, David Galvin

Mathematics, Statistics and Computer Science Faculty Research and Publications

For graphs G and H, an H-colouring of G (or homomorphism from G to H) is a function from the vertices of G to the vertices of H that preserves adjacency. H-colourings generalize such graph theory notions as proper colourings and independent sets. For a given H, k∈V(H) and G we consider the proportion of vertices of G that get mapped to k in a uniformly chosen H-colouring of G. Our main result concerns this quantity when G is regular and bipartite. We find numbers 0⩽a−(k)⩽a+(k)⩽1 with the property that for all such G, with high probability the proportion is …

Human Gene Copy Number Spectra Analysis In Congenital Heart Malformations, Aoy Tomita-Mitchell, Donna K. Mahnke, Craig Struble, Maureen E. Tuffnell, Karl D. Stamm, Mats Hidestrand, Susan Harris, Mary A. Goetsch, Pippa Simpson, David P. Bick, Ulrich Broeckel, Andrew N. Pelech, James S. Tweddell, Michael Mitchell

Mathematics, Statistics and Computer Science Faculty Research and Publications

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 …