bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of replication studies, combined data analysis, and analytical methods in complex diseases
Authors: Xu Jianfeng , Wiesch Denise G. , Taylor Eugene W. , Meyers Deborah A. 
Published: November 2013

AbstractDue to genetic heterogeneity, phenocopies, incomplete penetrance, misdiagnosis, and unknown mode of inheritance, linkage studies of most complex diseases are unlikely to provide conclusive findings with unambiguously high lod scores. Typically, several marginally significant lod scores or elevated lod scores are observed in a genome‐wide screen. However, it is usually difficult to differentiate these findings from false positives (type I errors). Two approaches are commonly used to guard against false positives: replication studies in independent samples and combined data analysis. In the current paper, we evaluated these two common approaches using simulated data where data from multiple groups were available and locations of disease genes were known. We found replication studies and combined data analysis performed similarly in terms of their ability to identify true and false positive linkages. Both approaches confirmed two true linkages and did not confirm any false positive linkages. The results also indicated that it is not appropriate to apply the criteria proposed for confirming significant evidence for linkage to confirm regions with only suggestive evidence for linkage. The current results support previous findings that parametric analysis using an incorrect genetic model can still identify a true linkage.
Comparison of empirical strategies to maximize GENEHUNTER lod scores
Authors: Chen Chien H. , Finch Stephen J. , Mendell Nancy R. , Gordon Derek 
Published: November 2013

AbstractWe compare four strategies for finding the settings of genetic parameters that maximize the lod scores reported in GENEHUNTER 1.2. The four strategies are iterated complete factorial designs, iterated orthogonal Latin hypercubes, evolutionary operation, and numerical optimization. The genetic parameters that are set are the phenocopy rate, penetrance, and disease allele frequency; both recessive and dominant models are considered. We selected the optimization of a recessive model on the Collaborative Study on the Genetics of Alcoholism (COGA) data of chromosome 1 for complete analysis. Convergence to a setting producing a local maximum required the evaluation of over 100 settings (for a time budget of 800 minutes on a Pentium II 300 MHz PC). Two notable local maxima were detected, suggesting the need for a more extensive search before claiming that a global maximum had been found. The orthogonal Latin hypercube design was the best strategy for finding areas that produced high lod scores with small numbers of evaluations. Numerical optimization starting from a region producing high lod scores was the strategy that found the highest maximum observed.
Monte carlo markov chain methods for genome screening
Authors: Daw E.W. , Kumm J. , Snow G.L. , Thompson E.A. , Wijsman E.M. 
Published: November 2013

AbstractWe used Monte Carlo Markov chain (MCMC) methods to analyze a quantitative trait, MAO level, and a discrete trait, Collaborative Study on the Genetics of Alcoholism (COGA) alcoholism. Segregation, linkage, and haplotype sharing were analyzed and effects of marker map features were examined. For MAO, modest signals were found on chromosomes 1 and 17 for raw data, and 15 for covariate‐adjusted data. For alcoholism, a strong signal was found on chromosome 1 with modest signals on chromosomes 4 and 10.
Comparison of two linkage inference procedures for genes related to the P300 component of the event related potential
Authors: Goldin Lynn R. , Chase Gary A. 
Published: November 2013

AbstractOur goal was to detect genes contributing to the P300 component of the event related potential (ERP). We found that all of the ERP traits were highly correlated. Most of them distinguished alcoholics from nonalcoholics. To have one summary variable for the ERP traits, we calculated the first principal component (PRIN1). After adjusting for age and sex, we screened for linkage of PRIN1 to all of the markers using the two‐point Haseman‐Elston sib‐pair test. We compared results obtained from computing a moving average of two‐point p‐values (“regional” inference) in an approximately 10 cM region with those obtained from single, two‐point tests. Different “suggestive” and “significant” linkage regions were found using the two methods. Based on the regional method, areas on chromosomes 2 and 5 should be followed up in future studies.
An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation
Authors: Iturria Stephen J. , Williams Jeff T. , Almasy Laura , Dyer Thomas D. , Blangero John 
Published: November 2013

AbstractWe propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.
Sib‐pair analysis of the collaborative study on the genetics of alcoholism data set
Authors: Jorgenson Eric , Hinds David , Risch Neil 
Published: November 2013

AbstractNonparametric sib‐pair analysis was performed on the Collaborative Study on the Genetics of Alcoholism data set. Concordant and discordant pair groups were examined using the ASPEX package of programs. Allele sharing and multipoint lod scores for six comparison groups were obtained. Sharing and lod score patterns were not consistent with a simple genetic interpretation.
Searching for alcoholism susceptibility genes using markov chain monte carlo methods
Authors: Leal Suzanne M. , Heath Simon C. 
Published: November 2013

AbstractMarkov chain Monte Carlo (MCMC) methods offer a rapid parametric approach that can test for linkage throughout the entire genome. It has an advantage similar to nonparametric methods in that the model does not have to be completely specified a priori. However, unlike nonparametric methods, there are no limitations on pedigree size and MCMC methods can also handle relatively complex pedigree structures. In addition MCMC methods can be used to carry segregation analysis in order to answer questions on the genetic components of a disease phenotype. Segregation analysis gave evidence for between two and eight alcoholism susceptibility loci, each having a modest effect on the phenotype. MCMC methods were used to map alcoholism loci using the phenotypes ALDX1 (DSM‐III‐R and Feighner criteria) and ALDX2 (World Health Organization diagnosis ICD‐10 criteria). There was mild evidence for quantitative trait loci on chromosomes 2,10, and 11.
Identifying influential individuals in linkage analysis: Application to a quantitative trait locus detected in the COGA data
Authors: Mitchell Braxton D. , Ghosh Soumitra , Watanabe Richard M. , Slifer Susan H. , Hsueh Wen‐Chi , Birznieks Gunther 
Published: November 2013

AbstractOnce linkage is detected to a quantitative trait locus (QTL), the next step towards localizing the gene involved may be to identify those families, or individuals, in whom the putative mutations are segregating. In this paper, we describe a jackknife procedure for identifying individuals (and families) who contribute disproportionately to the linkage. Following initial detection of linkage to a QTL, the strategy involves sequentially removing each individual (or each family) from the analysis and recomputing the lod score associated with the linked region using data from all remaining subjects (or families). This procedure can be used to determine if particular observations have substantial impact on evidence for linkage. Identification of such observations may provide insights for further efforts to localize the QTL.
Structural decomposition of genetic diversity in families with alcoholism
Authors: Stassen Hans H. , Begleiter Henri , Porjesz Bernice , Rice John , Scharfetter Christian , Reich Theodore 
Published: November 2013

AbstractUsing genotypes of 280 marker loci on the 22 autosomes of 105 alcohol‐dependent probands, their affected and unaffected sibs, as well as their parents, we iteratively constructed a genetic similarity function that enabled us to quantify the interindividual genetic distances d(xixj) between feature vectors xi,xjmade up by the allelic patterns of individuals i, j with respect to loci 11 12, …, 1n. Based on this similarity function, we investigated the sib‐sib similarities that are expected to deviate from “0.5” in affected sib pairs if the region of interest contains markers close to disease‐causing genes. The reference value “0.5” was derived from the parents‐offspring similarities, because these are independent of the affection status. The question of population admixture was addressed by means of multivariate structural analyses. These analyses led to four “natural” groups whose validity was tested through the father‐mother similarities. Additionally, we determined the eigenvectors that optimally represented the genetic variation and found several marker configurations on chromosomes 1, 3, 7, 15, and 17 that reproducibly discriminated (p ≤ 0.01) affected probands/sibs from unaffected sibs, while no such differences were found between affected probands and affected sibs.
Whole genome association studies for genes affecting alcohol dependence
Authors: Sun Fengzhu , Cheng Rong , Flanders W. Dana , Yang Quanhe , Khoury Muin J. 
Published: November 2013

AbstractWe applied the transmission/disequilibrium test (TDT) for sibs (S‐TDT) and for families with one parent (1‐TDT), to the Collaborative Study on the Genetics of Alcoholism data set. The combined test is used to screen the whole genome to locate genes responsible for alcohol dependence. This analysis supports the previous finding that the region close to GABRB1 on chromosome 4 might be associated with alcohol dependence. The regions close to D6S474 and D11S1998 are also of particular interest. We found segregation distortion at the GR1K1 locus. The segregation distortion might be due to the binning method used in genotyping at this locus.
Application of an ordered subset analysis approach to the genetics of alcoholism
Authors: Watanabe Richard M. , Ghosh Soumitra , Birznieks Gunther , Duren William L. , Mitchell Braxton D. 
Published: November 2013

AbstractFor complex diseases, underlying etiologic heterogeneity may reduce power to detect linkage. Thus, methods to identify more homogeneous subgroups within a given sample in a linkage study may improve detection of putative susceptibility loci. In this study we describe an ordered subsetting approach that utilizes disease‐related quantitative trait data to complement traditional linkage analysis. This approach uses family‐based lod scores derived from the initial genome screen and a family‐based descriptor of the trait of interest. The goal of the approach is to identify more homogeneous subgroups of the data by ranking families based on their quantitative trait data. Permutation testing is used to assess statistical significance. This approach can be adapted to a variety of linkage methods and may provide a means to dissect some of the underlying heterogeneity in complex disease genetics.
Parental sex effect in families with alcoholism
Authors: Wyszynski Diego F. , Panhuysen Carolien I. M. 
Published: November 2013

AbstractParental sex effects have been shown to influence the inheritance of a number of complex disorders. In this paper we performed affected sib‐pair analyses on 105 families with recurrent alcoholism to evaluate the effects that the parent of origin might have on this disorder. Three alternative classification schemes were used and the families were grouped as maternal, paternal, mixed, or unknown. Paternal effects were observed at D9S64, D16S475, and D16S2622, while maternal effects were expressed at FABP2, D8S280, D8S1715, and D8S1988. Except for D16S2622, none of these markers resulted in a significant p‐value when all families were analyzed together. These results suggest that the parental sex should not be ignored and that a discriminatory analysis should always be performed.
Summary of analyses of problem 2 simulated data for GAW11
Authors: Greenberg D.A. 
Published: November 2013

AbstractThe simulated data for Problem 2 of the 11th Genetic Analysis Workshop (GAW11) consisted of family linkage data and disease data from three populations, each population with different genetic parameters. The disease was simulated such that there were two genetically distinct diseases, one caused by a single locus with three alleles and the other by two epistatically interacting loci. The two diseases were clinically identical. Each of the diseases had a severe and mild form. One of the diseases was influenced by an environmental factor and one by an allele at one of the marker loci (association). Linkage data consisted of 300 polymorphic markers. Investigators analyzed these data in a myriad of ways, using most currently available linkage techniques and association analysis methods. In addition, investigators also tested newly developed methods, some of which took advantage of the existence of the environmental component. Other types of analyses included meta‐analyses, methods of combining data from different studies, questions of replication, how much information is available in a single data set, and analyses for gene×gene and gene×environment interaction.
Genetic analysis of a complex disease in the presence of an environmental risk factor
Authors: Eichenbaum‐Voline Sophie , Baur Max P. , Knapp Michael 
Published: November 2013

AbstractThe role of a gene in a disease may be hidden by the presence of another risk factor such as an environmental factor. In that case, stratifying the data according to this factor strengthens power to detect linkage or association. We followed this strategy on the simulated data provided by GAW11. The transmission/disequilibrium test (TDT) and the maximum likelihood score (MLS) were performed on the first replicate of 100 sib pairs from the population in which the disease risk was significantly influenced by an environmental factor (E1). However, only the TDT was powerful enough to detect one of the four loci involved in the genetic determination of the disease. The MLS showed no evidence for linkage after taking into account the fact that multiple tests were performed. Even when stratifying the sample according to the presence of E1, no additional loci could be detected. Given the simulated models, 100 sib pairs are too low a sample size for a systematic screening of the genome, which in this case was an analysis of 300 markers.
Meta‐analysis by combining parameter estimates: Simulated linkage studies
Authors: Goldstein Darlene R. , Sain Stephan R. , Guerra Rudy , Etzel Carol J. 
Published: November 2013

AbstractSeveral meta‐analytic techniques have been developed for combining information from multiple studies in contexts other than linkage detection. We apply the technique of combining parameter estimates to the problem of finding disease loci in the simulated data and compare results with those obtained by reanalyzing pooled raw data. To facilitate the combination of study results, we highly recommend that parameter estimates and their standard errors be reported in published studies. If different research groups were to make original data available, progress toward disease gene location and characterization may be more quickly made.
Liquid Junction Potentials and Transference Numbers in Montmorillonite Suspensions
Authors: Shainberg I. , Caiserman A. 
Published: November 2013

AbstractThe EMF's of concentration cells with and without transference were determined. The cells consist of two compartments each containing an equal concentration of K‐montmorillonite with a different KCl concentration at the two sides of the liquid junction. The EMF's were determined with Ag/AgCl electrodes and a K‐sensitive glass electrode. The liquid junction potential and the transference number of the ionic species in the suspensions were calculated from the data of the EMF. The liquid junction potential (being zero for KCl solution), and the transference number of K+, were found to increase with the increase in the clay concentration. This indicates that pH measurements in clay suspensions involve a liquid junction at the KCl bridge which cannot be disregarded.
Electron Microscopic and Kinetic Study of the Flocculation of Calcium Montmorillonite
Authors: Fitzsimmons R. F. , Posner A. M. , Quirk J. P. 
Published: November 2013

AbstractElectron microscope studies have shown that calcium montmorillonite, originally dispersed into separate platelets, flocculates with time to form large flat sheet‐like particles which exhibit pronounced flow birefringence. Although kinetic studies indicate for rapid salt flocculation face to face condensation is unlikely to occur, it has been shown that with long times in electrolyte free systems a small amount of perpendicular stacking occurs, resulting in the development of particles four layers thick. During the same period the sodium montmorillonite suspension remains unchanged. Lateral growth of the particles is most likely brought about by an intermediate orientation of the particles with overlapping of the edges of the particles, so that they link together to form a flat sheet. These results prove that in suspension calcium montmorillonite quasi crystals definitely have different dimensions from the original sodium montmorillonite. Kinetic and electron microscope studies of salt flocculated calcium montmorillonite systems indicate that the salt floccules consist of particles randomly oriented relative to one another. However electron microscope studies show that salt floccules may undergo rearrangements, depending on their treatment, resulting in a greater ordering of individual particles. Dialysis of the salt flocculated system leads to birefringent units similar to those formed in the absence of salt. Further stacking and lateral growth is induced by drying. These results explain the very different surface areas of calcium montmorillonite determined by chloride exclusion measurements.
Anilinium Montmorillonites and the Formation of Ammonium/Amine Associations
Authors: Heller Lisa , Yariv S. 
Published: November 2013

AbstractThe IR spectra, X‐ray patterns and DTA curves of various aryl ammonium montmorillonites, are characterized. Depending upon the particular amine, the aryl ammonium ions react with excess base by (1) showing a proton equally between two amine molecules through a water bridge, (2) by retaining the proton identified with one molecule, or (3) by polymerization liberating protons. It is inferred that interlayer alkyl ammonium ions also show protons with excess amine through water bridges but the stability of the aryl and alkyl compounds differs greatly.
Non‐Exchangeable Ammonium Ions in Some Clays and Shales of Israel
Authors: Yaalon D.H. , Feigin A. 
Published: November 2013

AbstractInorganic lattice‐bound ammonium was determined in a representative assemblage of Israeli shales and clayey rocks. Clays in which illite was the dominant mineral contained over 300 ppmN or >2 meq NH4/100g clay. This represents some 75% of the total nitrogen of the samples. Montmorillonite rich clays in marine sediments with small amounts of illite contained 0.5–1.5 meq NH4/100g clay or about 60% of the total N in the inorganic form. Montmorillonitic red beds held only small amounts of inorganically bound ammonium and kaolinitic clays, both of residual weathering and of hydrothermal origin, contained practically none.
Molecular Structure of the New Copper Complexes. VIII. Infrared Spectroscopic Evidence of the Cu2+ Ion Interaction with Aniline Derivates (Chloro and Nitroanilines)
Authors: Crâciunescu D. , Oancea D. 
Published: November 2013

AbstractCopper (II) complexes of the types [CuCl2L2] and [CuCl4]H2·2L, where L = m and p nitroaniline, (o, m and p) chloroaniline were prepared in solid crystalline form and their IR spectra was recorded at 25°C as Nujoll mulls and KBr pellets. A close linear relationship between the strength of the Cu ‐ N bond, deduced from the perturbations of the NH2 stretching frequencies, and the basic strength of the amino group were observed.
Magnetic Nonequivalence in Some 4 Substituted 2‐Phenyl‐2‐Thiazolin‐5‐Ones
Authors: Glotter E. , Bachi M. D. 
Published: November 2013

AbstractThe NMR spectra of the thiazolinone derivatives IIa‐d and IIIb‐d have been studied. The isopropyl methyl groups in Ha are diastereotopic and possess different chemical shifts, whereas in the tautomeric hydroxythiazole form IVa these groups are enantiotopic and display only one doublet. The diastereotopic methylene groups in IIb and IIIb exhibit a double magnetic nonequivalence: the two CH2 groups have different chemical shifts, however the protons of one methylene are isochronous and show an A2 pattern, whereas the protons within the second methylene are nonequivalent and show an AB pattern. The nonequivalence of the methylene groups is due mainly to the intrinsic diastereomerism of the molecule and is only slightly influenced by temperature, while the nonequivalence of the protons within one of the methylenes is strongly affected by temperature and is related to the different degree of population of the various conformers. Compounds IIc, d as well as IIIc, d are diastereomers by external comparison and the methylene protons show a nonequivalence similar to that of IIb.
DL‐homoserinehydroxamic Acid, DL‐homo‐cystinedihydroxamic Acid, and Derivatives by Hydroxylaminolysis of γ‐Hydroxy‐ and γ‐Thio‐Lactones
Authors: Knobler Y. , Bittner S. , Frankel M. 
Published: November 2013

AbstractThe reaction of α‐amino‐, α‐carbamoylamino‐, α‐benzamido‐, and α‐benzyloxycarbonyl‐amino‐γ‐butyrolactone with hydroxylamine led to the formation of DL‐homoserinehydroxamic acid and α‐N‐acyl derivatives. α‐N‐Benzoyl‐DL‐homoserine‐N‐methyl‐hydroxamic acid and O‐benzylhydroxamic acid ester were prepared by reacting α‐benzamido‐γ‐butyrolactone with N‐methylhydroxylamine and with O‐benzylhydroxylamine, respectively. Hydroxyl‐aminolysis of DL‐homocysteinethiolactone and of N‐acyl‐DL‐homocysteinethiolactones gave homocystinedihydroxamic acid and N,N′‐disubstituted derivatives. Relative reactivities of O‐ and S‐lactones were compared.
Aminoacyloxy Oligostannoxanes
Authors: Frankel M. , Migdal S. , Gertner D. , Zilkha A. 
Published: November 2013

AbstractOligomeric stannoxanes having the general formulamagnified imagewere prepared by treating amino and N‐acylamino‐acids with polymeric dibutyltin oxide at molar ratios less than 1. Shorter oligomers were built up to higher oligomers by insertion of dibutyltin oxide units.
Pyrolytic Reaction of Carbohydrates. Part IX the Effect of Additives on the Thermal Behavior of Cellulose Samples of Different Crystallinity
Authors: Patai S. , Halpern Y. 
Published: November 2013

AbstractThe thermal decomposition of four different cellulose samples (untreated cellulose, powdered or ball‐milled Whatman 544 filter paper, and micro‐crystalline cellulose) was studied at 250°. In samples heated either alone or in the presence of NaHSO4, Na2SO4, Na3PO4, or NaCl for 2 or 4 hr, weight loss, total organic volatiles, levoglucosan, water, acids, average degree of polymerization, and crystallinity index were determined. The results obtained are tabulated and compared. Whereas pretreatment and crystallinity considerably affect the pyrolytic behavior of the different samples, the presence of additives tends to mask the observable differences.