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At least 1,171 records · Page 65Linked to original sources
PubMed2006

Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE review of genetic association studies.

Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to be associated with the risk of developing type 1 diabetes, yet published findings have been conflicting. In this study, the authors attempted to evaluate the evidence regarding the association. They searched all relevant reports from original papers published from 1997 to December 2005. Predefined criteria were used to identify 1) case-control association studies examining the FokI (11 studies), BsmI (13 studies), ApaI (9 studies), and TaqI (7 studies) polymorphisms and 2) a few family-transmission studies with analysis of these four polymorphisms. In random-effects modeling, the 95% confidence intervals of the summary odds ratios for all four polymorphisms included 1, indicating no effect. Except for FokI, no heterogeneity was found. The 95% confidence intervals of the transmission proportions all included 0.5, indicating no effect. Thus, the authors found no evidence for an association between VDR gene polymorphisms and type 1 diabetes risk in either case-control studies or family-transmission studies. In fact, a reanalysis of previously published data (McDermott et al., Diabetologia 1997;40:971-5) indicated no evidence of an association as reported.

Case-Control Studies↗
PubMed2006

Reliable prediction of Drosha processing sites improves microRNA gene prediction.

MOTIVATION: Mature microRNAs (miRNAs) are processed from long hairpin transcripts. Even though it is only the first of several steps, the initial Drosha processing defines the mature product and is characteristic for all miRNA genes. Methods that can separate between true and false processing sites are therefore essential to miRNA gene discovery. RESULTS: We present a classifier that predicts 5' Drosha processing sites in hairpins that are candidate miRNAs. The classifier, called Microprocessor SVM, correctly predicts the processing site for 50% of known human 5' miRNAs, and 90% of its predictions are within two nucleotides of the true site. Another classifier that is trained on the output from the Microprocessor SVM outperforms existing methods for prediction of unconserved miRNAs. Reanalysis of characteristics and supporting evidence for a set of newly annotated miRNAs shows that some miRNAs may be misannotated. This suggests that expressed hairpins should not be annotated as miRNAs until they are verified to be Drosha and Dicer substrates. AVAILABILITY: The classifiers are publicly available at https://demo1.interagon.com/miRNA/

Artificial Intelligence↗
PubMed2001

Respiratory health and air pollution: additive mixed model analyses.

We conduct a reanalysis of data from the Utah Valley respiratory health/air pollution study of Pope and co-workers (Pope et al., 1991) using additive mixed models. A relatively recent statistical development (e.g. Wang, 1998; Verbyla et al., 1999; Lin and Zhang, 1999), the methods allow for smooth functional relationships, subject-specific effects and time series error structure. All three of these are apparent in the Utah Valley data.

Journal Article↗
PubMed2004

CLN3L, a novel protein related to the Batten disease protein, is overexpressed in Cln3-/- mice and in Batten disease.

Batten disease is a severe autosomal recessive neurodegenerative disease which results from mutations in CLN3. Although the gene was cloned in 1995, the tissue distribution and subcellular localization of the CLN3 protein (CLN3P) remains inconclusive. We have demonstrated the presence of a novel 33 kDa protein in both normal human and wild-type mouse brain. This 33 kDa protein, which is overexpressed in brains of patients with Batten disease and in Cln3-/- mouse brain, binds to the antibody raised against the peptide sequence of CLN3P and results in aberrant CLN3P localization studies. We expressed a novel 33 kDa protein that is highly similar to CLN3P. We showed that the 33 kDa protein is identical to that recognized in Batten disease and Cln3-/- brain. These studies strongly suggest the presence of an alternative CLN3-like (CLN3L) product in Batten disease. Previous studies of CLN3P tissue distribution and intracellular localization will require extensive reanalysis in order to determine the true expression of CLN3P.

Amino Acid Sequence↗
PubMed1992

Storage phosphor imaging technique for detection and quantitation of DNA adducts measured by the 32P-postlabeling assay.

The 32P-postlabeling method has found wide application as a sensitive technique for detecting the presence of a broad range of bulky aromatic compounds covalently bound to DNA. In this method, the modified DNA is enzymatically degraded to 3'-mononucleotides and labeled with [32P]-phosphate at the 5'-position using [gamma-32P]ATP and T4 polynucleotide kinase. The 32P-labeled DNA digest is then chromatographed in two dimensions on polyethyleneimine - cellulose thin-layer plates. Screen-enhanced autoradiography is used to locate the presence of the radiolabeled adducts on the chromatogram, and the radioactive areas are generally excised and quantitated by liquid scintillation spectrometry. However, on a chromatogram with multiple adducts, it can be difficult to quantitative partially resolved adducts and evaluated background radioactivity levels. We have evaluated the use of storage phosphor imaging techniques to quantitate and map the radioactivity on chromatograms generated by the 32P-postlabeling method. The results showed that storage phosphor imaging was approximately 10 times more sensitive than screen-enhanced autoradiography at -80 degrees C for the detection of 32P, exhibits a greater linear range of response, has a resolution that compares favorably to film and has a lower background than does liquid scintillation spectrometry. Further, the generation of a digitized record of the distribution and intensity of radioactivity allows for computer-assisted assessment of adduct profiles and can facilitate quantitation of individual adducts and radioactive zones comprised of multiple overlapping adducts in complex chromatograms. Additionally, the permanent record created by the imaging technology permits facile retrospective analysis of samples, whereas with autoradiography and liquid scintillation spectrometry reanalysis of a replicate sample is required.

Animals↗
PubMed1995

P53 polymorphisms and haplotypes in lung cancer.

An association between the BstU I 1-1 (Pro-Pro) genotype of the p53 codon 72 polymorphism and lung cancer has previously been reported by Kawajiri et al. A reanalysis of the data by Kawajiri et al. revealed no significant difference between patients and controls with respect to allele frequencies, and the increased frequency of BstU I 1-1 homozygotes was mostly ascribable to a deviation from the Hardy-Weinberg equilibrium. In an attempt to replicate the results by Kawajiri et al. we have studied three p53 polymorphisms (BstU I and Msp I RFLPs in exon 4 and intron 6 respectively and a 16 bp duplication in intron 3) and their haplotypes in Swedish lung cancer patients and controls. The results concerning the codon 72 polymorphism were largely negative. Thus there was no significant association between lung cancer and the BstU I 1-1 type, and only a marginal difference (P = 0.044) with respect to the BstU I allele frequency when lung cancer patients were compared with patients with chronic obstructive pulmonary disease (COPD). However, when the analysis was based on haplotype frequencies larger differences appeared and it was found that only BstU I 1 (pro) alleles linked to 16 bp 1 alleles were associated with lung cancer. Pro alleles linked to the 16 bp duplication appeared instead to confer some protection against cancer. Thus the codon 72 alleles need not be functionally involved in lung cancer, but may rather be markers in linkage disequilibrium with other cancer susceptibility sites on p53.

Alleles↗
PubMed2006

Brain structure predicts the learning of foreign speech sounds.

Previous work has shown a relationship between parietal lobe anatomy and nonnative speech sound learning. We scanned a new group of phonetic learners using structural magnetic resonance imaging and diffusion tensor imaging. Voxel-based morphometry indicated higher white matter (WM) density in left Heschl's gyrus (HG) in faster compared with slower learners, and manual segmentation of this structure confirmed that the WM volume of left HG is larger in the former compared with the latter group. This finding was replicated in a reanalysis of the original groups tested in Golestani and others (2002, Anatomical correlates of learning novel speech sounds. Neuron 35:997-1010). We also found that faster learners have a greater asymmetry (left > right) in parietal lobe volumes than slower learners and that the right insula and HG are more superiorly located in slower compared with faster learners. These results suggest that left auditory cortex WM anatomy, which likely reflects auditory processing efficiency, partly predicts individual differences in an aspect of language learning that relies on rapid temporal processing. It also appears that a global displacement of components of a right hemispheric language network, possibly reflecting individual differences in the functional anatomy and lateralization of language processing, is predictive of speech sound learning.

Adolescent↗
PubMed1991

When plagiarism becomes research.

There are three possible levels of analysis in clinical research. Primary analysis deals with the original analysis of research study data. Secondary analysis is a reanalysis of the original data, either to address the original question through better techniques or to address a new question using old data. Meta-analysis is a statistical analysis of many studies done to summarize a body of literature. Meta-analysis is particularly helpful in an area in which original research studies have produced conflicting results because it enables analysis of the impact of study characteristics upon the end result. The family practitioner as a consumer of research needs to become familiar with the technique of meta-analysis because it is appearing with increasing frequency in the medical literature. Still somewhat controversial, meta-analysis requires a rigorous approach to ensure its validity: this editorial is written to assist the family practitioner in an understanding of the meta-analytic technique and point out important features that need to appear in any published meta-analysis.

Bias↗
PubMed1986

Nonhomologous pairing in mice heterozygous for a t haplotype can produce recombinant chromosomes with duplications and deletions.

We have investigated the structure and properties of a chromosomal product recovered from a rare recombination event between a t haplotype and a wild-type form of mouse chromosome 17. Our embryological and molecular studies indicate that this chromosome (twLub2) is characterized by both a deletion and duplication of adjacent genetic material. The deletion appears to be responsible for a dominant lethal maternal effect and a recessive embryonic lethality. The duplication provides an explanation for the twLub2 suppression of the dominant T locus phenotype. A reanalysis of previously described results with another chromosome 17 variant called TtOrl indicates a structure for this chromosome that is reciprocal to that observed for twLub2. We have postulated the existence of an inversion over the proximal portion of all complete t haplotypes in order to explain the generation of the partial t haplotypes twLub2 and TtOrl. This proximal inversion and the previously described distal inversion are sufficient to account for all of the recombination properties that are characteristic of complete t haplotypes. The structures determined for twLub2 and TtOrl indicate that rare recombination can occur between nonequivalent genomic sequences within the inverted proximal t region when wild-type and t chromosomes are paired in a linear, nonhomologous configuration.

Alleles↗
PubMed1986

A rehabilitation of the genetic map of the 84B-D region in Drosophila melanogaster.

A reanalysis of the 84B3 to 84D3,5 region of the polytene chromosomes of Drosophila melanogaster has led to the identification and localization of 16 genes. These genes include 11 vital loci, four genes exhibiting nonlethal visible mutant phenotypes and one gene encoding a nonessential enzyme. The identity of the gene products of two of the vital genes has been determined to be alpha-tubulin and glucose dehydrogenase (Gld). Three newly identified genes, sticking (stk), half out (hat) and trapped (ted), as well as Gld are required for eclosion. Among the nonessential genes are roughened eye (roe) and ruffed eye (rue), which affect eye texture. The roe phenotype is greatly enhanced by deletions that simultaneously remove roe and an unidentified locus in 84E. Mutations in another nonessential gene, rotund (rn), are characterized by pattern deletions of most adult appendages.

Animals↗
PubMed1975

Marginal overdominance in Drosophila.

A reanalysis of Drosophila viability data was undertaken to determine the role of genotype-environment interactions in the maintenance of polymorphism. Between-replicate variances of viabilities in chromosomal homozygotes and heterozygotes with the same mean fitnesses were compared, with the expectation that if the heterozygote variance were on the average greater, conditional overdominance would be prevalent; if it were less, partial dominance would be prevalent; and if it were the same, marginal overdominance of the type considered by Wallace (1968) would be the prevalent type of variation. In fact, heterozygote variance was slightly less. The work of Dempster (1955) and of Gillespie and Langley (1974) is cited to show that this situation can still lead to balanced polymorphisms. Their general model for genetic variation in populations, consistent with the viability data, is reinforced.

Animals↗
PubMed1977

Centromeric effect on the degree of nonrandom disjunction in the female Drosophila melanogaster.

From crosses of females possessing a heteromorphic X-chromosome bivalent, FR1/+, the shorter crossover products were recovered on the average more frequently than the longer reciprocals as predicted by Novitski's (1951) hypothesis of nonrandom disjunction (NRD). The present study stemmed from an unexpected result of these crosses. Evidence for a centromeric effect on NRD was obtained, suggested by a negative correlation between the degree of NRD, c, and the distance between the region of exchange and the centromere as inferred from SET's (single exchange tetrads). Studies on sex chromosome systems other than FR1 confirmed these results. An analogous centromeric effect on preferential segregation had been clearly demonstrated in maize (Kikudome 1958, 1959; Rhoades and Dempsey 1966). However, prior to the present investigation, no such effect of the centromere on NRD in Drosophila had been described, although reanalysis of part of the data of Novitski (1951) and Novitski and Sandler (1956) suggests some evidence of a seriation of increasing c values extending from the most distal region of the chromosome toward the centromere. A suggestion that the effect in Drosophila may be related in some way to the time required for chiasma terminalization, i.e., those terminalizing earlier (distally located crossovers) permitting more random disjunction of the chromatids from the asymmetric dyad and those terminalizing later, progressively less random, is considered and rejected since in general the expected pattern of c values for the various double exchange tetrads (DET's) is inconsistent with that prediction and provides evidence suggesting the possibility of reversals, in part, of c values obtained for SET's.

Animals↗
PubMed1977

The detection of sympatric sibling species using genetic correlation analysis. I. Two loci, two gamodemes.

Four models are presented describing zygotic frequencies at two loci for one or two sympatric but genetically differentiated populations of "gamodemes." Linkage disequilibrium within gamodemes is allowed in two of the models. Maximum likelihood criteria are used to fit the models to the observed numbers of zygotes in a sample. A fitting-testing sequence for choosing a best model is described and the power of the test is analyzed. The statistical characteristics of the genetic parameter estimates were examined by simulation studies. In general, estimates were reliable when allele frequency differences between gamodemes were greater than 0.30 at both loci. This method may be used to study the population structure of samples with fewer heterozygotes than expected for Hardy-Weinberg populations, including the detection and genetic description of sibling species having overlapping ranges.--An example is given for Drosophila longicornis and D. propachuca, two sibling species within the mulleri complex of the repleta group which have been studied in detail using more conventional techniques. The reanalysis using the approach derived in this paper confirmed the reproductive isolation of these two species, and hinted at the possibility of further subdivision within D. propachuca.

Alleles↗
PubMed1998

Age variance of left ventricular diameters in dogs with cardiac disease.

Ventricular size increases during growth, but often due to cardiac disease. This study aims to describe left ventricular dimension interrelations using a representation that is applicable to patients with cardiac disease, and subsequently to statistically study possible age and gender influences in a large population. In retrospect we analyzed echocardiographically obtained diameters of the left ventricle in 442 dogs of various breeds with congenital or acquired heart disease. Also, we compared our findings with published data on humans and other animals. Multivariate regression analysis was applied to assess possible influences of age and gender. A high correlation was found for end-systolic diameter (ESD) versus end-diastolic diameter (EDD): ESD (cm) = -1.01 cm + 0.93 x EDD (cm) with r = 0.94, p < .00001. Next, these patients were categorized into three age groups (divisions at 3 and 7 years). We detected a slight age dependent effect: the regression coefficients for the younger group differed from the two older groups. No significant gender-related influence was detected. The observation of a high correlation for the ESD versus EDD relationship could be confirmed by reanalysis of published data on normal individuals and human patients. The newly described relationship between ESD and EDD applies in particular to cardiac patients. This is a relevant finding, because clinically important indices of ventricular performance generally depend on ESD, EDD or both. Thus, ESD versus EDD offers a convenient framework for studies on cardiac volume regulation and performance in the cardiopathological spectrum, while permitting incorporation of modulating effects related to age.

Age Factors↗
PubMed1991

The influence of dietary restriction, germ-free status, and aging on adrenal catecholamines in Lobund-Wistar rats.

Adrenal catecholamines (CA) were measured in 6-, 18-, and 30-mo Lobund-Wistar rats (LWR) maintained under germ-free or conventional conditions and fed either ad libitum or a restricted (70% of adult ad libitum) diet. Levels of dopamine (DA), norepinephrine (NE), epinephrine (E), and dihydroxymandelic acid (DHMA) were determined by HPLC-EC. Compared with values from 6- and 18-mo rats, mean adrenal weight, DA and NE content and concentration, and E content were increased in the 30-mo rats; E concentration was not. The ratio of E:NE declined in the 30-mo group. Germ-free status and dietary restriction had little effect in modulating these age-related changes. Reanalysis of adrenal weights of 30-mo rats revealed two clear subgroups, hyperplastic and non-hyperplastic; the data from hyperplastic adrenals revealed an exaggerated form of the "aged" CA profile, whereas data from the nonhyperplastic adrenals more closely resembled that of younger rats. Thus, aging in LWR is associated with adrenal hyperplasia and a tendency toward elevated adrenomedullary stores of DA and NE, while E stores are maintained near levels found in young rats.

Adrenal Glands↗
PubMed2003

Default biosynthesis pathway for blood group-related glycolipids in human small intestine as defined by structural identification of linear and branched glycosylceramides in a group O Le(a-b-) nonsecretor.

Glycoconjugates of the GI tract are important for microbial interactions. The expression of histo-blood group glycosyltransferases governs both the expression of blood group determinants and in part the structure and size of the glycoconjugates. Using neutral glycolipids isolated from the small intestine of a rare blood group O Le(a-b-) ABH secretor-negative (nonsecretor) individual we were able to map the "default" pathway of the individual lacking ABO, Lewis, and secretor glycosyltransferases. Structures were deduced with combined analysis of mass spectrometry (MALDI-TOF and ESI-MS/MS), and 1H NMR (500 and 600 MHz). All structures present at a level >5% were structurally resolved and included two extended structures: Galbeta4(Fucalpha3)GlcNAcbeta3(Galbeta4[Fucalpha3]GlcNAcbeta6)Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer and Galbeta3GlcNAcbeta3(Galbeta4[Fucalpha3]GlcNAcbeta6)Galbeta3GlcNAcbeta3Galbeta4Glcbeta1Cer. The first, a novel component, is based on a type 2 chain and bears the Lex glycotopes on both its branches. The second, a major component, is based on a type 1 chain, which bears a 3-linked type 1 precursor (Lec) glycotope and a 6-linked Lex glycotope on its branches. This latter structure is identical to that previously isolated from plasma and characterized by MS and GC-MS but not by NMR. Structural resolution of these structures was supported by reanalysis of the blood group H-active decaosylceramides previously isolated from rat small intestine. Other minor linear monofucosylated penta-, hepta-, and difucosylated octaosylceramides, some bearing blood group determinants, were also identified. The cumulative data were used to define a default biosynthesis pathway where it can be seen that carbohydrate chain extension, in the absence of blood group glycosyltransferases, is controlled and regulated by non-blood group fucosylation and branching with type 2 Galbeta4GlcNAc branches.

Animals↗
PubMed2004

Enhancing linkage analysis of complex disorders: an evaluation of high-density genotyping.

To explore the potential value of recently developed high-density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK multiple sclerosis linkage genome screen, using Applied Biosystems high-density microsatellite linkage mapping set, the Illumina BeadArray linkage mapping panel (version 3) and the Affymetrix GeneChip Human Mapping 10K array. We found that genotyping success, information extraction and genotyping accuracy were improved with all systems. These improvements were particularly marked with the SNP-based methods (Illumina and Affymetrix), with little difference between these. The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power.

Chromosome Mapping↗
PubMed2004

Hormones and breast cancer.

The incidence of breast cancer in women varies with age, mammary gland mass and exposure to endogenous and exogenous hormones. Age is the single most important factor and if, as projected, 32% of women will be aged >60 years by 2050, world breast cancer incidence will exceed the current 10(6) per year. Hormonal influences that affect growth of the mammary gland increase the risk of breast cancer; for example earlier menarche and later menopause. Childbearing protects against later development of breast cancer, and breastfeeding further decreases the risk. The breast cancer risk declines more with increasing total duration of breastfeeding. Exposure to hormonal contraceptives has been evaluated in a combined reanalysis of data from 51 epidemiological studies. There is a small transient increase in the relative risk of breast cancer among users of oral contraceptives but, since use typically occurs at young ages when breast cancer is relatively rare, such an increase would have little effect on overall incidence rates. In contrast, exposure to menopause hormone treatment occurs when the baseline risk of breast cancer is higher, and epidemiological studies and randomized controlled trials consistently find an increase in breast cancer risk with exposure to combined estrogen and progestogen. Women with a family history of breast cancer in first degree relatives have an increased risk of breast cancer but there is no evidence to suggest that this differs according to a woman's use of oral contraceptives or menopause hormone treatment. Selective estrogen receptor modulators are useful in the treatment and/or prevention of breast cancer depending on the specific agonist or antagonist effects on estrogen target tissues.

Age Factors↗