bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ranks of Genuine Associations in Whole-Genome Scans
Authors: Zaykin Dmitri V , Zhivotovsky Lev A 
Published: July 2005

AbstractWith the recent advances in high-throughput genotyping techniques, it is now possible to perform whole-genome association studies to fine map causal polymorphisms underlying important traits that influence susceptibility to human diseases and efficacy of drugs. Once a genome scan is completed the results can be sorted by the association statistic value. What is the probability that true positives will be encountered among the first most associated markers? When a particular polymorphism is found associated with the trait, there is a chance that it represents either a “true” or a “false” association (TA vs. FA). Setting appropriate significance thresholds has been considered to provide assurance of sufficient odds that the associations found to be significant are genuine. However, the problem with genome scans involving thousands of markers is that the statistic values of FAs can reach quite extreme magnitudes. In such situations, the distributions corresponding to TAs and the most extreme FAs become comparable and significance thresholds tend to penalize TAs and FAs in a similar fashion. When sorting between true and false associations, the “typical” place (i.e., rank) of TAs among the most significant outcomes becomes important, ordered by the association statistic value. The distribution of ranks that we study here allows calculation of several useful quantities. In particular, it gives the number of most significant markers needed for a follow-up study to guarantee that a true association is included with certain probability. This can be calculated conditionally on having applied a multiple-testing correction. Effects of multilocus (e.g., haplotype association) tests and impact of linkage disequilibrium on the distribution of ranks associated with TAs are evaluated and can be taken into account.
The RuvAB Branch Migration Translocase and RecU Holliday Junction Resolvase Are Required for Double-Stranded DNA Break Repair in Bacillus subtilis
Authors: Sanchez Humberto , Kidane Dawit , Reed Patricia , Curtis Fiona A , Cozar M Castillo , Graumann Peter L , Sharples Gary J , Alonso Juan C 
Published: July 2005

Abstract
In models of Escherichia coli recombination and DNA repair, the RuvABC complex directs the branch migration and resolution of Holliday junction DNA. To probe the validity of the E. coli paradigm, we examined the impact of mutations in ΔruvAB and ΔrecU (a ruvC functional analog) on DNA repair. Under standard transformation conditions we failed to construct ΔruvAB ΔrecG, ΔrecU ΔruvAB, ΔrecU ΔrecG, or ΔrecU ΔrecJ strains. However, ΔruvAB could be combined with addAB (recBCD), recF, recH, ΔrecS, ΔrecQ, and ΔrecJ mutations. The ΔruvAB and ΔrecU mutations rendered cells extremely sensitive to DNA-damaging agents, although less sensitive than a ΔrecA strain. When damaged cells were analyzed, we found that RecU was recruited to defined double-stranded DNA breaks (DSBs) and colocalized with RecN. RecU localized to these centers at a later time point during DSB repair, and formation was dependent on RuvAB. In addition, expression of RecU in an E. coli ruvC mutant restored full resistance to UV light only when the ruvAB genes were present. The results demonstrate that, as with E. coli RuvABC, RuvAB targets RecU to recombination intermediates and that all three proteins are required for repair of DSBs arising from lesions in chromosomal DNA.
Ultraviolet Radiation, Vitamin D and Risk of Prostate Cancer and Other Diseases
Authors: Moon Samuel J. , Fryer Anthony A. , Strange Richard C. 
Published: July 2005

ABSTRACTMost common diseases appear to result from complex, poorly understood interactions between genetic and environmental factors. Relatively few factors have been unequivocally linked with disease risk or outcome. Evidence from various studies using different experimental approaches has been interpreted as showing that, apart from its harmful effects on the pathogenesis of the common skin cancers, ultraviolet radiation (UVR) may exert a beneficial effect on development of various internal cancers and other pathologies. This concept is supported by parallel studies showing that hypovitaminosis D is linked with increased risk of various diseases including insulin resistance and multiple sclerosis. These findings suggest that, first, host factors such as skin pigmentation that affect UVR‐induced synthesis of vitamin D and, second, polymorphism in genes that mediate the effectiveness of vitamin D action are susceptibility candidates for a variety of diseases. Collectively, these data suggest the hypothesis that, via effects on vitamin D synthesis, UVR exposure has beneficial effects on susceptibility and outcome to a variety of complex diseases. We describe evidence from studies in various diseases, but mainly from prostate cancer patients, that supports this hypothesis, but we emphasize that, although supportive data are available, the concept is unproven. Indeed, other explanations are possible. However, given the potentially important public health implications of the hypothesis and the potential for the development of novel therapeutic modalities, we believe the concept is worthy of further investigation.
Genetic Variations in the Human Gelatinase A (Matrix Metalloproteinase‐2) Promoter Are Not Associated With Susceptibility to, and Severity of, Chronic Periodontitis
Authors: Holla Lydie Izakovicova , Fassmann Antonin , Vasku Anna , Goldbergova Monika , Beranek Michal , Znojil Vladimír , Vanek Jiri , Vacha Jiri 
Published: July 2005

Background: Gelatinase A (matrix metalloproteinase‐2 [MMP‐2]) has been shown to play an important role in the pathogenesis of several disorders, including periodontal diseases. In this study, we test the hypothesis that variations in this gene influence the development and severity of chronic periodontitis.Methods: Four promoter polymorphisms (‐1575G/A, ‐1306C/T, ‐790T/G, and ‐735C/T) were analyzed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) methods in 149 patients with mild to severe chronic periodontitis and 127 age‐matched controls in the Czech population.Results: No significant differences in distribution of the ‐1575G/A, ‐1306C/T, and ‐735C/T variants between periodontitis and control groups were detected in our study. However, a trend to decreased frequency of the ‐790 GG homozygotes was observed in patients with chronic periodontitis compared to healthy controls (P = 0.036, P corr >0.05). Haplotype analysis of four single nucleotide polymorphisms (SNP) in the MMP‐2 gene showed no significant association of any haplotype with chronic periodontitis.Conclusion: Our findings suggest that polymorphisms in the MMP‐2 gene promoter do not contribute significantly to the interindividual periodontitis susceptibility and/or severity in European Caucasians, and they are not regulatory variants in this disease. J Periodontol 2005;76:1056‐1060.
Resonance Frequency Analysis of One‐ Stage Dental Implant Stability During the Osseointegration Period
Authors: Ersanli S. , Karabuda C. , Beck F. , Leblebicioglu B. 
Published: July 2005

Background: Currently, there is no available clinical tool to evaluate the amount of osseointegration and stability around dental implants. It has been recently suggested that changes in the stiffness of an implant in bone during healing may be monitored by using resonance frequency analysis (RFA). The aim of this study was to determine whether RFA can be integrated into the routine clinical evaluation of initial healing of dental implants.Methods: Thirty‐one patients (18 female and 13 male; mean age of 51.7 years) were included into this study. A total of 122 implants and three different, but comparable, implant designs were evaluated by using RFA. The specific transducer for each implant system was used. ISQ (implant stability quotient) readings were obtained for each implant at the time of surgery, 3 and 6 weeks postoperatively, and at the time of loading (3 or 6 months following surgery). Data were analyzed for different healing times, various anatomical locations, implant length, and type. Average time in function was 12 months.Results: Two implants failed during healing. Implant stability was higher on the mandible compared to the maxilla for each implant system studied (Mann‐Whitney test, P <0.01). ISQ readings decreased significantly at 3 and 6 weeks post‐surgery compared to readings obtained at surgery (Wilcoxon matched pairs sign‐rank tests, P <0.01). A recovery to the initial ISQ levels was noted at the time of implant loading. The possible effects of different types and lengths of implants to ISQ readings were examined.Conclusions: Results of this study support the need for a clinical tool to evaluate dental implant stability prior to loading, especially for implants placed in the maxilla. It appears that implant stability is weakest at 3 to 6 weeks in one‐stage non‐loaded dental implants. ISQ readings can be used to determine different healing phases and the stability of dental implants. However, it is difficult to define a general standardized range of ISQ readings for successful implant integration for various implant systems. Thus, RFA values/ISQ levels should be calibrated for each implant system separately. Further studies are needed to compare the early changes seen in immediately loaded dental implants and to determine whether there is any time in which the total recovery in ISQ levels may occur. J Periodontol 2005;76:1066‐1071.
Periodontal Disease and the Incidence of Tooth Loss in Postmenopausal Women
Authors: Tezal Mine , Wactawski‐Wende Jean , Grossi Sara G. , Dmochowski Jacek , Genco Robert J. 
Published: July 2005

Background: The role of periodontal disease as a predictor of incident tooth loss in postmenopausal women has not been determined. The aim of this cohort study was to determine the extent of the association between baseline periodontal status and incident tooth loss in a population of postmenopausal women.Methods: The study population included 106 dentate white postmenopausal women who participated in a cross‐sectional study between 1989 and 1991 who were willing and eligible to have a repeat examination after 10 to 13 years. At baseline, full‐mouth assessment of periodontal status was performed clinically and radiographically. Assessment of tooth loss during follow‐ up was assessed clinically by a periodontist. Odds ratio (OR) and its 95% confidence interval (CI) for each periodontal variable was obtained from separate multiple logistic regression analyses adjusting for the effect of age, household income, smoking, hormone therapy, snack consumption, and number of decayed teeth.Results: Sixty‐one (57.5%) subjects lost at least one tooth during follow‐up. Mean tooth loss per person was 1.81 ± 2.77. After adjusting for confounders, each millimeter of alveolar bone loss at baseline increased the risk of tooth loss 3‐fold (OR = 3.26; 95% CI: 1.60 to 6.64). The risk of tooth loss also increased 2.5 times for each millimeter of clinical attachment loss (OR = 2.50; 95% CI: 1.24 to 5.07). Probing depth (OR = 2.53; 95% CI: 0.98 to 6.53), gingival bleeding (OR = 1.99; 95% CI: 0.21 to 18.94), calculus (OR = 2.05; 95% CI: 0.91 to 4.61), and plaque (OR = 0.70; 95% CI: 0.13 to 3.34) were not significantly associated with incident tooth loss.Conclusion: Periodontal disease, especially measured by alveolar bone loss, is a strong and independent predictor for incident tooth loss in postmenopausal women. J Periodontol 2005;76:1123‐1128.
The visualization of chromosomes
Authors: Schwartz Stuart 
Published: July 2005

Abstract
Chromosomes have been studied for over 100 years, and our methods of visualization have changed and improved over that time. These studies initially involved squash preparations of meiotic chromosomes and have evolved to the eloquent study of high‐resolution G‐banded chromosomes and most recently to the analysis of BAC arrays to detect small chromosomal changes. During this time, we have learned the true chromosome number in humans as well as a large variety of both aneuploidies and small deletion/duplication syndromes. In this overview, I will review the process underlying the increased visualization of chromosomes, the methodologies leading to the advances and the findings resulting from our increased resolution.
Preimplantation genetic diagnosis for chromosome abnormalities
Authors: Munné Santiago 
Published: July 2005

AbstractPreimplantation genetic diagnosis (PGD) is the earliest form of prenatal diagnosis and has been used in over 5000 infertile patient procedures to improve pregnancy outcome for in vitro fertilization (IVF). PGD has also been used to limit spontaneous abortions and chromosomally unbalanced or aneuploid offspring in patients of advanced maternal age or carriers of translocations or other chromosome abnormalities.
The histone code and epigenetic inheritance
Authors: Hoffman Andrew R. , Vu Thanh H. 
Published: July 2005

Abstract
The role of histones as active participants in gene regulation has only recently been appreciated. Previously, these proteins, which are assembled into nucleosomes, forming beads around which the DNA is wrapped, were considered to be relatively inert scaffolding for packaging the genetic material. However, the histones' amino‐terminal tails extend away from the central core, and are thus available for posttranslational, reversible acetylation, methylation, phosphorylation, ADP‐ribosylation, and ubiquitination. Amino acids in the histone cores may also be modified in a similar way. The enzymes responsible for these modifications are often specific for particular histones and for restricted amino acid residues. The array and combination of these specific attachments to the various histones have been postulated to constitute a code that may entail thousands of histone isoforms and that may make it possible to determine how these proteins will interact with their nearby DNA sequences. Histone modifications interact with DNA methylation to mark genes for silencing or transcription. In conjunction with DNA methylation, the histone code constitutes a heritable epigenetic signature that is faithfully replicated in daughter cells after cell division. The mechanism for transmitting the histone code to subsequent generations of cells remains to be fully elucidated. The study of the histone code is examined through the prism of the regulation of genomic imprinting. By reading the combinatorial and/or sequential histone modifications that constitute the histone code, it may be possible to predict which gene products will be transcribed and thus determine a cell's RNA repertoire and ultimately its proteome, just as reading the DNA code allows us to predict the encoded protein sequence.
Imprinting at the

GNAS

locus and endocrine disease
Authors: Weinstein Lee S. , Chen Min , Sakamoto Akio , Liu Jie 
Published: July 2005

Abstract

The ubiquitously expressed G protein α‐subunit G
s
α couples receptors to adenylyl cyclase and is required for the intracellular cyclic AMP response to hormones and other extracellular signals. G
s
α is one of several gene products of the
GNAS
locus at 20q13. G
s
α is imprinted in a tissue‐specific manner, being expressed primarily from the maternal allele in hormone‐target tissues such as renal proximal tubules, thyroid, ovary, and pituitary but biallelically expressed in most other tissues. Heterozygous G
s
α null mutations result in Albright hereditary osteodystrophy (AHO), which is characterized by obesity, short stature, and skeletal defects, and is likely the result of G
s
α haploinsufficiency in many tissues. Because of tissue‐specific G
s
α imprinting, patients who inherit their mutations maternally also develop resistance to multiple hormones (parathyroid hormone, thyrotropin) whose receptors activate G
s
α (a condition referred to as pseudohypoparathyroidism type 1A), while patients who inherit their mutations paternally only develop AHO. Pseudohypoparathyroidism type 1B (PHPIB), in which patients develop parathyroid hormone (and sometimes thyrotropin) resistance in the absence of AHO, is caused by
GNAS
imprinting defects in which a paternal epigenotype is present on both parental alleles. This presumably leads to G
s
α deficiency only in tissues where G
s
α is normally imprinted. Familial PHPIB is usually associated with a deletion of a region within the closely linked
STX16
gene that appears to be required for normal
GNAS
imprinting. Most likely, tissue‐specific G
s
α imprinting results from an indirect mechanism involving a closely linked differentially methylated region (DMR) whose imprinting is lost in PHPIB.
Initiation of
X
‐chromosome inactivation
Authors: Pereira Lygia V. , Stabellini Raquel 
Published: July 2005

Abstract

Dosage compensation is the process by which the amount of X‐linked gene products between individuals with one and two X chromosomes is equalized. In mammals, dosage compensation is achieved by the transcriptional silencing of one X chromosome in female cells. Inactivation is attained by the establishment of several sequential epigenetic modifications in the future inactive X triggered by expression of the
Xist
gene in cis, and including different histone modifications and methylation of CpG islands. These transformations occur during early embryonic development and require that the cell counts the X chromosomes and chooses one to be active per diploid genome, inactivating the others. Here, we will review what is currently known about the early events of X‐chromosome inactivation, and discuss the mechanisms by which a cell counts and chooses X chromosomes.
Parametric versus nonparametric and two‐point versus multipoint: controversies in gene mapping
Authors: Bailey‐Wilson Joan E. 
Published: July 2005

AbstractIn parametric or model‐based linkage analysis (often called LOD score linkage analysis), one assumes that models describing both the trait and marker loci are known without error. This means that one assumes that the allele frequencies, dominance relationships among the alleles, and relationships between genotypes and phenotypes are known without error at both the trait and marker loci. Nonparametric (or model‐free or weakly parametric) linkage methods make fewer assumptions about the trait model, although the assumption that the marker locus model(s) is known without error is still in force. These methods of analysis have different strengths and weaknesses that should be taken into account by the analyst when choosing how to analyze linkage data. Parametric linkage analysis is more powerful than nonparametric linkage methods if the genetic model for both trait and marker loci are correctly specified but for complex traits where such correct model specification is difficult, nonparametric methods may be more powerful. Both parametric and nonparametric analyses may be performed between a trait locus and a single marker locus (two‐point linkage) or between a trait locus and a map of multiple markers (multipoint linkage). Again, these methods have different strengths and weaknesses that should be understood before embarking upon their use. Multipoint methods give more power to detect linkage than two‐point methods as long as the marker order and intermarker distances are correctly specified and assumptions about the trait and marker models are correct, but failures of these assumptions may strongly decrease the power of multipoint methods.
Gene mapping and the transition from
STRPs
to
SNPs
Authors: Wijsman Ellen M. 
Published: July 2005

Abstract
Linkage analysis based on DNA markers is a major activity in human genetics. Time, cost, and inability to extract complete mapping information are important considerations. While multiallelic single tandem repeat polymorphisms (STRPs) have dominated for 15 years, single‐nucleotide polymorphisms (SNPs) are an alternative that may have some advantages. In considering a transition to SNPs, it is important to highlight the assumptions that may need to be reconsidered and additional analytical and computational challenges that are posed by the use of densely spaced diallelic markers. These are the issues that will affect the analysis and interpretation of results obtained with SNPs, and the modifications to the analytical techniques needed to make full use of this new type of data.
Algorithmic improvements in gene mapping
Authors: Abecasis Gonçalo R. , Zhao Yu 
Published: July 2005

Abstract
The analysis of human gene mapping data presents daunting computational challenges. Improvements in laboratory technology have motivated the development and refinement of increasingly sophisticated algorithms for the analysis of human pedigrees. We review and summarize some of the more important developments, and present a short history of the software packages that are now in widespread use in human gene mapping studies.
Choices in gene mapping: populations and family structures
Authors: Pollin Toni I. , O'Connell Jeffrey R. 
Published: July 2005

AbstractThere are many choices of population for gene mapping of complex diseases. Recent technological advances for genotyping single‐nucleotide polymorphisms have shifted our focus from family‐based gene mapping to large case‐control genome‐wide linkage disequilibrium mapping. However, genetic isolates remain an important resource for mapping complex diseases, as these populations have greater genetic and environmental homogeneity. In addition, emerging single‐molecule genotyping technologies will eliminate the current computational barriers of both linkage and association mapping in the rich extended pedigrees found in genetic isolates. These technologies will reaffirm the importance of genetic isolates for mapping susceptibility genes for complex diseases.
Polymorphic inversions, deletions, and duplications in gene mapping
Authors: Christian Susan L. 
Published: July 2005

Abstract
The underlying architecture of the human genome contains segmental duplications that predispose to the formation of inversions, deletions, and duplications. The effects of these chromosomal aberrations on gene mapping are multifold. Inversions may disrupt disease genes, while deletions and duplications produce genomic imbalances that may affect dosage of disease genes. These anomalies are not readily detected using standard linkage and association analyses. Current studies are ongoing to develop methods to detect gene dosage using high‐density SNP genotyping, while other studies are cataloging the copy number polymorphisms present in the genome. Determining whether these polymorphisms are benign or provide susceptibility to complex diseases will be an important question for future studies.
Allergy and asthma
Authors: Moffatt Miriam F. , Cookson William O.C. 
Published: July 2005

Abstract
Asthma and eczema (atopic dermatitis, AD) are the most common chronic diseases of childhood. These diseases are characterized by the production of high levels of immunoglobulin E in response to common allergens. Their development depends on both genetic and environmental factors. Genes and genetic loci that are associated with increased susceptibility to asthma and AD have been described. A surprising number of these are expressed in the mucosa and epidermis, suggesting that events at epithelial surfaces may be driving disease processes.
Complexity of cancer as a genetic disease
Authors: Vallenius Tea , Mäkelä Tomi P. 
Published: July 2005

Abstract
Our understanding of cancer as a genetic disease is increasingly growing using information from genome‐scale experimental approaches, and the focus is turning from analyzing single genes to analyzing signaling networks. Together with the first targeted therapy successes, this has resulted in an excitement and optimism in the field, while at the same time improved classification and diagnostics are identifying at increasing accuracy the patients who will benefit from a given therapy.