3,697 research outputs found
Mapping a gene for rheumatoid arthritis on chromosome 18q21
No full textAlthough single chi-square analysis of the North American Rheumatoid Arthritis Consortium (NARAC) data identifies many single-nucleotide polymorphisms (SNPs) with p-values less than 0.05, none remain significant after Bonferroni correction. In contrast, CHROMSCAN evades heavy Bonferroni correction and auto-correlation between SNPs by using composite likelihood to model association across all markers in a region and permutation to assess significance. Analysis by CHROMSCAN identifies a 36-kb interval that includes the most significant SNP (msSNP) observed in a 10-Mb target suggested by linkage. Unexpectedly, stratification by gender and age of onset shows that association evidence comes almost entirely from females with age of onset less than 40. Combining evidence from a meta-analysis of linkage studies and three subsets of the NARAC data provides significant evidence for a determinant of rheumatoid arthritis in a 36-kb interval and illustrates the principle that estimates of location and its information are more powerful than estimates of p-values alone
LDB2000: sequence-based integrated maps of the human genome
No full textMOTIVATION:
Integrated maps are useful for gene mapping and establishing the relationship between recombination and sequence. In this paper we describe algorithms and their implementation for constructing sequence-based integrated maps of the human chromosomes, which are presented in LDB2000, a web based resource. Gene mapping efforts are now focussing on linkage disequilibrium mapping and extension of the integrated map to represent the extent of linkage disequilibrium in different genomic regions would further increase the utility of these maps.
RESULTS:
Sequence-based integrated maps have been completed for chromosomes 21 and 22. These maps provide locations for genes and polymorphic markers in sequence and on genetic linkage, radiation hybrid and cytogenetic scales. Single nucleotide polymorphisms associated with genes in the maps are also included and their sequence locations indicated. Related locus information, such as aliases and expression information, can be searched on the WWW site
Mapping oligogenes for atopy and asthma by meta-analysis
No full textMeta-analysis is presented for published studies on linkage or allelic association that have in common only reported significance levels. Reporting is biassed, and nonsignificance is seldom quantified. Therefore meta-analysis cannot identify oligogenes within a candidate region nor establish their significance, but it defines candidate regions well. Applied to a database on atopy and asthma, candidate regions are identified on chromosomes 6, 5, 16, 11, 12, 13, 14, 7, 20, and 10, in rank order from strongest to weakest evidence. On the other hand, there is little support for chromosomes 9, 8, 18, 1, and 15 in the same rank order. The evidence from 156 publications is reviewed for each region. With reasonable type I and II errors several thousand affected sib pairs would be required to detect a locus accounting for 1/10 of the genetic effect on asthma. Identification of regions by a genome scan for linkage and allelic association requires international collaborative studies to reach the necessary sample size, using lod-based methods that specify a weakly parametric alternative hypothesis and can be combined over studies that differ in ascertainment, phenotypes, and markers. This has become the central problem in complex inheritance. <br/
A map of the human genome in linkage disequilibrium units
No full textTwo genetic maps with additive distances contribute information about recombination patterns, recombinogenic sequences, and discovery of genes affecting a particular phenotype. Recombination is measured in morgans (w) over a single generation in a linkage map but may cover thousands of generations in a linkage disequilibrium (LD) map measured in LD units (LDU). We used a subset of single nucleotide polymorphisms from the HapMap Project to create a genome-wide map in LDU. Recombination accounts for 96.8% of the LDU variance in chromosome arms and 92.4% in their deciles. However, deeper analysis shows that LDU/w, an estimate of the effective bottleneck time (t), is significantly variable among chromosome arms because (i) the linkage map is approximated from the Haldane function, then adjusted toward the Kosambi function that is more accurate but still exaggerates w for all chromosomes, especially shorter ones; (ii) the nonpseudoautosomal region of the X chromosome is subject to hemizygous selection; and (iii) at resolution less than ?40,000 markers per w, there are indeterminacies (holes) in the LD map reflecting intervals of very high recombination. Selection and stochastic variation in small regions must have effects, which remain to be investigated by comparisons among populations. These considerations suggest an optimal strategy to eliminate holes quickly, greatly enhance the resolution of sex-specific linkage maps, and maximize the gain in association mapping by using LD maps
Swedish Cops : From Sjöwall & Wahlöö to Stieg Larsson
No full textMichael Tapper considers Swedish culture and ideas from the period 1965 to 2012 as expressed in detective fiction and film in the tradition of Maj Sjöwall and Per Wahlöö. Believing the Swedish police narrative tradition to be part and parcel of the European history of ideas and culture, Tapper argues thaSwedish Copst, from being feared and despised, the police emerged as heroes and part of the modern social project of the welfare state after World War II.Establishing themselves artistically and commercially in the forefront of the genre, Sjöwall and Wahlöö constructed a model for using the police novel as an instrument for ideological criticism of the social democratic government and its welfare state project. With varying political affiliations, their model has been adapted by authors such as Leif G. W. Persson, Jan Guillou, Henning Mankell, Håkan Nesser, Anders Roslund and Börge Hellström, and Stieg Larsson, and in film series such as Beck and Wallander. The first book of its kind about Swedish crime fiction, Swedish Cops: From Sjöwall and Wahlöö to Stieg Larsson is just as thrilling as the novels and films it analyses
Haplotypic analysis of the matrix metalloproteinase-9 gene in relation to coronary artery disease
No full textSwedish Cops From Sjöwall & Wahlöö to Stieg Larsson
No full textMichael Tapper considers Swedish culture and ideas from the period 1965 to 2012 as expressed in detective fiction and film in the tradition of Maj Sjöwall and Per Wahlöö. Believing the Swedish police narrative tradition to be part and parcel of the European history of ideas and culture, Tapper argues thaSwedish Copst, from being feared and despised, the police emerged as heroes and part of the modern social project of the welfare state after World War II. Establishing themselves artistically and commercially in the forefront of the genre, Sjöwall and Wahlöö constructed a model for using the police novel as an instrument for ideological criticism of the social democratic government and its welfare state project. With varying political affiliations, their model has been adapted by authors such as Leif G. W. Persson, Jan Guillou, Henning Mankell, Håkan Nesser, Anders Roslund and Börge Hellström, and Stieg Larsson, and in film series such as Beck and Wallander. The first book of its kind about Swedish crime fiction, Swedish Cops: From Sjöwall and Wahlöö to Stieg Larsson is just as thrilling as the novels and films it analyses
A tournament of linkage tests in complex inheritance
No full textThe performance of some weakly parametric linkage tests in common use was compared on 200 replicates of oligogenic inheritance from Genetic Analysis Workshop 10. Each random sample for the quantitative trait was dichotomized at different thresholds and also selected through 2 affected sibs, generating 8 combinations of sample and variable. The variance component program SOLAR performed best with a continuous trait, even in selected samples, when the population mean was used. The sib-pair program SIBPAL2 was best in most other cases when the phenotype product, population mean, and empirical estimates of pair correlations were used. The BETA program that introduced phenotype products was slightly more powerful than maximum likelihood scores under the null hypothesis and approached but did not exceed SIBPAL2 under its optimal conditions. Type I errors generally exceeded expectations from a chi2 test, but were conservative with respect to bounds on lods. All methods can be improved by use of the population mean, empirical correlations, logistic representation for affection status, and correct lods for samples that favour the null hypothesis. It remains uncertain whether all information can be extracted by weakly parametric methods and whether correction for ascertainment bias demands a strongly parametric model. Performance on a standard set of simulated data is indispensable for recognising optimal methods
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