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Gravitational dynamos and the low-frequency geomagnetic secular variation.

ABSTRACT: Self-sustaining numerical dynamos are used to infer the sources of low-frequency secular variation of the geomagnetic field. Gravitational dynamo models powered by compositional convection in an electrically conducting, rotating fluid shell exhibit several regimes of magnetic field behavior with an increasing Rayleigh number of the convection, including nearly steady dipoles, chaotic nonreversing dipoles, and chaotic reversing dipoles. The time average dipole strength and dipolarity of the magnetic field decrease, whereas the dipole variability, average dipole tilt angle, and frequency of polarity reversals increase with Rayleigh number. Chaotic gravitational dynamos have large-amplitude dipole secular variation with maximum power at frequencies corresponding to a few cycles per million years on Earth. Their external magnetic field structure, dipole statistics, low-frequency power spectra, and polarity reversal frequency are comparable to the geomagnetic field. The magnetic variability is driven by the Lorentz force and is characterized by an inverse correlation between dynamo magnetic and kinetic energy fluctuations. A constant energy dissipation theory accounts for this inverse energy correlation, which is shown to produce conditions favorable for dipole drift, polarity reversals, and excursions.

SUBMITTER: Olson P

PROVIDER: S-EPMC2154401 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The functional spectrum of low-frequency coding variation.

Project description:BackgroundRare coding variants constitute an important class of human genetic variation, but are underrepresented in current databases that are based on small population samples. Recent studies show that variants altering amino acid sequence and protein function are enriched at low variant allele frequency, 2 to 5%, but because of insufficient sample size it is not clear if the same trend holds for rare variants below 1% allele frequency.ResultsThe 1000 Genomes Exon Pilot Project has collected deep-coverage exon-capture data in roughly 1,000 human genes, for nearly 700 samples. Although medical whole-exome projects are currently afoot, this is still the deepest reported sampling of a large number of human genes with next-generation technologies. According to the goals of the 1000 Genomes Project, we created effective informatics pipelines to process and analyze the data, and discovered 12,758 exonic SNPs, 70% of them novel, and 74% below 1% allele frequency in the seven population samples we examined. Our analysis confirms that coding variants below 1% allele frequency show increased population-specificity and are enriched for functional variants.ConclusionsThis study represents a large step toward detecting and interpreting low frequency coding variation, clearly lays out technical steps for effective analysis of DNA capture data, and articulates functional and population properties of this important class of genetic variation.

| S-EPMC3308047 | biostudies-literature

No large-effect low-frequency coding variation found for myocardial infarction.

Project description:Genome-wide association studies have identified variants, primarily common, that are associated with coronary artery disease or myocardial infarction (MI), but have not tested the majority of the low frequency and rare variation in the genome. We explored the hypothesis that previously untested low frequency (1-5% minor allele frequency) and rare (<1% minor allele frequency) coding variants are associated with MI. We genotyped 2906 MI cases and 6738 non-MI controls from Norway using the Illumina HumanExome Beadchip, allowing for direct genotyping of 85 972 polymorphic coding variants as well as 48 known GWAS SNPs. We followed-up 34 coding variants in an additional 2350 MI cases and 2318 controls from Norway. We evaluated exome array coverage in a subset of these samples using whole exome sequencing (N = 151). The exome array provided successful genotyping for an estimated 72.5% of Norwegian loss-of-function or missense variants with frequency >1% and 66.2% of variants <1% frequency observed more than once. Despite 80% power in the two-stage study (N = 14 312) to detect association with low-frequency variants with high effect sizes [odds ratio (OR) >1.86 and >1.36 for 1 and 5% frequency, respectively], we did not identify any novel genes or single variants that reached significance. This suggests that low-frequency coding variants with large effect sizes (OR >2) may not exist for MI. Larger sample sizes may identify coding variants with more moderate effects.

| S-EPMC4119412 | biostudies-literature

Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk.

Project description:Multiple sclerosis is a complex neurological disease, with ?20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFN? biology, and NF?B signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.

| S-EPMC6269166 | biostudies-literature

Gravitational Waves from Gravitational Collapse.

Project description:Gravitational-wave emission from stellar collapse has been studied for nearly four decades. Current state-of-the-art numerical investigations of collapse include those that use progenitors with more realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non-axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with ground-based and space-based interferometric observatories. This review covers the entire range of stellar collapse sources of gravitational waves: from the accretion-induced collapse of a white dwarf through the collapse down to neutron stars or black holes of massive stars to the collapse of supermassive stars. ELECTRONIC SUPPLEMENTARY MATERIAL:Supplementary material is available for this article at 10.12942/lrr-2011-1.

| S-EPMC5255218 | biostudies-literature

Gravitational Waves from Gravitational Collapse.

Project description:Gravitational wave emission from stellar collapse has been studied for more than three decades. Current state-of-the-art numerical investigations of collapse include those that use progenitors with more realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non-axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with ground-based and space-based interferometric observatories. This review covers the entire range of stellar collapse sources of gravitational waves: from the accretion induced collapse of a white dwarf through the collapse down to neutron stars or black holes of massive stars to the collapse of supermassive stars.Electronic supplementary materialSupplementary material is available for this article at 10.12942/lrr-2003-2.

| S-EPMC5253977 | biostudies-literature

Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration.

Project description:OBJECTIVE:To investigate the influence of common and low-frequency genetic variants on the risk of ischemic stroke (all IS) and etiologic stroke subtypes. METHODS:We meta-analyzed 12 individual genome-wide association studies comprising 10,307 cases and 19,326 controls imputed to the 1000 Genomes (1 KG) phase I reference panel. We selected variants showing the highest degree of association (p < 1E-5) in the discovery phase for replication in Caucasian (13,435 cases and 29,269 controls) and South Asian (2,385 cases and 5,193 controls) samples followed by a transethnic meta-analysis. We further investigated the p value distribution for different bins of allele frequencies for all IS and stroke subtypes. RESULTS:We showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE). We further refined the association peaks for ABO and PITX2. Analyzing different allele frequency bins, we showed significant enrichment in low-frequency variants (allele frequency <5%) for both LVD and small vessel disease, and an enrichment of higher frequency variants (allele frequency 10% and 30%) for CE (all p < 1E-5). CONCLUSIONS:Our findings suggest that the missing heritability in IS subtypes can in part be attributed to low-frequency and rare variants. Larger sample sizes are needed to identify the variants associated with all IS and stroke subtypes.

| S-EPMC4818561 | biostudies-literature

Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration.

Project description: Not available

| S-EPMC5994705 | biostudies-literature

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

Project description:Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10-6), and rs7700147, an intergenic variant (P=2.93 × 10-5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

| S-EPMC5828108 | biostudies-literature

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume.

Project description:Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV?+?HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5?cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.

| S-EPMC6341110 | biostudies-literature

Single molecule molecular inversion probes for targeted, high-accuracy detection of low-frequency variation.

Project description:The detection and quantification of genetic heterogeneity in populations of cells is fundamentally important to diverse fields, ranging from microbial evolution to human cancer genetics. However, despite the cost and throughput advances associated with massively parallel sequencing, it remains challenging to reliably detect mutations that are present at a low relative abundance in a given DNA sample. Here we describe smMIP, an assay that combines single molecule tagging with multiplex targeted capture to enable practical and highly sensitive detection of low-frequency or subclonal variation. To demonstrate the potential of the method, we simultaneously resequenced 33 clinically informative cancer genes in eight cell line and 45 clinical cancer samples. Single molecule tagging facilitated extremely accurate consensus calling, with an estimated per-base error rate of 8.4 × 10(-6) in cell lines and 2.6 × 10(-5) in clinical specimens. False-positive mutations in the single molecule consensus base-calls exhibited patterns predominantly consistent with DNA damage, including 8-oxo-guanine and spontaneous deamination of cytosine. Based on mixing experiments with cell line samples, sensitivity for mutations above 1% frequency was 83% with no false positives. At clinically informative sites, we identified seven low-frequency point mutations (0.2%-4.7%), including BRAF p.V600E (melanoma, 0.2% alternate allele frequency), KRAS p.G12V (lung, 0.6%), JAK2 p.V617F (melanoma, colon, two lung, 0.3%-1.4%), and NRAS p.Q61R (colon, 4.7%). We anticipate that smMIP will be broadly adoptable as a practical and effective method for accurately detecting low-frequency mutations in both research and clinical settings.

| S-EPMC3638140 | biostudies-literature

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