The role of fluids in lower-crustal earthquakes near continental rifts

The occurrence of earthquakes in the lower crust near continental rifts has long been puzzling, as the lower crust is generally thought to be too hot for brittle failure to occur. Such anomalous events have usually been explained in terms of the lower crust being cooler than normal. But if the lower crust is indeed cold enough to produce earthquakes, then the uppermost mantle beneath it should also be cold enough, and yet uppermost mantle earthquakes are not observed. Numerous lower-crustal earthquakes occur near the southwestern termination of the Taupo Volcanic Zone (TVZ), an active continental rift in New Zealand. Here we present three-dimensional tomographic imaging of seismic velocities and seismic attenuation in this region using data from a dense seismograph deployment. We find that crustal earthquakes accurately relocated with our three-dimensional seismic velocity model form a continuous band along the rift, deepening from mostly less than 10 km in the central TVZ to depths of 30-40 km in the lower crust, 30 km southwest of the termination of the volcanic zone. These earthquakes often occur in swarms, suggesting fluid movement in critically loaded fault zones. Seismic velocities within the band are also consistent with the presence of fluids, and the deepening seismicity parallels the boundary between high seismic attenuation (interpreted as partial melt) within the central TVZ and low seismic attenuation in the crust to the southwest. This linking of upper and lower-crustal seismicity and crustal structure allows us to propose a common explanation for all the seismicity, involving the weakening of faults on the periphery of an otherwise dry, mafic crust by hot fluids, including those exsolved from underlying melt. Such fluids may generally be an important driver of lower-crustal seismicity near continental rifts.     

Patterns of somatic mutation in human cancer genomes

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.     

Assessing cheatgrass ( Bromus tectorum ) genetic diversity and population structure using RAPD and microsatellite molecular markers

Two molecular marker systems, random amplified polymorphic DNA (RAPD) and microsatellites, were used to evaluate population diversity and differentiation in 4 northern Nevada Bromus tectorum populations. From 80 RAPD primers, we found 16 (20%) that yielded 165 strong repeatable bands. Of those bands, 60 (35.8%) were polymorphic. Of those, 21 met data-pruning guidelines for final analysis. RAPD variation was moderate (0.363, SE = 0.022), ranging from 0.312 to 0.404. Microsatellite variation was similar (0.234, SE = 0.051) but varied more widely, ranging from 0.009 to 0.551. All populations were out of Hardy-Weinberg equilibrium, as expected in a predominantly selfing species. RAPDs revealed significant differentiation (P Bromus rubens ).     

Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD)

Infantile myopathies with diaphragmatic paralysis are genetically heterogeneous, and clinical symptoms do not assist in differentiating between them. We used phased haplotype analysis with subsequent targeted exome sequencing to identify MEGF10 mutations in a previously unidentified type of infantile myopathy with diaphragmatic weakness, areflexia, respiratory distress and dysphagia. MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers, which are greatly reduced in muscle from individuals with early onset myopathy, areflexia, respiratory distress and dysphagia.     

Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations

There is emerging evidence that people with successfully treated HIV infection age prematurely, leading to progressive multi-organ disease, but the reasons for this are not known. Here we show that patients treated with commonly used nucleoside analog anti-retroviral drugs progressively accumulate somatic mitochondrial DNA (mtDNA) mutations, mirroring those seen much later in life caused by normal aging. Ultra-deep re-sequencing by synthesis, combined with single-cell analyses, suggests that the increase in somatic mutation is not caused by increased mutagenesis but might instead be caused by accelerated mtDNA turnover. This leads to the clonal expansion of preexisting age-related somatic mtDNA mutations and a biochemical defect that can affect up to 10% of cells. These observations add weight to the role of somatic mtDNA mutations in the aging process and raise the specter of progressive iatrogenic mitochondrial genetic disease emerging over the next decade.     

Book Reviews

Systemic Practice and Action Research -     

Transferability of tag SNPs in genetic association studies in multiple populations

A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world.     

A worldwide survey of haplotype variation and linkage disequilibrium in the human genome

Recent genomic surveys have produced high-resolution haplotype information, but only in a small number of human populations. We report haplotype structure across 12 Mb of DNA sequence in 927 individuals representing 52 populations. The geographic distribution of haplotypes reflects human history, with a loss of haplotype diversity as distance increases from Africa. Although the extent of linkage disequilibrium (LD) varies markedly across populations, considerable sharing of haplotype structure exists, and inferred recombination hotspot locations generally match across groups. The four samples in the International HapMap Project contain the majority of common haplotypes found in most populations: averaging across populations, 83% of common 20-kb haplotypes in a population are also common in the most similar HapMap sample. Consequently, although the portability of tag SNPs based on the HapMap is reduced in low-LD Africans, the HapMap will be helpful for the design of genome-wide association mapping studies in nearly all human populations.