Comparative Linkage Meta-Analysis Reveals Regionally-Distinct, Disparate Genetic Architectures: Application to Bipolar Disorder and Schizophrenia

New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for ”missing heritability.” However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS), alternative approaches robust to detection of low-frequency (1–5% MAF) and rare (<1%) variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods—GSMA and MSP—applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA) may be used to optimize low-frequency and rare variant discovery in the modern genomic era

Active Tectonics Around Almaty and along the Zailisky Alatau Rangefront

This is the author accepted manuscript. The final version is available from Wiley via http://onlinelibrary.wiley.com/doi/10.1002/2017TC004657/abstractThe Zailisky Alatau is a >250-km-long mountain range in Southern Kazakhstan. Its northern rangefront around the major city of Almaty has more than 4 km topographic relief, yet in contrast to other large mountain fronts in the Tien Shan, little is known about its Late Quaternary tectonic activity despite several destructive earthquakes in the historical record. We analyse the tectonic geomorphology of the rangefront fault using field observations, differential GPS measurements of fault scarps, historical and recent satellite imagery, metre-scale topography derived from stereo satellite images, and decimetre-scale elevation models from UAV surveys. Fault scarps ranging in height from ~2 m to >20 m in alluvial fans indicate surface rupturing earthquakes occurred along the rangefront fault since the Last Glacial Maximum (LGM). Minimum estimated magnitudes for those earthquakes are M6.8- 7. Radiocarbon dating results from charcoal layers in uplifted river terraces indicate a Holocene slip rate of ~1.2-2.2 mm/a. We find additional evidence for active tectonic deformation all along the Almaty rangefront, basinward in the Kazakh platform, and in the interior of the Zailisky mountain range. Our data indicate the seismic hazard faced by Almaty comes from a variety of sources, and we emphasize the problems related to urban growth into the loess-covered foothills and secondary earthquake effects. With our structural and geochronologic framework we present a schematic evolution of the Almaty rangefront that may be applicable to similar settings of tectonic shortening in the mountain ranges of Central Asia

Phylotranscriptomic insights into the diversification of endothermic Thunnus tunas

Birds, mammals, and certain fishes, including tunas, opahs and lamnid sharks, are endothermic, conserving internally generated, metabolic heat to maintain body or tissue temperatures above that of the environment. Bluefin tunas are commercially important fishes worldwide, and some populations are threatened. They are renowned for their endothermy, maintaining elevated temperatures of the oxidative locomotor muscle, viscera, brain and eyes, and occupying cold, productive high-latitude waters. Less cold-tolerant tunas, such as yellowfin tuna, by contrast, remain in warm-temperate to tropical waters year-round, reproducing more rapidly than most temperate bluefin tuna populations, providing resiliency in the face of large-scale industrial fisheries. Despite the importance of these traits to not only fisheries but also habitat utilization and responses to climate change, little is known of the genetic processes underlying the diversification of tunas. In collecting and analyzing sequence data across 29,556 genes, we found that parallel selection on standing genetic variation is associated with the evolution of endothermy in bluefin tunas. This includes two shared substitutions in genes encoding glycerol-3 phosphate dehydrogenase, an enzyme that contributes to thermogenesis in bumblebees and mammals, as well as four genes involved in the Krebs cycle, oxidative phosphorylation, β-oxidation, and superoxide removal. Using phylogenetic techniques, we further illustrate that the eight Thunnus species are genetically distinct, but found evidence of mitochondrial genome introgression across two species. Phylogeny-based metrics highlight conservation needs for some of these species

Word boundary modelling and full covariance gaussians for Arabic Speech-to-Text systems

This paper describes recent improvements to the Cambridge Arabic Large Vocabulary Continuous Speech Recognition (LVCSR) Speech-to-Text (STT) system. It is shown that wordboundary context markers provide a powerful method to enhance graphemic systems by implicit phonetic information, improving the modelling capability of graphemic systems. In addition, a robust technique for full covariance Gaussian modelling in the Minimum Phone Error (MPE) training framework is introduced. This reduces the full covariance training to a diagonal covariance training problem, thereby solving related robustness problems. The full system results show that the combined use of these and other techniques within a multi-branch combination framework reduces the Word Error Rate (WER) of the complete system by up to 5.9% relative. Copyright © 2011 ISCA

Multi-systemic evaluation of biological and emotional responses to the Trier Social Stress Test : a meta-analysis and systematic review

202310 bcvcVersion of RecordRGCOthersOpen Fund from the Guangdong-Hong Kong-Macau Greater Bay Area Centre for Brain Science and Brain-Inspired Intelligence (2019007) to R. Shao.Publishe