A mixture model to decompose the heritable basis of complex traits

Pharmacological drugs aim at modulating traits by targeting their causal mechanisms. However, knowledge of such causal mechanisms is scarce and constitutes the main bottleneck in drug development today. To address the issue, the consensus is to associate as many genetic variants as possible to traits of interest in order to then investigate their function and assign them to different mechanisms on that basis. With that purpose, there is an ongoing large-scale coordinated effort to systematically sequence and phenotype larger cohorts of individuals and to map functional elements in the genomes of human cells across tissues. Despite these advances, existing methods do not take full advantage of these increasingly available resources to associate genetic variants to traits and isolate the different mechanisms through which they operate. We have developed a mixture model that integrates multi-trait Genome-Wide Association Study (GWAS) z-scores and functional annotations of Single Nucleotide Polymorphisms (SNPs) to simultaneously boost GWAS power and group together SNPs that likely operate through a similar mechanism. The parameters of the model can be quickly inferred, and we show with realistic simulations that we can recover substantially more true associations than linear regression or a multi-trait GWAS meta-analysis method (MTAG), while recovering the simulated interpretable mixture model components. We applied our model to Coronary Artery Disease (CAD) and Autism Spectrum Disorder (ASD), finding three components for CAD (which point to the regulation of LDL, risk for smoking, and systolic blood pressure, respectively), and a single component for ASD that implicates the fetal and adult brain. Overall, our mixture model constitutes a powerful new framework to integrate the increasingly available functional annotations of the genome and multi-trait GWAS z-scores to uncover the mechanisms that drive complex traits. We expect our method to be progressively insightful as more and better data becomes available. This is expected to be specially true for complex neurodevelopmental disorders like ASD, whose driving mechanisms may only be detectable when considering developmental stage and cell-type specific functional annotations and traits

The wheat Phs-A1 pre-harvest sprouting resistance locus delays the rate of seed dormancy loss and maps 0.3 cM distal to the PM19 genes in UK germplasm

The precocious germination of cereal grains before harvest, also known as pre-harvest sprouting, is an important source of yield and quality loss in cereal production. Pre-harvest sprouting is a complex grain defect and is becoming an increasing challenge due to changing climate patterns. Resistance to sprouting is multi-genic, although a significant proportion of the sprouting variation in modern wheat cultivars is controlled by a few major quantitative trait loci, including Phs-A1 in chromosome arm 4AL. Despite its importance, little is known about the physiological basis and the gene(s) underlying this important locus. In this study, we characterized Phs-A1 and show that it confers resistance to sprouting damage by affecting the rate of dormancy loss during dry seed after-ripening. We show Phs-A1 to be effective even when seeds develop at low temperature (13 °C). Comparative analysis of syntenic Phs-A1 intervals in wheat and Brachypodium uncovered ten orthologous genes, including the Plasma Membrane 19 genes (PM19-A1 and PM19-A2) previously proposed as the main candidates for this locus. However, high-resolution fine-mapping in two bi-parental UK mapping populations delimited Phs-A1 to an interval 0.3 cM distal to the PM19 genes. This study suggests the possibility that more than one causal gene underlies this major pre-harvest sprouting locus. The information and resources reported in this study will help test this hypothesis across a wider set of germplasm and will be of importance for breeding more sprouting resilient wheat varieties

Conducción eléctrica entre Aurícula izquierda y Venas pulmonares: Caracterización mediante mapeo de alta densidad

La conexión eléctrica entre las venas pulmonares (VVPP) y el antro auricular no ocurre en todo el perímetro de la vena sino en zonas de conducción preferencial (ZCP). Los sistemas de mapeo de actividad eléctrica de alta densidad permite distinguirlos de forma exacta. El objetivo consiste en determinar la presencia de ZCP, su número, características anatómicas y localización, así como objetivar la existencia de similitudes entre las características anatómicas de dichas zonas.The electrical connection between the pulmonary veins and the atrial antrum doesn´t occur around the entire perimeter of the vein but in preferential conduction zones (PCZ). The high-density cardiac electrical activity mapping systems allow to distinguish them exactly. The objective is to determine the presence of PCZ, their number, anatomical characteristics and location, as well as to objectify the existence of similarities between the anatomical characteristics of these zones.Medicin

Moderasi Beragama Karaeng Galesong XVI (Studi Kasus Penerimaan Pendatang Tionghoa dan Pembangunan Klenteng di Galesong)

Berdasarkan hasil penelitian, menunjukkan adanya praktek-praktek moderasi beragama yang dilakukan oleh Karaeng Galesong ke XVI, mulai dari kedatangan Masyarakat Tionghoa baik dari jalur Luwu maupun Makassar yang tiba di Galesong, sampai pada pendirian klenteng. Pendirian klenteng tersebut merupakan bentuk nyata dari praktik moderasi beragama yang ditunjukkan oleh Karaeng Galesong ke XVI. Praktik moderasi beragama Karaeng Galesong ke XVI dibaca berdasarkan tiga indikator moderasi beragama, yaitu komitmen multikultural dan kebangsaan, toleransi beragama dan sikap akomodatif terhadap kebudayaan lokal. Implikasi dari penelitian tesis ini, terdapat lima poin. Pertama, penguatan moderasi beragama dengan berlandaskan sejarah lokal agar program moderasi beragama memiliki akar historis dalam khazanah sosial dan budaya lokal. Kedua, pengarusutamaan moderasi beragama menjadikan pendekatan kearifan lokal sebagai modal sosial dan kultural. Ketiga, penguatan moderasi beragama harus bersinergi dengan kebijakan multikultural sebagaimana yang dijalankan oleh Karaeng Galesong ke XVI. Keempat, pelestarian Klenteng Pan Ko Ong sebagai saksi sejarah best practice pembauran masyarakat pendatang Tionghoa dan penerimaan oleh pemimpin dan masyarakat Galesong. Kelima, menjadikan Klenteng Pan Ko Ong sebagai simbol moderasi beragama di Galesong khususnya dan di Kabupaten Takalar secara umum

Nutrition Management in a Training Camp

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Nutrition Management in a Training Camp (Part 2)

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About the present conditions of sports players of nutrition

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Food service worker is related research (Work, tired state and meal research)

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ブンキサアミノサン ニ ヨル ラット ノ ジハツ ワマワシ ウンドウリョウ オヨビ ニッシュウ リズム ニ タイスル コウカ ニ ツイテ II

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