Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Demonstration of anticoagulation patient self-testing feasibility at an Indian Health Service facility: a case series analysis

Background: Anticoagulation patient self-testing (PST) represents an alternative approach to warfarin monitoring by enabling patients to use coagulometers to test their international normalized ratio (INR) values. PST offers several advantages that potentially improve warfarin management. Objective: To describe implementation and associated performance of a PST demonstration program at an Indian Health Service (IHS) facility. Methods: A non-consecutive case series analysis of patients from a pharmacy-managed PST demonstration program was performed at an IHS facility in Oklahoma between July 2008 and February 2009. Results: Mean time in therapeutic range (TTR) for the seven patients showed a small, absolute increase during the twelve weeks of PST compared to the twelve weeks prior to PST. Four of the seven patients had an increase in TTR during the twelve week course of PST compared to their baseline TTR. Three of four patients with increased TTR in the final eight week period of PST achieved a TTR of 100%. Of the three patients who experienced a decrease in TTR after initiating self-testing, two initially presented with a TTR of 100% prior to PST and one patient had a TTR of 100% for the final eight weeks of PST. The two patients not achieving a TTR of 100% during the twelve week PST period demonstrated an increase in TTR following the first four weeks of PST. Conclusion: Although anticoagulation guidelines now emphasize patient self-management (PSM) only, optimal PST remains an integral process in PSM delivery. In the patients studied, the results of this analysis suggest that PST at the IHS facility provided a convenient, alternative method for management of chronic warfarin therapy for qualified patients. More than half of the patients demonstrated improvement in TTR. Although there is a learning curve immediately following PST initiation, the mean TTR for the entire PST period increased modestly when compared to the time period prior to PST.Antecedentes: La automedición por el paciente (PST) de la anticoagulación representa un abordaje alternativo a la monitorización de warfarina al capacitar a los pacientes a utilizar coagulómetros para medir los valores de su ratio internacional normalizado (RIN). La PST ofrece varias ventajas que mejoran el manejo de warfarina. Objetivo: describir la implantación y la actuación asociada a un programa de demostración de PST en un centro del Servicio Sanitario Indio. Métodos: Se realizó un análisis de una serie de casos no consecutivos de un programa de PST realizado por una farmacia en un Servicio Sanitario Indio de Oklahoma desde julio 2008 a Febrero 2009. Resultados: El tiempo medio en rango terapéutico (TRT) para los siete pacientes mostró un pequeño incremento absoluto durante los 12 meses de PST comparado con los 12 meses previos al PST. Cuatro de los siete pacientes tuvieron un aumento de TRT durante las 12 semanas de tratamiento comparado con el TRT al inicio. Tres de los cuatro con aumento de TRT, alcanzaron un TRT del 100% al final del periodo de 8 semanas. De los tres pacientes que tuvieron un descenso de TRT después de inicial la automedición, dos presentaban un TRT antes del PST del 100% y un paciente tenía un TRT del 100% al final de las 8 semanas de PST. Los dos pacientes que no alcanzaron un TRT del 100% durante las 12 semanas de PST demostraron un aumento de TRT después de las 4 semanas iniciales. Conclusión: Aunque las guias de anticoagulación actualmente solo enfatizan el auto-manejo por el paciente, el PST optimo es parte integral de ese auto-manejo En los pacientes estudiados, los resultados de este análisis sugieren que el PST en un centro del Servicio Sanitario Indio proporciona un método conveniente y alternativo para el manejo crónico del tratamiento con warfarina en pacientes cualificados. Más de la mitad de los pacientes demostró un aumento del TRT. Aunque existe una curva de aprendizaje inmediatamente después de la iniciación del PST, la media de TRT para el periodo completo de PST aumentó modestamente comparada con el tiempo anterior al PST

A systems genetics resource and analysis of sleep regulation in the mouse

<div><p>Sleep is essential for optimal brain functioning and health, but the biological substrates through which sleep delivers these beneficial effects remain largely unknown. We used a systems genetics approach in the BXD genetic reference population (GRP) of mice and assembled a comprehensive experimental knowledge base comprising a deep “sleep-wake” phenome, central and peripheral transcriptomes, and plasma metabolome data, collected under undisturbed baseline conditions and after sleep deprivation (SD). We present analytical tools to interactively interrogate the database, visualize the molecular networks altered by sleep loss, and prioritize candidate genes. We found that a one-time, short disruption of sleep already extensively reshaped the systems genetics landscape by altering 60%–78% of the transcriptomes and the metabolome, with numerous genetic loci affecting the magnitude and direction of change. Systems genetics integrative analyses drawing on all levels of organization imply α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and fatty acid turnover as substrates of the negative effects of insufficient sleep. Our analyses demonstrate that genetic heterogeneity and the effects of insufficient sleep itself on the transcriptome and metabolome are far more widespread than previously reported.</p></div