All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band

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

All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

Astro2020 APC White PaperThe All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes

Identifying genetic risk factors for highly heterogeneous disorders such as epilepsy remains challenging. Here we present, to our knowledge, the largest whole-exome sequencing study of epilepsy to date, with more than 54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies and generalized and focal epilepsies, whereas most other gene discoveries are subtype specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single-nucleotide/short insertion and deletion variants, copy number variants and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies