Catálogo de publicaciones - revistas

<jats:p>Sequencing every newborn’s genome to detect diseases faces ethical and practical obstacles, but the United Kingdom is pushing ahead with a major test</jats:p>

<jats:p>Over the next decade, the primary challenge in human genetics will be to understand the biological mechanisms by which genetic variants influence phenotypes, including disease risk. Although the scale of this challenge is daunting, better methods for functional variant interpretation will have transformative consequences for disease diagnosis, risk prediction, and the development of new therapies. An array of new methods for characterizing variant impact at scale, using patient tissue samples as well as in vitro models, are already being applied to dissect variant mechanisms across a range of human cell types and environments. These approaches are also increasingly being deployed in clinical settings. We discuss the rationale, approaches, applications, and future outlook for characterizing the molecular and cellular effects of genetic variants.</jats:p>

<jats:p>The sequencing of the human genome has allowed the study of the genetic architecture of common diseases: the number of genomic variants that contribute to risk of disease and their joint frequency and effect size distribution. Common diseases are polygenic, with many loci contributing to phenotype, and the cumulative burden of risk alleles determines individual risk in conjunction with environmental factors. Most risk loci occur in noncoding regions of the genome regulating cell- and context-specific gene expression. Although the effect sizes of most risk alleles are small, their cumulative effects in individuals, quantified as a polygenic (risk) score, can identify people at increased risk of disease, thereby facilitating prevention or early intervention.</jats:p>

<jats:p>Cancer is a major cause of global mortality underpinned by genomic and epigenomic derangements. Here, we highlight the importance of multimodal data integration in understanding the molecular evolution of malignant cell states across the cancer life cycle. The widespread presence of driver mutations and epigenetic alterations in normal-appearing tissues is prompting a reassessment of how cancer initiation is defined. In later-stage cancers, studying the roles of clonal selection, epigenomic adaptation, and persister cells in metastasis and therapy resistance is an emerging field. Finally, the importance of tumor ecosystems in driving cancer development is being unraveled by single-cell and spatial technologies at unprecedented resolution. Improving cancer risk assessment and accelerating therapeutic discovery for patients will require robust, comprehensive, and integrated temporal, spatial, and multilevel tumor atlases across the cancer life cycle.</jats:p>

<jats:p>Recent advancements in DNA sequencing technologies and laboratory preparation protocols have rapidly expanded the scope of ancient DNA research over the past decade, both temporally and geographically. Discoveries include interactions between archaic and modern humans as well as modern human population dynamics, including those coinciding with the Last Glacial Maximum and the settlement history of most world regions. This new type of data allows us to examine the deep past of human population dynamics and sharpen the current understanding of our present. The continued development in the ancient DNA field has transformed our understanding of human genetic history and will keep uncovering the further mysteries of our recent evolutionary past.</jats:p>

<jats:p> Highlights from the <jats:italic>Science</jats:italic> family of journals </jats:p>

<jats:p>Editors’ selections from the current scientific literature</jats:p>

<jats:title>Tracing a path to ethylene</jats:title> <jats:p> Ethylene is produced industrially from fossil carbon sources, but plants and microbes produce small amounts through a handful of unusual enzymatic reactions. Copeland <jats:italic>et al</jats:italic> . studied a microbial ethylene-forming enzyme using oxygen isotope–tracing experiments and biochemical assays to test mechanistic proposals. This enzyme, which uses a non–heme iron center to activate oxygen, catalyzes two distinct oxidation reactions with different mechanisms. One reaction is entirely off-pathway and results in fragmentation of a co-substrate, arginine. The other reaction can completely fragment 2-oxoglutarate into ethylene, bicarbonate, and two molecules of carbon dioxide; however, it occasionally derails and yields an omega–hydroxy acid product. —MAF </jats:p>

<jats:title>Silicon anode solid-state batteries</jats:title> <jats:p> Research on solid-state batteries has focused on lithium metal anodes. Alloy-based anodes have received less attention in part due to their lower specific capacity even though they should be safer. Tan <jats:italic>et al</jats:italic> . developed a slurry-based approach to create films from micrometer-scale silicon particles that can be used in anodes with carbon binders. When incorporated into solid-state batteries, they showed good performance across a range of temperatures and excellent cycle life in full cells. —MSL </jats:p>

<jats:title>Repeats associated with phenotype</jats:title> <jats:p> The degree to which repeated sequences within a genome affect human phenotypes has been difficult to establish. Mukamel <jats:italic>et al</jats:italic> . examined thousands of genomes in the UK Biobank and found that some of the largest effects of common genetic variants on human phenotypes, including those with clinical relevance, arise from protein-coding repeat polymorphisms (see the Perspective by Gymrek and Goren). Mapping the effects of the size and copy number of these repeated protein domains links genetic variation to human phenotypes, including lipoprotein(a) concentration, height, and male pattern balding. Furthermore, the alleles and frequencies of these repeated sequences differ between individuals of African and European descent, resulting in differences between the populations with clinical relevance for traits including lipoprotein(a) levels, a risk factor for coronary artery disease. —LMZ </jats:p>