Authors: Laura M. Zahn, John Travis

How much do your eyes water when cutting onions? Does fresh cilantro taste like soap to you? Do you have stretch marks on your hips, thighs, or the backs of your arms? Have you ever been diagnosed with brain cancer? Mail off your spit for a $99 genetic analysis from 23andMe, and you will get information about your ancestry, served up on a web account. You will also encounter a list of optional survey questions. A lot of survey questions. Some are quirky queries about your tastes and habits. Others are intimate probes into your experiences with disease and medicine. Author: Kelly Servick

As DNA sequencing gets cheaper, more and more organizations, companies, and countries are amassing computer server–busting amounts of human DNA data, typically for studies of the links between genes, lifestyle factors and disease risk. Science's informal survey found at least 17 biobanks that hold—or plan to hold—genomic data on 75,000 or more people who have volunteered to share their health information for research. The data range from scans of common mutations known as single nucleotide polymorphisms (SNPs) to the protein-coding portions (exomes) to whole genome sequences. Here we have highlighted many of these efforts taking shape across the globe. Author: Jocelyn Kaiser

Germline mutations are the principal cause of heritable disease and the ultimate source of evolutionary change. Similarly, somatic mutations are the primary cause of cancer and may contribute to the burden of human disease more broadly than previously appreciated. Here, we review recent insights into the rates, spectrum, and determinants of genomic mutations and how these parameters inform our understanding of both Mendelian and complex human diseases. We also consider models for conceptualizing mutational consequences and outline several key areas for future research, including the development of new technologies to access and quantify the full spectrum of mutations, as well as to better interpret the consequences of mutations with respect to molecular functionality, evolutionary fitness, and disease pathogenicity. Authors: Jay Shendure, Joshua M. Akey

Spontaneously occurring mutations accumulate in somatic cells throughout a person’s lifetime. The majority of these mutations do not have a noticeable effect, but some can alter key cellular functions. Early somatic mutations can cause developmental disorders, whereas the progressive accumulation of mutations throughout life can lead to cancer and contribute to aging. Genome sequencing has revolutionized our understanding of somatic mutation in cancer, providing a detailed view of the mutational processes and genes that drive cancer. Yet, fundamental gaps remain in our knowledge of how normal cells evolve into cancer cells. We briefly summarize a number of the lessons learned over 5 years of cancer genome sequencing and discuss their implications for our understanding of cancer progression and aging. Authors: Iñigo Martincorena, Peter J. Campbell

Large-scale genomic investigations have just begun to illuminate the molecular genetic contributions to major psychiatric illnesses, ranging from small-effect-size common variants to larger-effect-size rare mutations. The findings provide causal anchors from which to understand their neurobiological basis. Although these studies represent enormous success, they highlight major challenges reflected in the heterogeneity and polygenicity of all of these conditions and the difficulty of connecting multiple levels of molecular, cellular, and circuit functions to complex human behavior. Nevertheless, these advances place us on the threshold of a new frontier in the pathophysiological understanding, diagnosis, and treatment of psychiatric disease. Authors: Daniel H. Geschwind, Jonathan Flint

Mitochondrial diseases are among the most common and most complex of all inherited genetic diseases. The involvement of both the mitochondrial and nuclear genome presents unique challenges, but despite this there have been some remarkable advances in our knowledge of mitochondrial diseases over the past few years. A greater understanding of mitochondrial genetics has led to improved diagnosis as well as novel ways to prevent transmission of severe mitochondrial disease. These and other advances have had a major impact on patient care, but considerable challenges remain, particularly in the areas of therapies for those patients manifesting clinical symptoms associated with mitochondrial dysfunction and the tissue specificity seen in many mitochondrial disorders. This review highlights some important recent advances in mitochondrial disease but also stresses the areas where progress is essential. Authors: Robert N. Lightowlers, Robert W. Taylor, Doug M. Turnbull

Author: Jelena Stajic

Author: Stella M. Hurtley

Author: Valda Vinson

Author: Phil Szuromi

Author: Ian S. Osborne

Author: John F. Foley

Author: Sacha Vignieri

Author: Angela Colmone

Author: L. Bryan Ray

Author: Jake Yeston

Author: Marc S. Lavine

Author: Jake Yeston