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The field of cancer genomics has been transformed by recent advances in sequencing and the development of new computational methods. This Review outlines the available cancer genomics software and describes recent insights gained from the application of these tools.
Among rodent species, there is a wide diversity in lifespans and cancer susceptibilities, which makes comparative studies of rodents an attractive strategy for identifying molecular mechanisms that underlie ageing and cancer. This Review describes the various biological insights provided by comparative rodent genomics, including those from whole-genome sequencing of long-lived and highly cancer-resistant species. Such progress has potential implications for understanding and modulating human disease.
Mutagenic processes leave characteristic imprints on the cancer genome that can help to identify the underlying DNA damaging components as well as DNA repair and replicative pathways that are active or disrupted. This Review discusses these mutational signatures according to different classes of mutations and summarizes how different components contribute mechanistically to produce each signature type.
Imprinted genes influence a wide range of biological processes, the effects of which extend from prenatal stages to adulthood. This Review discusses the role of imprinted genes, with a focus on postnatal and adult phenotypes, and their contribution to common diseases such as intrauterine growth restriction, obesity, psychiatric disorders and cancer.
The role of telomeric factors as guardians of chromosome ends from threats to genome integrity (such as degradation and inappropriate DNA damage response activation) has long been appreciated. This Review discusses the extratelomeric activity of these factors and how they can regulate the transcription of genes involved in metabolism, immunity and differentiation.
Gene-regulatory DNA elements control complex spatiotemporal patterns of gene expression, and alterations to these sequences are commonly associated with inter-individual phenotypic variation and human disease. This Review discusses our latest understanding of how different layers of information in these sequences control the binding of regulators and influence gene expression outcomes.
A central topic in biology concerns how genotypes determine phenotypes and functions of organisms that affect their evolutionary fitness. This Review discusses recent advances in the development of empirical fitness landscapes and their contribution to theoretical analyses of the predictability of evolution.
Recent technological advances have enabled the probing of RNA structure across the transcriptomes of various speciesin vitro and in vivo. This Review discusses our latest understanding of how RNA structure influences various steps of gene expression, including translation, mRNA localization and microRNA-mediated gene regulation.
RNA-directed DNA methylation (RdDM) is a major mechanism of transcriptional gene silencing in plants that is mediated through small interfering RNAs (siRNAs) and plant-specific RNA polymerases. This Review summarizes our latest understanding of RdDM, including its genomic targets, molecular mechanisms (such as emerging non-canonical pathways) and diverse biological roles.
Data sharing in genetics is essential to ensure research progress. However, concerns about the impact on privacy of data originators have been raised. This Review summarizes privacy breaching strategies and potential mitigation methods for privacy-preserving dissemination of sensitive data, and highlights different cases that are relevant to genetic applications.
The impact of various infectious agents on human survival and reproduction over thousands of years has exerted selective pressure on numerous regions of the human genome. This Review describes how such signatures of selection can be detected and integrated with data from complementary approaches, such as genome-wide association studies, to provide biological insights into host–pathogen interactions.
This Review discusses the principles and applications of significance testing and power calculation, including recently proposed gene-based tests for rare variants.
The complex mechanisms that regulate the X chromosome lead to evolutionary and physiological variability in gene expression between species, the sexes, individuals, developmental stages, tissues and cell types. This Review discusses the causes and consequences of variability in X-linked gene expression.
Whole-genome assemblies of humans and non-human primates are yielding data on the evolutionary origins of the human genome, as well as insights into genetic similarities and differences between species used as models for disease-related research. This Review discusses current knowledge and opportunities for comparative primate genomics created by recent advances in genome sequencing technologies.
Programmable nucleases — including ZFNs, TALENs and RGENs derived from the prokaryotic CRISPR–Cas system — enable targeted high-precision genome engineering. This Review summarizes current knowledge of nuclease-specific features, individual pros and cons, and approaches to improve the efficiency of these enzymes to help researchers to choose the most appropriate tool for various genome editing experiments and applications.
This Review describes how genomic technologies are providing novel insights intoMycobacterium tuberculosis, which is the causative agent of human tuberculosis. There has been progress in understanding the ancient evolutionary history of human-adapted M. tuberculosis, mutations underlying strain diversity and drug resistance, and the host–pathogen molecular interactions.
Diverse types of RNA in various species are modified by methylation to formN6-methyladenosine (m6A). This Review describes how progress in the characterization of m6A distributions and of proteins that 'write', 'erase' and 'read' this mark is revealing roles for reversible m6A methylation in dynamic gene expression control.
Enhancers are DNA elements that are key regulators of gene expression, but their complexities and context dependence makes their identification and characterization challenging. This Review discusses how an improved understanding of the varied properties of enhancers is being used in diverse approaches for the systematic prediction of enhancers genome wide.
This Review discusses cryptic genetic variation and focuses particularly on empirical support for widespread cryptic genetic variation in natural populations, its potential role in human diseases and its contribution to evolution.
CCCTC-binding factor (CTCF) is a DNA-binding protein that has various, often seemingly contradictory, roles in gene regulation. This Review describes these disparate functions and how the context-dependent looping of DNA regions by CTCF is emerging as a potential unifying mechanism that underpins these diverse roles.
