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  • Development: Transcriptomic blueprints
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Linda Koch

    Development: Transcriptomic blueprints Nature Reviews Genetics, Published online: 18 September 2017; doi:10.1038/nrg.2017.77

    更新日期:2017-09-19
  • Development: Transcriptomic blueprints
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Linda Koch

    Development: Transcriptomic blueprints Nature Reviews Genetics, Published online: 18 September 2017; doi:10.1038/nrg.2017.77

    更新日期:2017-09-19
  • Chromosome biology: Different turfs for cohesin and condensin
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Eytan Zlotorynski

    The structural maintenance of chromosomes (SMC) complexes cohesin and condensin are ring-shaped protein machines that encircle the chromatin and control various aspects of chromosome function, including the formation of chromatin loops, sister chromatid cohesion and mitotic chromosome compaction. Schalbetter et al. now show that

    更新日期:2017-09-15
  • Model organisms: New tools, new insights — probing social behaviour in ants
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Dorothy Clyde

    Eusocial insects display complex social behaviours, but the underlying molecular mechanisms are largely unknown. Now, a trio of papers in Cell decribe two genes (orco and corazonin) that control social behaviour in ants. Furthermore, two of the studies describe the first

    更新日期:2017-09-15
  • Pathogen genetics: Evolutionary dynamics driving drug resistance
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-14
    Linda Koch

    The broad application of antibiotics is responsible for the development of antimicrobial resistance in many bacterial pathogens. Two recent studies now reconstruct the evolutionary history of the first methicillin-resistant Staphylococcus aureus (MRSA) and the multidrug-resistant Escherichia coli lineage ST131. Harkins et al.

    更新日期:2017-09-15
  • Genetic engineering: Pigs without PERVs
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Linda Koch

    Pig-to-human organ transplantation holds promise for resolving the existing shortage of transplantable organs, but the potential transmission risk of porcine endogenous retroviruses (PERVs) to humans has remained a concern. Now, Niu et al. report the successful generation of PERV-inactivated pigs by somatic cell nuclear

    更新日期:2017-09-15
  • Gene therapy: Human genome editing in heart disease
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Gregory B. Lim

    Human germline genome editing with CRISPR–Cas9 was used with high efficiency, accuracy and safety to correct a heterozygous, autosomal dominant mutation in MYBPC3 associated with hypertrophic cardiomyopathy, according to a new study in Nature.CRISPR–Cas9 is a versatile tool for recognizing a specific

    更新日期:2017-09-15
  • Evolutionary biology through the lens of budding yeast comparative genomics
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-17
    Souhir Marsit, Jean-Baptiste Leducq, Éléonore Durand, Axelle Marchant, Marie Filteau, Christian R. Landry

    The budding yeast Saccharomyces cerevisiae is a highly advanced model system for studying genetics, cell biology and systems biology. Over the past decade, the application of high-throughput sequencing technologies to this species has contributed to this yeast also becoming an important model for evolutionary genomics. Indeed, comparative genomic analyses of laboratory, wild and domesticated yeast populations are providing unprecedented detail about many of the processes that govern evolution, including long-term processes, such as reproductive isolation and speciation, and short-term processes, such as adaptation to natural and domestication-related environments.

    更新日期:2017-09-15
  • Settling the score: variant prioritization and Mendelian disease
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Karen Eilbeck, Aaron Quinlan, Mark Yandell

    When investigating Mendelian disease using exome or genome sequencing, distinguishing disease-causing genetic variants from the multitude of candidate variants is a complex, multidimensional task. Many prioritization tools and online interpretation resources exist, and professional organizations have offered clinical guidelines for review and return of prioritization results. In this Review, we describe the strengths and weaknesses of widely used computational approaches, explain their roles in the diagnostic and discovery process and discuss how they can inform (and misinform) expert reviewers. We place variant prioritization in the wider context of gene prioritization, burden testing and genotype–phenotype association, and we discuss opportunities and challenges introduced by whole-genome sequencing.

    更新日期:2017-09-15
  • Synthetic lethality and cancer
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-26
    Nigel J. O'Neil, Melanie L. Bailey, Philip Hieter

    A synthetic lethal interaction occurs between two genes when the perturbation of either gene alone is viable but the perturbation of both genes simultaneously results in the loss of viability. Key to exploiting synthetic lethality in cancer treatment are the identification and the mechanistic characterization of robust synthetic lethal genetic interactions. Advances in next-generation sequencing technologies are enabling the identification of hundreds of tumour-specific mutations and alterations in gene expression that could be targeted by a synthetic lethality approach. The translation of synthetic lethality to therapy will be assisted by the synthesis of genetic interaction data from model organisms, tumour genomes and human cell lines.

    更新日期:2017-09-15
  • Dissecting evolution and disease using comparative vertebrate genomics
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-24
    Jennifer R. S. Meadows, Kerstin Lindblad-Toh

    With the generation of more than 100 sequenced vertebrate genomes in less than 25 years, the key question arises of how these resources can be used to inform new or ongoing projects. In the past, this diverse collection of sequences from human as well as model and non-model organisms has been used to annotate the human genome and to increase the understanding of human disease. In the future, comparative vertebrate genomics in conjunction with additional genomic resources will yield insights into the processes of genome function, evolution, speciation, selection and adaptation, as well as the quantification of species diversity. In this Review, we discuss how the genomics of non-human organisms can provide insights into vertebrate biology and how this can contribute to the understanding of human physiology and health.

    更新日期:2017-09-15
  • Harnessing ancient genomes to study the history of human adaptation
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Stephanie Marciniak, George H. Perry

    The past several years have witnessed an explosion of successful ancient human genome-sequencing projects, with genomic-scale ancient DNA data sets now available for more than 1,100 ancient human and archaic hominin (for example, Neandertal) individuals. Recent 'evolution in action' analyses have started using these data sets to identify and track the spatiotemporal trajectories of genetic variants associated with human adaptations to novel and changing environments, agricultural lifestyles, and introduced or co-evolving pathogens. Together with evidence of adaptive introgression of genetic variants from archaic hominins to humans and emerging ancient genome data sets for domesticated animals and plants, these studies provide novel insights into human evolution and the evolutionary consequences of human behaviour that go well beyond those that can be obtained from modern genomic data or the fossil and archaeological records alone.

    更新日期:2017-09-11
  • Chromatin: Probing a piRNA paradox
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Darren J. Burgess

    Chromatin: Probing a piRNA paradox Nature Reviews Genetics, Published online: 11 September 2017; doi:10.1038/nrg.2017.76

    更新日期:2017-09-11
  • Harnessing ancient genomes to study the history of human adaptation
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Stephanie Marciniak, George H. Perry

    The past several years have witnessed an explosion of successful ancient human genome-sequencing projects, with genomic-scale ancient DNA data sets now available for more than 1,100 ancient human and archaic hominin (for example, Neandertal) individuals. Recent 'evolution in action' analyses have started using these data sets to identify and track the spatiotemporal trajectories of genetic variants associated with human adaptations to novel and changing environments, agricultural lifestyles, and introduced or co-evolving pathogens. Together with evidence of adaptive introgression of genetic variants from archaic hominins to humans and emerging ancient genome data sets for domesticated animals and plants, these studies provide novel insights into human evolution and the evolutionary consequences of human behaviour that go well beyond those that can be obtained from modern genomic data or the fossil and archaeological records alone.

    更新日期:2017-09-11
  • Chromatin: Probing a piRNA paradox
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Darren J. Burgess

    Chromatin: Probing a piRNA paradox Nature Reviews Genetics, Published online: 11 September 2017; doi:10.1038/nrg.2017.76

    更新日期:2017-09-11
  • Beyond editing to writing large genomes
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Raj Chari, George M. Church

    Beyond editing to writing large genomes Nature Reviews Genetics, Published online: 30 August 2017; doi:10.1038/nrg.2017.59 Advances in genome sequencing, editing and synthetic biology have enhanced the feasibility of large-scale genome engineering, termed genome writing. In this Opinion article, Chari and Church discuss the strengths and limitations of diverse strategies for genome writing, including extensively modifying existing genomes versus synthesizing genomes de novo, and they provide future visions for writing large genomes.

    更新日期:2017-09-04
  • Human genetic variation and the gut microbiome in disease
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Andrew Brantley Hall, Andrew C. Tolonen, Ramnik J. Xavier

    Taxonomic and functional changes to the composition of the gut microbiome have been implicated in multiple human diseases. Recent microbiome genome-wide association studies reveal that variants in many human genes involved in immunity and gut architecture are associated with an altered composition of the gut microbiome. Although many factors can affect the microbial organisms residing in the gut, a number of recent findings support the hypothesis that certain host genetic variants predispose an individual towards microbiome dysbiosis. This condition, in which the normal microbiome population structure is disturbed, is a key feature in disorders of metabolism and immunity.

    更新日期:2017-09-04
  • Vertebrate sex determination: evolutionary plasticity of a fundamental switch
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Blanche Capel

    The discovery of the Sry gene in 1990 triggered a revolution in our understanding of sex determination. More recently, advances in non-model organisms have been fuelled by the rapid evolution of affordable genome and transcriptome technologies. This Review considers the unusual plasticity in the bipotential system of sex determination and some of the diverse mechanisms that have evolved to control this critical developmental decision, including strong genetic pathways, environmental influences and epigenetic regulation. Ideas emerging from model and non-model organisms that suggest that sex determination operates as an antagonistic network with the emergent property of bistability are discussed.

    更新日期:2017-09-04
  • Beyond editing to writing large genomes
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-30
    Raj Chari, George M. Church

    Beyond editing to writing large genomes Nature Reviews Genetics, Published online: 30 August 2017; doi:10.1038/nrg.2017.59 Advances in genome sequencing, editing and synthetic biology have enhanced the feasibility of large-scale genome engineering, termed genome writing. In this Opinion article, Chari and Church discuss the strengths and limitations of diverse strategies for genome writing, including extensively modifying existing genomes versus synthesizing genomes de novo, and they provide future visions for writing large genomes.

    更新日期:2017-09-04
  • Chromosome biology: Different turfs for cohesin and condensin
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Eytan Zlotorynski

    Chromosome biology: Different turfs for cohesin and condensin Nature Reviews Genetics, Published online: 30 August 2017; doi:10.1038/nrg.2017.71

    更新日期:2017-09-04
  • Genetic engineering: Pigs without PERVs
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Linda Koch

    Genetic engineering: Pigs without PERVs Nature Reviews Genetics, Published online: 30 August 2017; doi:10.1038/nrg.2017.73

    更新日期:2017-09-04
  • Model organisms: New tools, new insights — probing social behaviour in ants
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Dorothy Clyde

    Model organisms: New tools, new insights — probing social behaviour in ants Nature Reviews Genetics, Published online: 30 August 2017; doi:10.1038/nrg.2017.70

    更新日期:2017-09-04
  • Human genetic variation and the gut microbiome in disease
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-21
    Andrew Brantley Hall, Andrew C. Tolonen, Ramnik J. Xavier

    Taxonomic and functional changes to the composition of the gut microbiome have been implicated in multiple human diseases. Recent microbiome genome-wide association studies reveal that variants in many human genes involved in immunity and gut architecture are associated with an altered composition of the gut microbiome. Although many factors can affect the microbial organisms residing in the gut, a number of recent findings support the hypothesis that certain host genetic variants predispose an individual towards microbiome dysbiosis. This condition, in which the normal microbiome population structure is disturbed, is a key feature in disorders of metabolism and immunity.

    更新日期:2017-09-04
  • Gene therapy: Human genome editing in heart disease
    Nat. Rev. Genet. (IF 40.282) Pub Date : 
    Gregory B. Lim

    Gene therapy: Human genome editing in heart disease Nature Reviews Genetics, Published online: 21 August 2017; doi:10.1038/nrg.2017.69

    更新日期:2017-09-04
  • Settling the score: variant prioritization and Mendelian disease
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-14
    Karen Eilbeck, Aaron Quinlan, Mark Yandell

    When investigating Mendelian disease using exome or genome sequencing, distinguishing disease-causing genetic variants from the multitude of candidate variants is a complex, multidimensional task. Many prioritization tools and online interpretation resources exist, and professional organizations have offered clinical guidelines for review and return of prioritization results. In this Review, we describe the strengths and weaknesses of widely used computational approaches, explain their roles in the diagnostic and discovery process and discuss how they can inform (and misinform) expert reviewers. We place variant prioritization in the wider context of gene prioritization, burden testing and genotype–phenotype association, and we discuss opportunities and challenges introduced by whole-genome sequencing.

    更新日期:2017-09-04
  • Vertebrate sex determination: evolutionary plasticity of a fundamental switch
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-14
    Blanche Capel

    The discovery of the Sry gene in 1990 triggered a revolution in our understanding of sex determination. More recently, advances in non-model organisms have been fuelled by the rapid evolution of affordable genome and transcriptome technologies. This Review considers the unusual plasticity in the bipotential system of sex determination and some of the diverse mechanisms that have evolved to control this critical developmental decision, including strong genetic pathways, environmental influences and epigenetic regulation. Ideas emerging from model and non-model organisms that suggest that sex determination operates as an antagonistic network with the emergent property of bistability are discussed.

    更新日期:2017-09-04
  • Genome organization: Tracking chromosomal conformation through the cell cycle
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-24
    Carolina Perdigoto

    How chromosome organization changes during the cell cycle has been notoriously difficult to characterize owing to technical limitations, with most studies focusing on interphase nuclei. A new study reports single-cell genome conformation data for hundreds of cells in different phases of the cell cycle and

    更新日期:2017-08-17
  • Epigenetics: Getting instructions from mum
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-07
    Paulina Strzyz

    In gametes, most of the epigenetic modifications are erased before fertilization, but some epigenetic traits are retained and can be passed to the progeny in a process that remains poorly understood. Two studies now show that histone H3 Lys27 trimethylation (H3K27me3) is important for transgenerational

    更新日期:2017-08-17
  • Alternative splicing: A thermometer controlling gene expression
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-24
    Linda Koch

    To ensure a rapid response to environmental stress, the circadian clock — the endogenous oscillator that controls physiological and behavioural responses to the cycle of day and night — can be modulated by post-transcriptional mechanisms such as alternative splicing, instead of relying only on de

    更新日期:2017-08-17
  • Complex disease: From non-coding risk variant to biological mechanism in CAD
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-07
    Linda Koch

    Analyses of the genetic architecture of complex diseases such as coronary artery disease (CAD) have revealed that most genetic variants are located in non-coding regions of the genome. As regulatory variants can act over long genomic distances, the causal gene and specific mechanism through which

    更新日期:2017-08-17
  • TET-mediated active DNA demethylation: mechanism, function and beyond
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-05-30
    Xiaoji Wu, Yi Zhang

    In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation. Additionally, many regulatory mechanisms of this process have been identified. Technological advances in mapping and tracing the oxidized forms of 5mC allow further dissection of their functions. Furthermore, the biological functions of active DNA demethylation in various biological contexts have also been revealed. In this Review, we summarize the recent advances and highlight key unanswered questions.

    更新日期:2017-08-17
  • The impact of replication stress on replication dynamics and DNA damage in vertebrate cells
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-17
    Hervé Técher, Stéphane Koundrioukoff, Alain Nicolas, Michelle Debatisse

    The interplay between replication stress and the S phase checkpoint is a key determinant of genome maintenance, and has a major impact on human diseases, notably, tumour initiation and progression. Recent studies have yielded insights into sequence-dependent and sequence-independent sources of endogenous replication stress. These stresses result in nuclease-induced DNA damage, checkpoint activation and genome-wide replication fork slowing. Several hypotheses have been proposed to account for the mechanisms involved in this complex response. Recent results have shown that the slowing of the replication forks most commonly results from DNA precursor starvation. By concomitantly increasing the density of replication initiation, the cell elicits an efficient compensatory strategy to avoid mitotic anomalies and the inheritance of damage over cell generations.

    更新日期:2017-08-17
  • Network propagation: a universal amplifier of genetic associations
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-12
    Lenore Cowen, Trey Ideker, Benjamin J. Raphael, Roded Sharan

    Biological networks are powerful resources for the discovery of genes and genetic modules that drive disease. Fundamental to network analysis is the concept that genes underlying the same phenotype tend to interact; this principle can be used to combine and to amplify signals from individual genes. Recently, numerous bioinformatic techniques have been proposed for genetic analysis using networks, based on random walks, information diffusion and electrical resistance. These approaches have been applied successfully to identify disease genes, genetic modules and drug targets. In fact, all these approaches are variations of a unifying mathematical machinery — network propagation — suggesting that it is a powerful data transformation method of broad utility in genetic research.

    更新日期:2017-08-17
  • Exploiting induced and natural epigenetic variation for crop improvement
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-03
    Nathan M. Springer, Robert J. Schmitz

    Plant breeding has traditionally relied on combining the genetic diversity present within a species to develop combinations of alleles that provide desired traits. Epigenetic diversity may provide additional sources of variation within a species that could be captured or created for crop improvement. It will be important to understand the sources of epigenetic variation and the stability of newly formed epigenetic variants over generations to fully use the potential of epigenetic variation to improve crops. The development and application of methods for widespread epigenome profiling and engineering may generate new avenues for using the full potential of epigenetics in crop improvement.

    更新日期:2017-08-17
  • The interplay of epigenetic marks during stem cell differentiation and development
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-08-14
    Yaser Atlasi, Hendrik G. Stunnenberg

    Chromatin, the template for epigenetic regulation, is a highly dynamic entity that is constantly reshaped during early development and differentiation. Epigenetic modification of chromatin provides the necessary plasticity for cells to respond to environmental and positional cues, and enables the maintenance of acquired information without changing the DNA sequence. The mechanisms involve, among others, chemical modifications of chromatin, changes in chromatin constituents and reconfiguration of chromatin interactions and 3D structure. New advances in genome-wide technologies have paved the way towards an integrative view of epigenome dynamics during cell state transitions, and recent findings in embryonic stem cells highlight how the interplay between different epigenetic layers reshapes the transcriptional landscape.

    更新日期:2017-08-14
  • Gene expression: Microglia — environment defines identity
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-03
    Michelle Trenkmann

    Microglia are macrophage cells of the central nervous system (CNS) with crucial functions in neurodevelopment, immunity and tissue homeostasis, but this cell population has been notoriously difficult to study. A new study in Science describes the transcriptomic and epigenomic profiles of cortical microglia ex

    更新日期:2017-08-10
  • Disease genetics: Repeat expansion disorders — going through a phase
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-26
    Dorothy Clyde

    Some common inherited diseases are caused by nucleotide repeat expansions, whereby disease occurs only when the number of repeats exceeds a critical threshold. However, the underlying molecular mechanism linking repeat number to pathology has remained elusive. A recent study provides new insight by demonstrating that

    更新日期:2017-08-10
  • Non-coding RNA: A protective role for TERRA at telomeres
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-17
    Linda Koch

    From yeast to humans, telomeric DNA is transcribed by RNA polymerase II into the long non-coding (lnc) telomeric repeat-containing RNA (TERRA), but the exact functions of this RNA and its mode of action have remained poorly understood. Two studies in Cell now reveal a

    更新日期:2017-08-10
  • Technique: Sizing up tumours with Tuba-seq
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-12
    Michelle Trenkmann

    Precise determination of tumour growth is a prerequisite for estimating the functional importance of tumour suppressor alterations in cancer. A study in Nature Methods now describes the development of Tuba-seq, an approach that integrates tumour barcoding with high-throughput sequencing, to precisely quantify the size

    更新日期:2017-08-10
  • Cancer epigenetics: Therapy-induced transcription is cryptically widespread
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-26
    Darren J. Burgess

    The observations of abnormal epigenomes in cancer has motivated the pursuit of epigenome-targeted drugs for cancer therapy, but despite the clinical approval of various drugs, their cellular mechanisms of action are only partially understood. A new study demonstrates that DNA methyltransferase inhibitors (DNMTi) and histone

    更新日期:2017-08-10
  • Dynamic chromatin technologies: from individual molecules to epigenomic regulation in cells
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-05-22
    Olivier Cuvier, Beat Fierz

    The establishment and maintenance of chromatin states involves multiscale dynamic processes integrating transcription factor and multiprotein effector dynamics, cycles of chemical chromatin modifications, and chromatin structural organization. Recent developments in genomic technologies are emerging that are enabling a view beyond ensemble- and time-averaged properties and are revealing the importance of dynamic chromatin states for cell fate decisions, differentiation and reprogramming at the single-cell level. Concurrently, biochemical and single-molecule methodologies are providing key insights into the underlying molecular mechanisms. Combining results from defined in vitro and single-molecule studies with single-cell genomic approaches thus holds great promise for understanding chromatin-based transcriptional memory and cell fate. In this Review, we discuss recent developments in biochemical, single-molecule biophysical and single-cell genomic technologies and review how the findings from these approaches can be integrated to paint a comprehensive picture of dynamic chromatin states.

    更新日期:2017-08-10
  • Cancer genetics: A 3D view of genome rearrangements
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-03
    Linda Koch

    Somatic structural genome alterations such as changes in copy number or chromosomal rearrangements can promote genome instability and cancer development, and identification of these mutations is crucial to diagnose cancer early and provide targeted therapies. Now, Harewood et al. report the use of Hi-C

    更新日期:2017-08-10
  • Reference standards for next-generation sequencing
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-19
    Simon A. Hardwick, Ira W. Deveson, Tim R. Mercer

    Next-generation sequencing (NGS) provides a broad investigation of the genome, and it is being readily applied for the diagnosis of disease-associated genetic features. However, the interpretation of NGS data remains challenging owing to the size and complexity of the genome and the technical errors that are introduced during sample preparation, sequencing and analysis. These errors can be understood and mitigated through the use of reference standards — well-characterized genetic materials or synthetic spike-in controls that help to calibrate NGS measurements and to evaluate diagnostic performance. The informed use of reference standards, and associated statistical principles, ensures rigorous analysis of NGS data and is essential for its future clinical use.

    更新日期:2017-08-10
  • Human Y-chromosome variation in the genome-sequencing era
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-05-30
    Mark A. Jobling, Chris Tyler-Smith

    The properties of the human Y chromosome – namely, male specificity, haploidy and escape from crossing over — make it an unusual component of the genome, and have led to its genetic variation becoming a key part of studies of human evolution, population history, genealogy, forensics and male medical genetics. Next-generation sequencing (NGS) technologies have driven recent progress in these areas. In particular, NGS has yielded direct estimates of mutation rates, and an unbiased and calibrated molecular phylogeny that has unprecedented detail. Moreover, the availability of direct-to-consumer NGS services is fuelling a rise of 'citizen scientists', whose interest in resequencing their own Y chromosomes is generating a wealth of new data.

    更新日期:2017-08-10
  • The origin of Metazoa: a unicellular perspective
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-05-08
    Arnau Sebé-Pedrós, Bernard M. Degnan, Iñaki Ruiz-Trillo

    The first animals evolved from an unknown single-celled ancestor in the Precambrian period. Recently, the identification and characterization of the genomic and cellular traits of the protists most closely related to animals have shed light on the origin of animals. Comparisons of animals with these unicellular relatives allow us to reconstruct the first evolutionary steps towards animal multicellularity. Here, we review the results of these investigations and discuss their implications for understanding the earliest stages of animal evolution, including the origin of metazoan genes and genome function.

    更新日期:2017-08-10
  • Dissecting evolution and disease using comparative vertebrate genomics
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-24
    Jennifer R. S. Meadows, Kerstin Lindblad-Toh

    With the generation of more than 100 sequenced vertebrate genomes in less than 25 years, the key question arises of how these resources can be used to inform new or ongoing projects. In the past, this diverse collection of sequences from human as well as model and non-model organisms has been used to annotate the human genome and to increase the understanding of human disease. In the future, comparative vertebrate genomics in conjunction with additional genomic resources will yield insights into the processes of genome function, evolution, speciation, selection and adaptation, as well as the quantification of species diversity. In this Review, we discuss how the genomics of non-human organisms can provide insights into vertebrate biology and how this can contribute to the understanding of human physiology and health.

    更新日期:2017-08-10
  • Evolutionary biology through the lens of budding yeast comparative genomics
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-17
    Souhir Marsit, Jean-Baptiste Leducq, Éléonore Durand, Axelle Marchant, Marie Filteau, Christian R. Landry

    The budding yeast Saccharomyces cerevisiae is a highly advanced model system for studying genetics, cell biology and systems biology. Over the past decade, the application of high-throughput sequencing technologies to this species has contributed to this yeast also becoming an important model for evolutionary genomics. Indeed, comparative genomic analyses of laboratory, wild and domesticated yeast populations are providing unprecedented detail about many of the processes that govern evolution, including long-term processes, such as reproductive isolation and speciation, and short-term processes, such as adaptation to natural and domestication-related environments.

    更新日期:2017-08-10
  • The impact of replication stress on replication dynamics and DNA damage in vertebrate cells
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-17
    Hervé Técher, Stéphane Koundrioukoff, Alain Nicolas, Michelle Debatisse

    The interplay between replication stress and the S phase checkpoint is a key determinant of genome maintenance, and has a major impact on human diseases, notably, tumour initiation and progression. Recent studies have yielded insights into sequence-dependent and sequence-independent sources of endogenous replication stress. These stresses result in nuclease-induced DNA damage, checkpoint activation and genome-wide replication fork slowing. Several hypotheses have been proposed to account for the mechanisms involved in this complex response. Recent results have shown that the slowing of the replication forks most commonly results from DNA precursor starvation. By concomitantly increasing the density of replication initiation, the cell elicits an efficient compensatory strategy to avoid mitotic anomalies and the inheritance of damage over cell generations.

    更新日期:2017-08-10
  • Exploiting induced and natural epigenetic variation for crop improvement
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-07-03
    Nathan M. Springer, Robert J. Schmitz

    Plant breeding has traditionally relied on combining the genetic diversity present within a species to develop combinations of alleles that provide desired traits. Epigenetic diversity may provide additional sources of variation within a species that could be captured or created for crop improvement. It will be important to understand the sources of epigenetic variation and the stability of newly formed epigenetic variants over generations to fully use the potential of epigenetic variation to improve crops. The development and application of methods for widespread epigenome profiling and engineering may generate new avenues for using the full potential of epigenetics in crop improvement.

    更新日期:2017-08-10
  • Synthetic lethality and cancer
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-26
    Nigel J. O'Neil, Melanie L. Bailey, Philip Hieter

    A synthetic lethal interaction occurs between two genes when the perturbation of either gene alone is viable but the perturbation of both genes simultaneously results in the loss of viability. Key to exploiting synthetic lethality in cancer treatment are the identification and the mechanistic characterization of robust synthetic lethal genetic interactions. Advances in next-generation sequencing technologies are enabling the identification of hundreds of tumour-specific mutations and alterations in gene expression that could be targeted by a synthetic lethality approach. The translation of synthetic lethality to therapy will be assisted by the synthesis of genetic interaction data from model organisms, tumour genomes and human cell lines.

    更新日期:2017-08-10
  • Network propagation: a universal amplifier of genetic associations
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-06-12
    Lenore Cowen, Trey Ideker, Benjamin J. Raphael, Roded Sharan

    Biological networks are powerful resources for the discovery of genes and genetic modules that drive disease. Fundamental to network analysis is the concept that genes underlying the same phenotype tend to interact; this principle can be used to combine and to amplify signals from individual genes. Recently, numerous bioinformatic techniques have been proposed for genetic analysis using networks, based on random walks, information diffusion and electrical resistance. These approaches have been applied successfully to identify disease genes, genetic modules and drug targets. In fact, all these approaches are variations of a unifying mathematical machinery — network propagation — suggesting that it is a powerful data transformation method of broad utility in genetic research.

    更新日期:2017-08-10
  • TET-mediated active DNA demethylation: mechanism, function and beyond
    Nat. Rev. Genet. (IF 40.282) Pub Date : 2017-05-30
    Xiaoji Wu, Yi Zhang

    In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation. Additionally, many regulatory mechanisms of this process have been identified. Technological advances in mapping and tracing the oxidized forms of 5mC allow further dissection of their functions. Furthermore, the biological functions of active DNA demethylation in various biological contexts have also been revealed. In this Review, we summarize the recent advances and highlight key unanswered questions.

    更新日期:2017-08-10
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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