Nature Reviews Genetics

Evo-Devo: Flowering form.

Publication Date: 2013 May 21 PMID: 23689902
Authors: Muers, M.
Journal: Nat Rev Genet

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Mechanisms and models of somatic cell reprogramming.

Publication Date: 2013 Jun PMID: 23681063
Authors: Buganim, Y. - Faddah, D. A. - Jaenisch, R.
Journal: Nat Rev Genet

Conversion of somatic cells to pluripotency by defined factors is a long and complex process that yields embryonic-stem-cell-like cells that vary in their developmental potential. To improve the quality of resulting induced pluripotent stem cells (iPSCs), which is important for potential therapeutic applications, and to address fundamental questions about control of cell identity, molecular mechanisms of the reprogramming process must be understood. Here we discuss recent discoveries regarding the role of reprogramming factors in remodelling the genome, including new insights into the function of MYC, and describe the different phases, markers and emerging models of reprogramming.

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Molecular genetic testing and the future of clinical genomics.

Publication Date: 2013 Jun PMID: 23681062
Authors: Katsanis, S. H. - Katsanis, N.
Journal: Nat Rev Genet

Genomic technologies are reaching the point of being able to detect genetic variation in patients at high accuracy and reduced cost, offering the promise of fundamentally altering medicine. Still, although scientists and policy advisers grapple with how to interpret and how to handle the onslaught and ambiguity of genome-wide data, established and well-validated molecular technologies continue to have an important role, especially in regions of the world that have more limited access to next-generation sequencing capabilities. Here we review the range of methods currently available in a clinical setting as well as emerging approaches in clinical molecular diagnostics. In parallel, we outline implementation challenges that will be necessary to address to ensure the future of genetic medicine.

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Non-coding RNA: R-loop stability controls expression.

Publication Date: 2013 Jun PMID: 23669759
Authors: Muers, M.
Journal: Nat Rev Genet

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Epigenetics: BPA and imprinting disruption.

Publication Date: 2013 Jun PMID: 23669758
Authors: Burgess, D. J.
Journal: Nat Rev Genet

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Gene regulation: Determining global and specific regulation.

Publication Date: 2013 Jun PMID: 23669757
Authors: Muers, M.
Journal: Nat Rev Genet

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Stem cells: Nuclear departure controls pluripotency exit.

Publication Date: 2013 Jun PMID: 23669756
Authors: Burgess, D. J.
Journal: Nat Rev Genet

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Epigenetics: Genome-wide views of methylation readers.

Publication Date: 2013 Jun PMID: 23669755
Authors: Flintoft, L.
Journal: Nat Rev Genet

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Disease genetics: Improving GWASs with secondary phenotypes.

Publication Date: 2013 Jun PMID: 23669754
Authors: Stower, H.
Journal: Nat Rev Genet

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Transcriptomics: Isoform diversity revealed.

Publication Date: 2013 Jun PMID: 23669753
Authors: Flintoft, L.
Journal: Nat Rev Genet

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Development: Testing the threshold-dependent model.

Publication Date: 2013 Jun PMID: 23669752
Authors: Stower, H.
Journal: Nat Rev Genet

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Eric olson.

Publication Date: 2013 Jun PMID: 23657483
Authors:
Journal: Nat Rev Genet

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Population genetics: Mobile elements across human populations.

Publication Date: 2013 Jun PMID: 23657482
Authors: Burgess, D. J.
Journal: Nat Rev Genet

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Meta-analysis methods for genome-wide association studies and beyond.

Publication Date: 2013 Jun PMID: 23657481
Authors: Evangelou, E. - Ioannidis, J. P.
Journal: Nat Rev Genet

Meta-analysis of genome-wide association studies (GWASs) has become a popular method for discovering genetic risk variants. Here, we overview both widely applied and newer statistical methods for GWAS meta-analysis, including issues of interpretation and assessment of sources of heterogeneity. We also discuss extensions of these meta-analysis methods to complex data. Where possible, we provide guidelines for researchers who are planning to use these methods. Furthermore, we address special issues that may arise for meta-analysis of sequencing data and rare variants. Finally, we discuss challenges and solutions surrounding the goals of making meta-analysis data publicly available and building powerful consortia.

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Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data.

Publication Date: 2013 Jun PMID: 23657480
Authors: Dekker, J. - Marti-Renom, M. A. - Mirny, L. A.
Journal: Nat Rev Genet

How DNA is organized in three dimensions inside the cell nucleus and how this affects the ways in which cells access, read and interpret genetic information are among the longest standing questions in cell biology. Using newly developed molecular, genomic and computational approaches based on the chromosome conformation capture technology (such as 3C, 4C, 5C and Hi-C), the spatial organization of genomes is being explored at unprecedented resolution. Interpreting the increasingly large chromatin interaction data sets is now posing novel challenges. Here we describe several types of statistical and computational approaches that have recently been developed to analyse chromatin interaction data.

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Understanding the origin of species with genome-scale data: modelling gene flow.

Publication Date: 2013 Jun PMID: 23657479
Authors: Sousa, V. - Hey, J.
Journal: Nat Rev Genet

As it becomes easier to sequence multiple genomes from closely related species, evolutionary biologists working on speciation are struggling to get the most out of very large population genomic data sets. Such data hold the potential to resolve long-standing questions in evolutionary biology about the role of gene exchange in species formation. In principle, the new population genomic data can be used to disentangle the conflicting roles of natural selection and gene flow during the divergence process. However, there are great challenges in taking full advantage of such data, especially with regard to including recombination in genetic models of the divergence process. Current data, models, methods and the potential pitfalls in using them will be considered here.

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Epigenetics: Legionella makes its mark on histones.

Publication Date: 2013 Jun PMID: 23657478
Authors: Kahrstrom, C. T.
Journal: Nat Rev Genet

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Population genomics: Noah's Ark arrives.

Publication Date: 2013 Jun PMID: 23629550
Authors: Flintoft, L.
Journal: Nat Rev Genet

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Genomics: New zebrafish genome resources.

Publication Date: 2013 Jun PMID: 23629549
Authors: Burgess, D. J.
Journal: Nat Rev Genet

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Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches.

Publication Date: 2013 Jun PMID: 23609411
Authors: Fairclough, R. J. - Wood, M. J. - Davies, K. E.
Journal: Nat Rev Genet

Duchenne muscular dystrophy (DMD) is a devastating progressive disease for which there is currently no effective treatment except palliative therapy. There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene. The lessons learned from these approaches will be applicable to many other disorders.

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Gene expression: Super enhancers.

Publication Date: 2013 Jun PMID: 23609410
Authors: Stower, H.
Journal: Nat Rev Genet

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Computational solutions for omics data.

Publication Date: 2013 May PMID: 23594911
Authors: Berger, B. - Peng, J. - Singh, M.
Journal: Nat Rev Genet

High-throughput experimental technologies are generating increasingly massive and complex genomic data sets. The sheer enormity and heterogeneity of these data threaten to make the arising problems computationally infeasible. Fortunately, powerful algorithmic techniques lead to software that can answer important biomedical questions in practice. In this Review, we sample the algorithmic landscape, focusing on state-of-the-art techniques, the understanding of which will aid the bench biologist in analysing omics data. We spotlight specific examples that have facilitated and enriched analyses of sequence, transcriptomic and network data sets.

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Cancer genome-sequencing study design.

Publication Date: 2013 May PMID: 23594910
Authors: Mwenifumbo, J. C. - Marra, M. A.
Journal: Nat Rev Genet

Discoveries from cancer genome sequencing have the potential to translate into advances in cancer prevention, diagnostics, prognostics, treatment and basic biology. Given the diversity of downstream applications, cancer genome-sequencing studies need to be designed to best fulfil specific aims. Knowledge of second-generation cancer genome-sequencing study design also facilitates assessment of the validity and importance of the rapidly growing number of published studies. In this Review, we focus on the practical application of second-generation sequencing technology (also known as next-generation sequencing) to cancer genomics and discuss how aspects of study design and methodological considerations - such as the size and composition of the discovery cohort - can be tailored to serve specific research aims.

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A genomic view of mosaicism and human disease.

Publication Date: 2013 May PMID: 23594909
Authors: Biesecker, L. G. - Spinner, N. B.
Journal: Nat Rev Genet

Genomic technologies, including next-generation sequencing (NGS) and single-nucleotide polymorphism (SNP) microarrays, have provided unprecedented opportunities to assess genomic variation among, and increasingly within, individuals. It has long been known that cancer is a mosaic genetic disorder, but mosaicism is now apparent in a diverse range of other clinical disorders, as indicated by their tissue distributions and inheritance patterns. Recent technical advances have uncovered the causative mosaic variant underlying many of these conditions and have provided insight into the pervasiveness of mosaicism in normal individuals. Here, we discuss the clinical and molecular classes of mosaicism, their detection and the biological insights gained from these studies.

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DNA damage: A damaging neuronal activity.

Publication Date: 2013 May PMID: 23594908
Authors: Burgess, D. J.
Journal: Nat Rev Genet

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Genome evolution: Complex fitness effects of ploidy states.

Publication Date: 2013 May PMID: 23594907
Authors: Burgess, D. J.
Journal: Nat Rev Genet

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Gene regulation: Circadian control in chloroplasts.

Publication Date: 2013 May PMID: 23594906
Authors: Muers, M.
Journal: Nat Rev Genet

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Technology: High-throughput protein interactions.

Publication Date: 2013 May PMID: 23594905
Authors: Muers, M.
Journal: Nat Rev Genet

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Non-coding RNA: Non-coding RNA changes enzyme specificity.

Publication Date: 2013 May PMID: 23594904
Authors: Flintoft, L.
Journal: Nat Rev Genet

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Population genomics: Characterizing indels.

Publication Date: 2013 May PMID: 23594903
Authors: Stower, H.
Journal: Nat Rev Genet

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Cancer genetics: Focus on susceptibility to hormone-related cancers.

Publication Date: 2013 May PMID: 23594902
Authors: Flintoft, L.
Journal: Nat Rev Genet

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DNA methylation: Placental partially methylated domains.

Publication Date: 2013 May PMID: 23594901
Authors: Stower, H.
Journal: Nat Rev Genet

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Pathogen sequencing: Picking and choosing.

Publication Date: 2013 May PMID: 23568487
Authors: Stower, H.
Journal: Nat Rev Genet

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From neural development to cognition: unexpected roles for chromatin.

Publication Date: 2013 May PMID: 23568486
Authors: Ronan, J. L. - Wu, W. - Crabtree, G. R.
Journal: Nat Rev Genet

Recent genome-sequencing studies in human neurodevelopmental and psychiatric disorders have uncovered mutations in many chromatin regulators. These human genetic studies, along with studies in model organisms, are providing insight into chromatin regulatory mechanisms in neural development and how alterations to these mechanisms can cause cognitive deficits, such as intellectual disability. We discuss several implicated chromatin regulators, including BAF (also known as SWI/SNF) and CHD8 chromatin remodellers, HDAC4 and the Polycomb component EZH2. Interestingly, mutations in EZH2 and certain BAF complex components have roles in both neurodevelopmental disorders and cancer, and overlapping point mutations are suggesting functionally important residues and domains. We speculate on the contribution of these similar mutations to disparate disorders.

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Functional and evolutionary implications of gene orthology.

Publication Date: 2013 May PMID: 23552219
Authors: Gabaldon, T. - Koonin, E. V.
Journal: Nat Rev Genet

Orthologues and paralogues are types of homologous genes that are related by speciation or duplication, respectively. Orthologous genes are generally assumed to retain equivalent functions in different organisms and to share other key properties. Several recent comparative genomic studies have focused on testing these expectations. Here we discuss the complexity of the evolution of gene-phenotype relationships and assess the validity of the key implications of orthology and paralogy relationships as general statistical trends and guiding principles.

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Small RNAs: Defining piRNA expression.

Publication Date: 2013 May PMID: 23552218
Authors: Burgess, D. J.
Journal: Nat Rev Genet

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Gene expression: Extra X expression.

Publication Date: 2013 May PMID: 23552217
Authors: Stower, H.
Journal: Nat Rev Genet

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Gene regulation: In charge of translation.

Publication Date: 2013 May PMID: 23552216
Authors: Flintoft, L.
Journal: Nat Rev Genet

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DNA repair: Search space.

Publication Date: 2013 May PMID: 23552215
Authors: Muers, M.
Journal: Nat Rev Genet

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Evolution: Replication-transcription conflict promotes gene evolution.

Publication Date: 2013 May PMID: 23552214
Authors: Domingues, V.
Journal: Nat Rev Genet

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Synthetic biology: Quality and quantity.

Publication Date: 2013 May PMID: 23529070
Authors: Muers, M.
Journal: Nat Rev Genet

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