Hot off the presses! Jul 01 Nat Rev Gen

The Jul 01 issue of the Nat Rev Gen is now up on Pubget (About Nat Rev Gen): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Gen 12(7):453 (2011)
  
• Chromatin: Positioning the players | PDF (224 KB)
  - Nat Rev Gen 12(7):454 (2011)
  Recent applications of high-throughput sequencing to provide genome-scale maps of nucleosome positioning have greatly increased our understanding of how the chromatin landscape relates to genomic features such as transcription start sites (TSSs) and regulatory elements. However, there are many unresolved questions about what determines nucleosome organization.
• Network biology: Dosage adds new dimension | PDF (611 KB)
  - Nat Rev Gen 12(7):455 (2011)
  A new study takes us a step closer to mapping the functional wiring diagram of Saccharomyces cerevisiae. The authors have identified an unexplored portion of the cell's global network by generating a map of dosage-suppression interactions, which are connections between conditional query genes and other genes that, when overexpressed, rescue the mutant phenotype.
• Evolution | Computational biology | MicroRNA | Epigenetics | PDF (80 KB)
  - Nat Rev Gen 12(7):455 (2011)
  Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme Hayden, E. J., Ferrada, E. & Wagner, A.Nature 474, 92–95 (2011)
• Complex disease: Ups and downs at the MHC | PDF (243 KB)
  - Nat Rev Gen 12(7):456 (2011)
  The human major histocompatibility complex (MHC) is an unusual part of the genome. This ~3.5 Mb region has the highest density of genes in the human genome (the majority of which have fundamental roles in immunity), as well as high levels of variation and extensive linkage disequilibrium.
• Disease genetics: Converging models for autism | PDF (434 KB)
  - Nat Rev Gen 12(7):456 (2011)
  Two approaches to dissect the molecular genetic basis of autism have improved our understanding of the developmental processes and functional interactions involved in this heterogeneous condition. One paper reports dysregulation of transcription and splicing in autistic brains, and another describes an interactome of autism-associated proteins that points to there being common mechanisms underlying different autistic phenotypes.
• Development | Stem cells | Chromatin | Complex traits | PDF (80 KB)
  - Nat Rev Gen 12(7):456 (2011)
  Initiation of proximal-distal patterning in the vertebrate limb by signals and growth Cooper, K. L.et al. Science 332, 1083–1086 (2011)
• Unexpected mismatches, but dogma intact | PDF (79 KB)
  - Nat Rev Gen 12(7):457 (2011)
  A debate has been stirred by a report from Vivian Cheung's laboratory published in Science (19 May 2011; doi:10.1126/science.1207018). The authors demonstrated unprecedented mismatches between RNA sequences and the DNA that encodes them, as identified by next-generation sequencing.
• David Page | PDF (124 KB)
  - Nat Rev Gen 12(7):458 (2011)
  The 2011 March of Dimes Prize in Developmental Biology has been jointly awarded to Patricia Jacobs, of Southampton University Medical School and the Wessex Regional Genetics Laboratory, and to David Page, of the Whitehead Institute, Massachusetts Institute of Technology and Howard Hughes Medical Institute, for their pioneering research on the X and Y chromosomes. The prize recognizes researchers whose work has contributed to our understanding of the science that underlies birth defects.
• Transcription by RNA polymerase III: more complex than we thought
  - Nat Rev Gen 12(7):459 (2011)
  RNA polymerase (Pol) III is highly specialized for the production of short non-coding RNAs. Once considered to be under relatively simple controls, recent studies using chromatin immunoprecipitation followed by sequencing (ChIP–seq) have revealed unexpected levels of complexity for Pol III regulation, including substantial cell-type selectivity and intriguing overlap with Pol II transcription. Here I describe these novel insights and consider their implications and the questions that remain.
• Family-based designs for genome-wide association studies
  - Nat Rev Gen 12(7):465 (2011)
  Association mapping has successfully identified common SNPs associated with many diseases. However, the inability of this class of variation to account for most of the supposed heritability has led to a renewed interest in methods — primarily linkage analysis — to detect rare variants. Family designs allow for control of population stratification, investigations of questions such as parent-of-origin effects and other applications that are imperfectly or not readily addressed in case–control association studies. This article guides readers through the interface between linkage and association analysis, reviews the new methodologies and provides useful guidelines for applications. Just as effective SNP-genotyping tools helped to realize the potential of association studies, next-generation sequencing tools will benefit genetic studies by improving the power of family-based approaches.
• Beyond DNA: integrating inclusive inheritance into an extended theory of evolution
  - Nat Rev Gen 12(7):475 (2011)
  Many biologists are calling for an 'extended evolutionary synthesis' that would 'modernize the modern synthesis' of evolution. Biological information is typically considered as being transmitted across generations by the DNA sequence alone, but accumulating evidence indicates that both genetic and non-genetic inheritance, and the interactions between them, have important effects on evolutionary outcomes. We review the evidence for such effects of epigenetic, ecological and cultural inheritance and parental effects, and outline methods that quantify the relative contributions of genetic and non-genetic heritability to the transmission of phenotypic variation across generations. These issues have implications for diverse areas, from the question of missing heritability in human complex-trait genetics to the basis of major evolutionary transitions.
• Towards systematic functional characterization of cancer genomes
  - Nat Rev Gen 12(7):487 (2011)
  Whole-genome approaches to identify genetic and epigenetic alterations in cancer genomes have begun to provide new insights into the range of molecular events that occurs in human tumours. Although in some cases this knowledge immediately illuminates a path towards diagnostic or therapeutic implementation, the bewildering lists of mutations in each tumour make it clear that systematic functional approaches are also necessary to obtain a comprehensive molecular understanding of cancer. Here we review the current range of methods, assays and approaches for genome-scale interrogation of gene function in cancer. We also discuss the integration of functional-genomics approaches with the outputs from cancer genome sequencing efforts.
• Genome-wide genetic marker discovery and genotyping using next-generation sequencing
  - Nat Rev Gen 12(7):499 (2011)
  The advent of next-generation sequencing (NGS) has revolutionized genomic and transcriptomic approaches to biology. These new sequencing tools are also valuable for the discovery, validation and assessment of genetic markers in populations. Here we review and discuss best practices for several NGS methods for genome-wide genetic marker development and genotyping that use restriction enzyme digestion of target genomes to reduce the complexity of the target. These new methods — which include reduced-representation sequencing using reduced-representation libraries (RRLs) or complexity reduction of polymorphic sequences (CRoPS), restriction-site-associated DNA sequencing (RAD-seq) and low coverage genotyping — are applicable to both model organisms with high-quality reference genome sequences and, excitingly, to non-model species with no existing genomic data.
• The future of direct-to-consumer clinical genetic tests
  - Nat Rev Gen 12(7):511 (2011)
  In light of the meeting of the US Food and Drug Administration (FDA) in March 2011 to discuss the regulation of clinical direct-to-consumer (DTC) genetic tests, we have invited five experts to consider the best means of overseeing the ordering and interpretation of these tests. Should these tests be regulated? If so, who, if anyone, should communicate results to consumers?
• Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
  - Nat Rev Gen 12(7):515 (2011)
  In the above article, information on clinical trials using adeno-associated virus (AAV) vectors for the treatment of Leber's congenital amaurosis was omitted from table 1. The corrected table is available at http://www.nature.com/nrg/journal/v12/n5/full/nrg2988.html. The authors apologize for this omission.