Hot off the presses! Jan 01 Nat Rev Genet

The Jan 01 issue of the Nat Rev Genet is now up on Pubget (About Nat Rev Genet): 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 Genet 12(1):1 (2011)
  
• Dosage compensation: What dosage compensation? | PDF (198 KB)
  - Nat Rev Genet 12(1):2 (2011)
  According to a widely held view first proposed by Susumu Ohno, genes on the active mammalian X chromosome are expressed at twice the level of those present on two autosomes. A study using RNA–seq data overturns this model by showing that, in mice and humans, genes on the X chromosome are expressed at the same level as those on autosomes.
• Gene Expression: One size does not fit all for transcriptomes | PDF (209 KB)
  - Nat Rev Genet 12(1):3 (2011)
  Cells of a particular cell type, in both multicellular and unicellular organisms, are remarkably uniform in size. This indicates that cell size is not just sensed but tightly regulated, yet little is currently known about the causes and consequences of changes in cell size.
• Stem cells | Development | Small RNAs | Gene regulation | PDF (116 KB)
  - Nat Rev Genet 12(1):3 (2011)
  Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells Loewer, S.et al. Nature Genet. 42, 1113–1117 (2010)
• Gene Regulation: Noise versus plasticity | PDF (209 KB)
  - Nat Rev Genet 12(1):4 (2011)
  The variation in the expression level of a gene in response to stimuli (gene expression 'plasticity') often correlates with the variability in the expression level of that gene among cells under the same conditions (gene expression 'noise'). But are plasticity and noise intrinsically linked?
• Synthetic biology: RNA device rewires cellular networks | PDF (247 KB)
  - Nat Rev Genet 12(1):4 (2011)
  Synthetic devices that translate molecular inputs into gene expression changes are valuable for manipulating cellular behaviour, but until now these circuits have only been able to respond to a limited set of inputs, such as transcription factors. However, a new synthetic device based on RNA can respond sensitively to alterations in the levels of endogenous signalling molecules, and so can potentially link disease-associated pathways to cell fate decisions.
• Gene Therapy: MicroRNAs provide powerful postponement | PDF (252 KB)
  - Nat Rev Genet 12(1):4 (2011)
  For successful clinical application, retroviral gene therapy must overcome many technical challenges, one of which is the appropriate regulation of transgenes. A recent study describes a sophisticated new technique for the developmental regulation of a therapeutic transgene using engineered binding sites for microRNAs (miRNAs).
• Genome biology | Gene expression | Cancer genomics | DNA forensics | PDF (121 KB)
  - Nat Rev Genet 12(1):5 (2011)
  Genome-wide characterization of centromeric satellites from multiple mammalian genomes Alkan, C.et al. Genome Res.16 Nov 2010 (doi:10.1101/gr.111278.110)
• Epigenetics: Methylation from mother | PDF (210 KB)
  - Nat Rev Genet 12(1):6 (2011)
  There is increasing interest in discovering what epigenetic information is passed from parent to offspring and how it influences development. Two studies of mouse embryogenesis now show that transmission of DNA methylation from gametes is predominantly maternal.
• Technology: Making more genes, better and for less | PDF (168 KB)
  - Nat Rev Genet 12(1):6 (2011)
  Methods for large-scale, high-quality gene synthesis at an affordable price are needed for advances in both synthetic biology and biotechnology. Two recent studies, both led by the group of George Church, describe new approaches to DNA synthesis that provide steps towards this goal.
• Charting histone modifications and the functional organization of mammalian genomes
  - Nat Rev Genet 12(1):7 (2011)
  A succession of technological advances over the past decade have enabled researchers to chart maps of histone modifications and related chromatin structures with increasing accuracy, comprehensiveness and throughput. The resulting data sets highlight the interplay between chromatin and genome function, dynamic variations in chromatin structure across cellular conditions, and emerging roles for large-scale domains and higher-ordered chromatin organization. Here we review a selection of recent studies that have probed histone modifications and successive layers of chromatin structure in mammalian genomes, the patterns that have been identified and future directions for research.
• Small RNA sorting: matchmaking for Argonautes
  - Nat Rev Genet 12(1):19 (2011)
  Small RNAs directly or indirectly impact nearly every biological process in eukaryotic cells. To perform their myriad roles, not only must precise small RNA species be generated, but they must also be loaded into specific effector complexes called RNA-induced silencing complexes (RISCs). Argonaute proteins form the core of RISCs and different members of this large family have specific expression patterns, protein binding partners and biochemical capabilities. In this Review, we explore the mechanisms that pair specific small RNA strands with their partner proteins, with an eye towards the substantial progress that has been recently made in understanding the sorting of the major small RNA classes — microRNAs (miRNAs) and small interfering RNAs (siRNAs) — in plants and animals.
• Synonymous but not the same: the causes and consequences of codon bias
  - Nat Rev Genet 12(1):32 (2011)
  Despite their name, synonymous mutations have significant consequences for cellular processes in all taxa. As a result, an understanding of codon bias is central to fields as diverse as molecular evolution and biotechnology. Although recent advances in sequencing and synthetic biology have helped to resolve longstanding questions about codon bias, they have also uncovered striking patterns that suggest new hypotheses about protein synthesis. Ongoing work to quantify the dynamics of initiation and elongation is as important for understanding natural synonymous variation as it is for designing transgenes in applied contexts.
• Boundary formation and maintenance in tissue development
  - Nat Rev Genet 12(1):43 (2011)
  The formation and maintenance of boundaries between neighbouring groups of embryonic cells is vital for development because groups of cells with distinct functions must often be kept physically separated. Furthermore, because cells at the boundary often take on important signalling functions by acting as organizing centres, boundary shape and integrity can also control the outcome of many downstream patterning events. Recent experimental findings and theoretical descriptions have shed new light on classic questions about boundaries. In particular, in the past couple of years the role of forces acting in epithelial tissues to maintain boundaries has emerged as a new principle in understanding how early pattern is made into permanent anatomy.
• Network medicine: a network-based approach to human disease
  - Nat Rev Genet 12(1):56 (2011)
  Given the functional interdependencies between the molecular components in a human cell, a disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex intracellular and intercellular network that links tissue and organ systems. The emerging tools of network medicine offer a platform to explore systematically not only the molecular complexity of a particular disease, leading to the identification of disease modules and pathways, but also the molecular relationships among apparently distinct (patho)phenotypes. Advances in this direction are essential for identifying new disease genes, for uncovering the biological significance of disease-associated mutations identified by genome-wide association studies and full-genome sequencing, and for identifying drug targets and biomarkers for complex diseases.
• Pharmacogenomics: will the promise be fulfilled?
  - Nat Rev Genet 12(1):69 (2011)
  Tools such as genome resequencing and genome-wide association studies have recently been used to uncover a number of variants that affect drug toxicity and efficacy, as well as potential drug targets. But how much closer are we to incorporating pharmacogenomics into routine clinical practice? Five experts discuss how far we have come, and highlight the technological, informatics, educational and practical obstacles that stand in the way of realizing genome-driven medicine.
• Correspondence: Statistical interaction in human genetics: how should we model it if we are looking for biological interaction?
  - Nat Rev Genet 12(1):74 (2011)
  In her Review article (Detecting gene–gene interactions that underlie human diseases. Nature Rev. Genet.10, 392–404 (2009)
• Measuring selection in contemporary human populations
  - Nat Rev Genet 12(1):74 (2011)
  In Box 3 of the above article, two equations were given incorrectly. In the second column of the table, last row, the correct equation is: (Ï€1 × F1 × p1 + (1 − Ï€1) × p2 × F2)/F − Ï€1 where F is the fertility rate for the total population. In the third column, last row, the line should begin with a lower case g, to indicate simple covariance, and not G, which indicates the matrix. The correct equation should read: g × Cov(F,SBP)/Var(SBP1) = h2 × Cov(F,SBP) = g × b