Hot off the presses! Mar 01 Nat Rev Genet

The Mar 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(3):151 (2011)
  
• Gene expression: Teasing out transcription | PDF (220 KB)
  - Nat Rev Genet 12(3):152 (2011)
  The discovery a few years ago that transcription can initiate in a bidirectional manner, with many antisense transcripts being quickly degraded, opened our eyes to the extent to which transcriptional control is exerted after initiation. So far, analysis of this has been limited owing to the difficulty of detecting nascent transcripts in vivo.
• Stem cells: Scorecards for pluripotent cell lines | PDF (161 KB)
  - Nat Rev Genet 12(3):153 (2011)
  There is much debate over the extent of differences between human induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) and the differences among cell lines of each type. A scoring system based on quantitative and functional characterization of iPSC and ESC lines now provides a practical approach to evaluate cell lines.
• Complex disease: Finding functions in the wilderness | PDF (179 KB)
  - Nat Rev Genet 12(3):153 (2011)
  Most disease-associated variants that are identified in genome-wide association (GWA) studies fall within non-coding regions of the genome — much to the investigators' frustration, for it is often far from obvious how to follow up on these associations at the molecular level. A new study describes how this challenge was met for a small genomic region, 9p21, that had previously been associated with cardiovascular phenotypes and type 2 diabetes.
• Gene regulation: Grouped in silence | PDF (163 KB)
  - Nat Rev Genet 12(3):154 (2011)
  .Nuclear subdomains that contain Polycomb group (PcG) bodies are known to silence gene activity — but do they do so directly, by binding of PcG proteins to target promoters, or indirectly, by compartmentalizing the target genes into the repressive subdomain?
• Evo-devo: Doing the time warp | PDF (211 KB)
  - Nat Rev Genet 12(3):154 (2011)
  Evolutionary developmental biology is being revolutionized by increasingly extensive and detailed gene expression data for a growing range of species. A recent study demonstrates a new way of investigating evolutionary novelties by looking for clusters of genes that are expressed differently between fruitflies and mosquitoes at particular times during development.
• Cancer genetics: Initially complex, always heterogeneous | PDF (221 KB)
  - Nat Rev Genet 12(3):154 (2011)
  The genetic complexity and heterogeneity of cancer is becoming increasingly appreciated through genomic and histological analyses. Two recent studies add further weight to this concept, revealing that even the subpopulation of leukaemia-initiating cells in individual patient samples can have surprising genetic heterogeneity.
• Transcriptomics | Disease models | Genome evolution | Small RNAs | PDF (120 KB)
  - Nat Rev Genet 12(3):155 (2011)
  A high-resolution anatomical atlas of the transcriptome in the mouse embryo Diez-Roux, G.et al. PLoS Biol. 9, e1000582 (2011)Article
• Mutation: The perils of transcription | PDF (168 KB)
  - Nat Rev Genet 12(3):156 (2011)
  Although vital, transcription is a risky business; in many organisms high levels of transcription are associated with increased spontaneous mutagenesis, and recombination events can be triggered by conflicts between transcription and replication. Three new papers shed light on how the genome is normally protected from mutation during transcription.
• Human genomics | Population genetics | Functional genomics | Development | PDF (117 KB)
  - Nat Rev Genet 12(3):156 (2011)
  Mapping copy number variation by population-scale genome sequencing Mills, R. E.et al. Nature 470, 59–65 (2011)
• Sex-chromosome evolution: recent progress and the influence of male and female heterogamety
  - Nat Rev Genet 12(3):157 (2011)
  It is now clear that sex chromosomes differ from autosomes in many aspects of genome biology, such as organization, gene content and gene expression. Moreover, sex linkage has numerous evolutionary genetic implications. Here, I provide a coherent overview of sex-chromosome evolution and function based on recent data. Heteromorphic sex chromosomes are almost as widespread across the animal and plant kingdoms as sexual reproduction itself and an accumulating body of genetic data reveals interesting similarities, as well as dissimilarities, between organisms with XY or ZW sex-determination systems. Therefore, I discuss how patterns and processes associated with sex linkage in male- and female-heterogametic systems offer a useful contrast in the study of sex-chromosome evolution.
• Cleft lip and palate: understanding genetic and environmental influences
  - Nat Rev Genet 12(3):167 (2011)
  Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or teratogenic syndromes. Although there has been marked progress in identifying genetic and environmental triggers for syndromic CLP, the aetiology of the more common non-syndromic (isolated) forms remains poorly characterized. Recently, using a combination of epidemiology, careful phenotyping, genome-wide association studies and analysis of animal models, several distinct genetic and environmental risk factors have been identified and confirmed for non-syndromic CLP. These findings have advanced our understanding of developmental biology and created new opportunities for clinical translational research.
• Improving human forensics through advances in genetics, genomics and molecular biology
  - Nat Rev Genet 12(3):179 (2011)
  Forensic DNA profiling currently allows the identification of persons already known to investigating authorities. Recent advances have produced new types of genetic markers with the potential to overcome some important limitations of current DNA profiling methods. Moreover, other developments are enabling completely new kinds of forensically relevant information to be extracted from biological samples. These include new molecular approaches for finding individuals previously unknown to investigators, and new molecular methods to support links between forensic sample donors and criminal acts. Such advances in genetics, genomics and molecular biology are likely to improve human forensic case work in the near future.
• The sociobiology of molecular systems
  - Nat Rev Genet 12(3):193 (2011)
  It is often assumed that molecular systems are designed to maximize the competitive ability of the organism that carries them. In reality, natural selection acts on both cooperative and competitive phenotypes, across multiple scales of biological organization. Here I ask how the potential for social effects in evolution has influenced molecular systems. I discuss a range of phenotypes, from the selfish genetic elements that disrupt genomes, through metabolism, multicellularity and cancer, to behaviour and the organization of animal societies. I argue that the balance between cooperative and competitive evolution has shaped both form and function at the molecular scale.
• The pleiotropic structure of the genotypeâ€"phenotype map: the evolvability of complex organisms
  - Nat Rev Genet 12(3):204 (2011)
  It was first noticed 100 years ago that mutations tend to affect more than one phenotypic characteristic, a phenomenon that was called 'pleiotropy'. Because pleiotropy was found so frequently, the notion arose that pleiotropy is 'universal'. However, quantitative estimates of pleiotropy have not been available until recently. These estimates show that pleiotropy is highly restricted and are more in line with the notion of variational modularity than with universal pleiotropy. This finding has major implications for the evolvability of complex organisms and the mapping of disease-causing mutations.
• The importance of phase information for human genomics
  - Nat Rev Genet 12(3):215 (2011)
  Contemporary sequencing studies often ignore the diploid nature of the human genome because they do not routinely separate or 'phase' maternally and paternally derived sequence information. However, many findings — both from recent studies and in the more established medical genetics literature — indicate that relationships between human DNA sequence and phenotype, including disease, can be more fully understood with phase information. Thus, the existing technological impediments to obtaining phase information must be overcome if human genomics is to reach its full potential.
• Correspondence: Big data, but are we ready?
  - Nat Rev Genet 12(3):224 (2011)
  We welcome the timely Review by Schadt et al. (Computational solutions to large-scale data management and analysis.Nature Rev. Genet. 11, 647–657 (2010)