Friday, September 16, 2011

Hot off the presses! Oct 01 Nat Rev Genet

The Oct 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:

  • - Nat Rev Genet 12(10):665 (2011)
  • Genomic instability: Aneuploidy stokes the fire | PDF (426 KB)
    - Nat Rev Genet 12(10):666 (2011)
    Whole-chromosome aneuploidy — that is, irregular numbers of individual chromosomes — is frequently observed in tumours. There is considerable debate about whether aneuploidy is a cause or merely a consequence of the interlinked phenomena of genomic instability and tumorigenesis; however, two new reports provide further evidence for a causal role for aneuploidy in both.
  • Quantitative traits: Gender inequalities | PDF (250 KB)
    - Nat Rev Genet 12(10):667 (2011)
    A large-scale population study has uncovered significant differences between the metabolite profiles of men and women, and it has identified SNPs that are associated with the sexual dimorphism of one particular metabolite. This work underscores the importance of stratifying by sex in trait-mapping studies.
  • Technology: Keeping ZFNs on target | PDF (277 KB)
    - Nat Rev Genet 12(10):667 (2011)
    The ability of engineered zinc finger nucleases (ZFNs) to target a specific DNA site for modification makes them an attractive option for genome manipulation in basic and applied research. Two studies of ZFN specificity now show that the in vivo off-target sites of ZFN cleavage cannot be fully predicted by in vitro or in silico analysis.
  • Synthetic biology: Licensing bacteria to kill | PDF (145 KB)
    - Nat Rev Genet 12(10):668 (2011)
    The introduction of synthetic genetic systems into bacteria holds much promise for the production of drugs and biofuels and for the bioremediation of contaminated environments. With the design and testing of an engineered Escherichia coli strain that specifically targets Pseudomonas aeruginosa, Saeidi et al.
  • Translational genetics: Signatures for drug repositioning | PDF (200 KB)
    - Nat Rev Genet 12(10):668 (2011)
    Identifying new therapeutic uses for approved drugs — known as drug repositioning — can reduce development costs and accelerate regulatory approval. Two recent studies, led by the same group of researchers, used computational analysis of publicly available gene expression data to suggest potential new therapeutic uses for approved drugs.
  • Gene therapy | Evolution | Comparative genomics | Technology | PDF (88 KB)
    - Nat Rev Genet 12(10):668 (2011)
    Stem cell-mediated transfer of a human artificial chromosome ameliorates muscular dystrophy Tedesco, F. al. Sci. Transl. Med. 3, 96ra78 (2011)
  • Chromosome biology | Transcriptomics | Epigenetics | Evolution | PDF (74 KB)
    - Nat Rev Genet 12(10):669 (2011)
    Chromosome organization by a nucleoid-associated protein in live bacteria Wang, al. Science 333, 1445–1449 (2011)
  • Ethics watch: Direct-access genetic testing: the view from Europe | PDF (204 KB)
    - Nat Rev Genet 12(10):670 (2011)
    The issues surrounding direct-to-consumer (DTC) genetic testing in North America have received much attention, but far less has been written about how these issues relate to Europe. Here we highlight some key contrasts between the two regions.
  • Next-generation transcriptome assembly
    - Nat Rev Genet 12(10):671 (2011)
    Transcriptomics studies often rely on partial reference transcriptomes that fail to capture the full catalogue of transcripts and their variations. Recent advances in sequencing technologies and assembly algorithms have facilitated the reconstruction of the entire transcriptome by deep RNA sequencing (RNA-seq), even without a reference genome. However, transcriptome assembly from billions of RNA-seq reads, which are often very short, poses a significant informatics challenge. This Review summarizes the recent developments in transcriptome assembly approaches — reference-based, de novo and combined strategies — along with some perspectives on transcriptome assembly in the near future.
  • Understanding the contribution of synonymous mutations to human disease
    - Nat Rev Genet 12(10):683 (2011)
    Synonymous mutations — sometimes called 'silent' mutations — are now widely acknowledged to be able to cause changes in protein expression, conformation and function. The recent increase in knowledge about the association of genetic variants with disease, particularly through genome-wide association studies, has revealed a substantial contribution of synonymous SNPs to human disease risk and other complex traits. Here we review current understanding of the extent to which synonymous mutations influence disease, the various molecular mechanisms that underlie these effects and the implications for future research and biomedical applications.
  • The evolutionary origin of orphan genes
    - Nat Rev Genet 12(10):692 (2011)
    Gene evolution has long been thought to be primarily driven by duplication and rearrangement mechanisms. However, every evolutionary lineage harbours orphan genes that lack homologues in other lineages and whose evolutionary origin is only poorly understood. Orphan genes might arise from duplication and rearrangement processes followed by fast divergence; however, de novo evolution out of non-coding genomic regions is emerging as an important additional mechanism. This process appears to provide raw material continuously for the evolution of new gene functions, which can become relevant for lineage-specific adaptations.
  • Haplotype phasing: existing methods and new developments
    - Nat Rev Genet 12(10):703 (2011)
    Determination of haplotype phase is becoming increasingly important as we enter the era of large-scale sequencing because many of its applications, such as imputing low-frequency variants and characterizing the relationship between genetic variation and disease susceptibility, are particularly relevant to sequence data. Haplotype phase can be generated through laboratory-based experimental methods, or it can be estimated using computational approaches. We assess the haplotype phasing methods that are available, focusing in particular on statistical methods, and we discuss the practical aspects of their application. We also describe recent developments that may transform this field, particularly the use of identity-by-descent for computational phasing.
  • Functional consequences of developmentally regulated alternative splicing
    - Nat Rev Genet 12(10):715 (2011)
    Genome-wide analyses of metazoan transcriptomes have revealed an unexpected level of mRNA diversity that is generated by alternative splicing. Recently, regulatory networks have been identified through which splicing promotes dynamic remodelling of the transcriptome to promote physiological changes, which involve robust and coordinated alternative splicing transitions. The regulation of splicing in yeast, worms, flies and vertebrates affects a variety of biological processes. The functional classes of genes that are regulated by alternative splicing include both those with widespread homeostatic activities and those with cell-type-specific functions. Alternative splicing can drive determinative physiological change or can have a permissive role by providing mRNA variability that is used by other regulatory mechanisms.
  • Assessing and managing risk when sharing aggregate genetic variant data
    - Nat Rev Genet 12(10):730 (2011)
    Access to genetic data across studies is an important aspect of identifying new genetic associations through genome-wide association studies (GWASs). Meta-analysis across multiple GWASs with combined cohort sizes of tens of thousands of individuals often uncovers many more genome-wide associated loci than the original individual studies; this emphasizes the importance of tools and mechanisms for data sharing. However, even sharing summary-level data, such as allele frequencies, inherently carries some degree of privacy risk to study participants. Here we discuss mechanisms and resources for sharing data from GWASs, particularly focusing on approaches for assessing and quantifying the privacy risks to participants that result from the sharing of summary-level data.
  • Sex-chromosome evolution: recent progress and the influence of male and female heterogamety
    - Nat Rev Genet 12(10):736 (2011)
    In figure 1a of the above article, the evolutionary strata (S1–S5) on the human X chromosome were incorrectly labelled. The figure showed the strata in the order S1 to S5, with S1 adjacent to the pseudoautosomal region. The order should be reversed (S5 to S1), with S5 adjacent to the pseudoautosomal region instead. The figure has been amended accordingly, and the corrected article is available at The author apologizes for this error.

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