Hot off the presses! Jan 01

The Jan 01 issue of the is now up on Pubget (About ): 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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  - Nature reviews. Genetics 11(1):1 (2010)
  
• Systems biology: Small genome, complex regulation | PDF (226 KB)
  - Nature reviews. Genetics 11(1):3 (2010)
  Three papers describe transcriptomic, metabolic and proteomic analyses of Mycoplasma pneumoniae, which has one of the smallest genomes among self-replicating bacteria. These studies reveal a surprising degree of complexity at each level, which is not only informative about life with a reduced genome but also provides insights into the regulation of cellular functions in bacteria.
• Human disease: Edges, nodes and networks | PDF (174 KB)
  - Nature reviews. Genetics 11(1):4 (2010)
  Classical models of genotype-to-phenotype relationships for human Mendelian disorders generally assume that a mutation causes complete loss of a gene product. A recent paper shows that an alternative, network-based approach is better suited to explain observed phenotypes.
• Bioinformatics: SNPs while you wait | PDF (126 KB)
  - Nature reviews. Genetics 11(1):4 (2010)
  Computational power is struggling to keep pace with the amount of genome variation data that are being collected. One solution is offered by an open access software tool, Crossbow, that allows billions of bases of sequence to be compared and SNP-genotyped accurately and cheaply in a few hours.
• Regulatory elements: A metamorphosis in synthesis | PDF (183 KB)
  - Nature reviews. Genetics 11(1):4 (2010)
  If your aim is to understand functional regulatory elements in genomes or to use them to synthesize new genetic circuits, there is good news: no more need to bother with the tedious work of checking the effects of each possible mutation in a promoter, one base at a time. A new technique by Patwardhan et al. will allow labs to test all mutations at once, given access to a number of ultra-high-throughput technologies.
• Developmental biology | Sex determination | Gene regulation | Differentiation | PDF (121 KB)
  - Nature reviews. Genetics 11(1):5 (2010)
  Developmental biology Chiral blastomere arrangement dictates zygotic left–right asymmetry pathway in snails Kuroda, R. et al. Nature 25 Nov 2009 (doi:10.1038/nature08597) The establishment of left–right (L/R) patterning can be investigated in embryos of the snail Lymnaea stagnalis, in which shells coil clockwise or anticlockwise.
• Small RNAs: Sorting the strands | PDF (210 KB)
  - Nature reviews. Genetics 11(1):6 (2010)
  Before they become associated with Argonaute (AGO) proteins to exert their regulatory effects, microRNAs (miRNAs) exist in a duplex with a complementary miRNA|[ast]| strand. Until recently, only the miRNA strand was thought to be sorted to AGO, and miRNA|[ast]|s were thought to be degraded as non-functional by-products of miRNA metabolism.
• Genomics: Maize looks set to amaze | PDF (147 KB)
  - Nature reviews. Genetics 11(1):6 (2010)
  A genome sequence for maize has long been expected to provide valuable information for both breeding strategies and basic research. Now, publication of the sequence of the B73 inbred maize line, a maize haplotype map and a collection of related papers have demonstrated the breadth of novel insights that can be obtained from this resource.
• Genome evolution | Chromatin | Structural variation | Small RNAs | PDF (122 KB)
  - Nature reviews. Genetics 11(1):7 (2010)
  Genome evolution Ubiquitous internal gene duplication and intron creation in eukaryotes Gao, X. & Lynch, M. Proc. Natl Acad.
• Cancer: Small losses, big gains with microRNAs | PDF (113 KB)
  - Nature reviews. Genetics 11(1):8 (2010)
  A new study in mice shows that heterozygous loss of Dicer, a crucial component of the microRNA (miRNA) processing machinery, could potentially explain the global decrease in miRNA expression often seen in tumours. Homozygous loss of Dicer1 results in embryonic lethality, so targeted deletion of this gene has been investigated.
• Population genetics: SNPs that come in threes | PDF (146 KB)
  - Nature reviews. Genetics 11(1):8 (2010)
  Single-nucleotide polymorphisms (SNPs) are the bread and butter of many studies of sequence variation, and so understanding how they vary is useful to studies of genome evolution and disease susceptibility. Most human SNPs are biallelic — that is, two allelic variants are segregating in the population — but a paper now shows that there are twice as many triallelic SNPs as expected, and puts forward a mutational mechanism by which they might arise.
• Prokaryotic transcriptomics: a new view on regulation, physiology and pathogenicity
  Sorek R Cossart P - Nature reviews. Genetics 11(1):9 (2010)
  Transcriptome-wide studies in eukaryotes have been instrumental in the characterization of fundamental regulatory mechanisms for more than a decade. By contrast, in prokaryotes (bacteria and archaea) whole-transcriptome studies have not been performed until recently owing to the general view that microbial gene structures are simple, as well as technical difficulties in enriching for mRNAs that lack poly(A) tails. Deep RNA sequencing and tiling array studies are now revolutionizing our understanding of the complexity, plasticity and regulation of microbial transcriptomes.
• From evolutionary genetics to human immunology: how selection shapes host defence genes
  - Nature reviews. Genetics 11(1):17 (2010)
  Pathogens have always been a major cause of human mortality, so they impose strong selective pressure on the human genome. Data from population genetic studies, including genome-wide scans for selection, are providing important insights into how natural selection has shaped immunity and host defence genes in specific human populations and in the human species as a whole. These findings are helping to delineate genes that are important for host defence and to increase our understanding of how past selection has had an impact on disease susceptibility in modern populations. A tighter integration between population genetic studies and immunological phenotype studies is now necessary to reveal the mechanisms that have been crucial for our past and present survival against infection.
• Sequencing technologies — the next generation
  Metzker ML - Nature reviews. Genetics 11(1):31 (2010)
  Demand has never been greater for revolutionary technologies that deliver fast, inexpensive and accurate genome information. This challenge has catalysed the development of next-generation sequencing (NGS) technologies. The inexpensive production of large volumes of sequence data is the primary advantage over conventional methods. Here, I present a technical review of template preparation, sequencing and imaging, genome alignment and assembly approaches, and recent advances in current and near-term commercially available NGS instruments. I also outline the broad range of applications for NGS technologies, in addition to providing guidelines for platform selection to address biological questions of interest.
• Origin and evolution of the adaptive immune system: genetic events and selective pressures
  Flajnik MF Kasahara M - Nature reviews. Genetics 11(1):47 (2010)
  The adaptive immune system (AIS) in mammals, which is centred on lymphocytes bearing antigen receptors that are generated by somatic recombination, arose approximately 500 million years ago in jawed fish. This intricate defence system consists of many molecules, mechanisms and tissues that are not present in jawless vertebrates. Two macroevolutionary events are believed to have contributed to the genesis of the AIS: the emergence of the recombination-activating gene (RAG) transposon, and two rounds of whole-genome duplication. It has recently been discovered that a non-RAG-based AIS with similarities to the jawed vertebrate AIS — including two lymphoid cell lineages — arose in jawless fish by convergent evolution. We offer insights into the latest advances in this field and speculate on the selective pressures that led to the emergence and maintenance of the AIS.
• Kinase mutations in human disease: interpreting genotype–phenotype relationships
  - Nature reviews. Genetics 11(1):60 (2010)
  Protein kinases are one of the largest families of evolutionarily related proteins and comprise one of the most abundant gene families in humans. Here we survey kinase gene mutations from the perspective of human disease phenotypes and further analyse the structural features of mutant kinases, including mutational hotspots. Our evaluation of the genotype–phenotype relationship across 915 human kinase mutations — that underlie 67 single-gene diseases, mainly inherited developmental and metabolic disorders and also certain cancers — enhances our understanding of the role of kinases in development, kinase dysfunction in pathogenesis and kinases as potential targets for therapy.
• RNA processing and its regulation: global insights into biological networks
  - Nature reviews. Genetics 11(1):75 (2010)
  In recent years views of eukaryotic gene expression have been transformed by the finding that enormous diversity can be generated at the RNA level. Advances in technologies for characterizing RNA populations are revealing increasingly complete descriptions of RNA regulation and complexity; for example, through alternative splicing, alternative polyadenylation and RNA editing. New biochemical strategies to map protein–RNA interactions in vivo are yielding transcriptome-wide insights into mechanisms of RNA processing. These advances, combined with bioinformatics and genetic validation, are leading to the generation of functional RNA maps that reveal the rules underlying RNA regulation and networks of biologically coherent transcripts. Together these are providing new insights into molecular cell biology and disease.