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:

• 
  - 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.

Hot off the presses! May 01

The May 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:

• 
  - Nature reviews. Genetics 11(5):309 (2010)
  
• 
  - Nature reviews. Genetics 11(5):310 (2010)
  
• Disease genetics: Whole-genome sequencing identifies Mendelian mutations | PDF (206 KB)
  - Nature reviews. Genetics 11(5):313 (2010)
  Sequencing complete patient genomes to determine the precise genetic causes of human diseases is becoming increasingly feasible. However, until the cost drops sufficiently to allow sequencing of large sample sizes â€" which will be needed if common diseases are to be investigated â€" one prioritization strategy is family-based sequencing to identify mutations that underlie Mendelian diseases.
• Regeneration: Mouse, heal thyself | PDF (198 KB)
  - Nature reviews. Genetics 11(5):314 (2010)
  Unlike champion regenerators, such as sponges, flatworms, hydras and newts, the ability to regenerate appendages is lacking in mammals. A new study in mice takes advantage of a rare exception to this rule to identify a tumour suppressor gene as a regulator of regenerative capacity in mammals.
• Complex traits: Plants are not humans | PDF (189 KB)
  - Nature reviews. Genetics 11(5):314 (2010)
  Advances in genomics have made it possible to use genome-wide association (GWA) studies to explore the genetic basis of common traits in humans, leading to advances in biological knowledge and technical expertise. The power of the GWA approach has now been extended successfully to Arabidopsis thaliana, in which results are proving to be strikingly different from those obtained in humans.
• Gene expression | Sex determination | Association studies | Nuclear organization | PDF (156 KB)
  - Nature reviews. Genetics 11(5):314 (2010)
  Gene expression Deciphering normal blood gene expression variation â€" the NOWAC postgenome study Dumeaux, V. et al. PLoS Genet. 6, e1000873 (2010) To use gene expression profiles as biomarkers for medical conditions or environmental exposures, a baseline pattern of gene expression in the general population is needed.
• Functional genomics: Learning to prioritize | PDF (172 KB)
  - Nature reviews. Genetics 11(5):315 (2010)
  The number of species with sequenced genomes is rising rapidly, but annotating the protein functions encoded in these genomes from scratch would be an expensive and time-consuming process. Instead, as a recent study shows, existing data from model organisms can be used to design a streamlined set of experiments to annotate the genomes of related species.
• Gene expression: Standing out from the crowd | PDF (181 KB)
  - Nature reviews. Genetics 11(5):316 (2010)
  Most gene-expression studies sample populations of cells and so have limitations for answering many questions about cell fate or specialization. The technical challenges of how to obtain accurate data on cell-to-cell variation and how to identify cell-type-specific patterns from heterogeneous tissue samples have been addressed in two recent papers.
• Evolution: Where sexes collide | PDF (188 KB)
  - Nature reviews. Genetics 11(5):316 (2010)
  The males and females of many species have different interests at heart; this is reflected in their appearance, behaviour and, ultimately, in their DNA, in which genes are evolutionarily torn as to whether to benefit one sex or the other. A study in fruitflies has mapped the loci at which this genomic tug-of-war takes place and shows that such genes abound on the X chromosome.
• Complex disease | Epigenetics | Chromosome biology | PDF (139 KB)
  - Nature reviews. Genetics 11(5):316 (2010)
  Complex disease Robust replication of genotypeâ€"phenotype associations across multiple diseases in an electronic record Ritchie, M. D. et al. Am. J. Hum.
• Transcriptomics: Seq-ing regulatory variants | PDF (179 KB)
  - Nature reviews. Genetics 11(5):317 (2010)
  Speculation that next-generation sequencing of RNA (RNAâ€"seq) will connect genome variants with variation in gene expression levels has moved towards reality with the publication of two papers describing RNAâ€"seq on well-characterized human populations. Gene expression levels are partly controlled by genetic variation, and microarray expression data have been used to look for associations between sequence variants and expression levels (expression quantitative trait loci (eQTLs)).
• Taking DNA from the dead | PDF (216 KB)
  McGuire AL Majumder MA Halpern SD Swindell JS Yaeger LV Gibbs RA Wheeler TM - Nature reviews. Genetics 11(5):318 (2010)
  Using cadaveric specimens in genome research presents many benefits: investigators can study multiple organs from one individual, including those impossible to collect from living donors (for example, brains), and health risks are minimized as the individual is deceased. Several genomic research initiatives plan to collect cadaveric tissues.
• Alternative lengthening of telomeres: models, mechanisms and implications
  Cesare AJ Reddel RR - Nature reviews. Genetics 11(5):319 (2010)
  Unlimited cellular proliferation depends on counteracting the telomere attrition that accompanies DNA replication. In human cancers this usually occurs through upregulation of telomerase activity, but in 10–15% of cancers — including some with particularly poor outcome — it is achieved through a mechanism known as alternative lengthening of telomeres (ALT). ALT, which is dependent on homologous recombination, is therefore an important target for cancer therapy. Although dissection of the mechanism or mechanisms of ALT has been challenging, recent advances have led to the identification of several genes that are required for ALT and the elucidation of the biological significance of some phenotypic markers of ALT. This has enabled development of a rapid assay of ALT activity levels and the construction of molecular models of ALT.
• The primary cilium: a signalling centre during vertebrate development
  - Nature reviews. Genetics 11(5):331 (2010)
  The primary cilium has recently stepped into the spotlight, as a flood of data show that this organelle has crucial roles in vertebrate development and human genetic diseases. Cilia are required for the response to developmental signals, and evidence is accumulating that the primary cilium is specialized for hedgehog signal transduction. The formation of cilia, in turn, is regulated by other signalling pathways, possibly including the planar cell polarity pathway. The cilium therefore represents a nexus for signalling pathways during development. The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction.
• Alternative splicing and evolution: diversification, exon definition and function
  Keren H Lev-Maor G Ast G - Nature reviews. Genetics 11(5):345 (2010)
  Over the past decade, it has been shown that alternative splicing (AS) is a major mechanism for the enhancement of transcriptome and proteome diversity, particularly in mammals. Splicing can be found in species from bacteria to humans, but its prevalence and characteristics vary considerably. Evolutionary studies are helping to address questions that are fundamental to understanding this important process: how and when did AS evolve? Which AS events are functional? What are the evolutionary forces that shaped, and continue to shape, AS? And what determines whether an exon is spliced in a constitutive or alternative manner? In this Review, we summarize the current knowledge of AS and evolution and provide insights into some of these unresolved questions.
• Genome-wide association studies in diverse populations
  - Nature reviews. Genetics 11(5):356 (2010)
  Genome-wide association (GWA) studies have identified a large number of SNPs associated with disease phenotypes. As most GWA studies have been performed in populations of European descent, this Review examines the issues involved in extending the consideration of GWA studies to diverse worldwide populations. Although challenges exist with issues such as imputation, admixture and replication, investigation of a greater diversity of populations could make substantial contributions to the goal of mapping the genetic determinants of complex diseases for the human population as a whole.
• Synthetic biology: applications come of age
  - Nature reviews. Genetics 11(5):367 (2010)
  Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, 'green' means to fuel our cars and targeted therapies for attacking 'superbugs' and diseases, such as cancer. The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications.
• Mendelian disorders and multifactorial traits: the big divide or one for all?
  - Nature reviews. Genetics 11(5):380 (2010)
  For the past century, Mendelian and multifactorial traits have existed at opposite ends of the disease spectrum in humans. Furthermore, the recent emphasis on genome-wide association studies for uncovering variants that underlie common diseases has risked deepening the divide — or has it? Four experienced human geneticists express their views on the changing landscape of human disease studies and the impact of new technologies and study designs on the age-old aim of connecting a genomic variant with its phenotypic consequences.

Hot off the presses! Mar 01

The Mar 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:

• 
  - Nature reviews. Genetics 11(3):167 (2010)
  
• Evolution: Illusions of conservation | PDF (193 KB)
  - Nature reviews. Genetics 11(3):169 (2010)
  If a sequence or property appears to be conserved across evolutionary time it is often interpreted as being functionally important. But can apparently conserved patterns be produced by neutral or indirect forces? New simulations of regulatory element evolution show that they can.
• Complex disease: Rare treasures | PDF (151 KB)
  - Nature reviews. Genetics 11(3):170 (2010)
  Rare variants distributed across large genomic regions make a substantial contribution to the genetic basis of complex diseases, according to a simulated genome-wide association (GWA) study that is backed by real disease-mapping data. GWA studies are based on the assumption that complex diseases are caused by many common variants of small effect, and the signals observed in GWA studies are assumed to correspond to common variants.
• Human genomics: Into Africa | PDF (199 KB)
  - Nature reviews. Genetics 11(3):170 (2010)
  The steady increase in the number of individual human genome sequences is providing fine-scale insights into variation in the human genome. These insights inform us about human diversity and have important implications for medical applications of genomics.
• Evo–devo: Nasonia tools up | PDF (183 KB)
  - Nature reviews. Genetics 11(3):170 (2010)
  Evolutionary developmental biology (evoâ€"devo) research has been boosted in recent years by expansion in the range of genetically tractable model organisms that can be manipulated in the laboratory. The publication of the genome sequence of three species of the parasitoid wasp Nasonia â€" accompanied by a clutch of papers that have utilized the sequence data â€" is enabling the development of a sophisticated genetic tool kit for this emerging arthropod model.
• Evolution | Population genetics | Splicing | Genetic variation | PDF (154 KB)
  - Nature reviews. Genetics 11(3):171 (2010)
  Evolution Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content Hughes, J. F. et al. Nature 463, 536â€"539 (2010) The authors report the finished sequence of the male-specific region of the Y chromosome (MSY) in chimpanzees. Comparing the MSY sequence of chimpanzees and humans reveals that far from being an evolutionarily stagnant region of the genome, as previously assumed, the two MSYs have in fact been diverging rapidly over the past 6 million years.
• Small RNAs: An epigenetic silencing influence | PDF (227 KB)
  - Nature reviews. Genetics 11(3):172 (2010)
  MicroRNAs (miRNAs) regulate gene expression by base pairing with target RNAs, leading to their cleavage in plants or translational inhibition in animals. Now evidence has emerged that in moss, miRNAs can also silence gene expression at the transcriptional level by interacting with DNA, leading to methylation.
• Gene networks: Meaningful connections | PDF (360 KB)
  - Nature reviews. Genetics 11(3):172 (2010)
  The magnitude and direction of epistasis and the functional consequences of these geneâ€"gene interactions are fundamental to relating genotype to phenotype and thus for informing fields from human disease to speciation. The detailed analysis of global metabolic and genetic interactions in Escherichia coli and Saccharomyces cerevisiae highlights the potential of such surveys for functionally annotating the genome, and also overturns some widely held assumptions.
• Cellular defence: Human cells clear foreign DNA | PDF (162 KB)
  - Nature reviews. Genetics 11(3):172 (2010)
  Foreign DNA poses a security threat to cells â€" for example, by allowing pathogen proteins to be expressed or by disrupting the genome. A mechanism by which human cells clear foreign DNA has now been identified â€" the first time that a DNA restriction system analogous to that of bacteria has been demonstrated in eukaryotes.
• Genome evolution | Plant genetics | Epigenetics | Evo–devo | PDF (154 KB)
  - Nature reviews. Genetics 11(3):173 (2010)
  Genome evolution Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes Chen, C.-L. et al. Genome Res.
• The molecular evolutionary basis of species formation
  - Nature reviews. Genetics 11(3):175 (2010)
  All plant and animal species arise by speciation — the evolutionary splitting of one species into two reproductively incompatible species. But until recently our understanding of the molecular genetic details of speciation was slow in coming and largely limited to Drosophila species. Here, I review progress in determining the molecular identities and evolutionary histories of several new 'speciation genes' that cause hybrid dysfunction between species of yeast, flies, mice and plants. The new work suggests that, surprisingly, the first steps in the evolution of hybrid dysfunction are not necessarily adaptive.
• CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea
  - Nature reviews. Genetics 11(3):181 (2010)
  Sequence-directed genetic interference pathways control gene expression and preserve genome integrity in all kingdoms of life. The importance of such pathways is highlighted by the extensive study of RNA interference (RNAi) and related processes in eukaryotes. In many bacteria and most archaea, clustered, regularly interspaced short palindromic repeats (CRISPRs) are involved in a more recently discovered interference pathway that protects cells from bacteriophages and conjugative plasmids. CRISPR sequences provide an adaptive, heritable record of past infections and express CRISPR RNAs — small RNAs that target invasive nucleic acids. Here, we review the mechanisms of CRISPR interference and its roles in microbial physiology and evolution. We also discuss potential applications of this novel interference pathway.
• Principles and challenges of genome-wide DNA methylation analysis
  - Nature reviews. Genetics 11(3):191 (2010)
  Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. Therefore, profiling DNA methylation across the genome is vital to understanding the influence of epigenetics. There has been a revolution in DNA methylation analysis technology over the past decade: analyses that previously were restricted to specific loci can now be performed on a genome-scale and entire methylomes can be characterized at single-base-pair resolution. However, there is such a diversity of DNA methylation profiling techniques that it can be challenging to select one. This Review discusses the different approaches and their relative merits and introduces considerations for data analysis.
• Establishing, maintaining and modifying DNA methylation patterns in plants and animals
  - Nature reviews. Genetics 11(3):204 (2010)
  Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse biological processes, including gene and transposon silencing, imprinting and X chromosome inactivation. Recent findings in plants and animals have greatly increased our understanding of the pathways used to accurately target, maintain and modify patterns of DNA methylation and have revealed unanticipated mechanistic similarities between these organisms. Key roles have emerged for small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases in these processes. Drawing on insights from both plants and animals should deepen our understanding of the regulation and biological significance of DNA methylation.
• Mammalian recombination hot spots: properties, control and evolution
  - Nature reviews. Genetics 11(3):221 (2010)
  Recombination, together with mutation, generates the raw material of evolution, is essential for reproduction and lies at the heart of all genetic analysis. Recent advances in our ability to construct genome-scale, high-resolution recombination maps and new molecular techniques for analysing recombination products have substantially furthered our understanding of this important biological phenomenon in humans and mice: from describing the properties of recombination hot spots in male and female meiosis to the recombination landscape along chromosomes. This progress has been accompanied by the identification of trans-acting systems that regulate the location and relative activity of individual hot spots.
• Correspondence: Inbreeding effects in the epigenetic era
  - Nature reviews. Genetics 11(3):234 (2010)
  Recent articles by Charlesworth and Willis (The genetics of inbreeding depression. Nature Rev.

Hot off the presses! Feb 01

The Feb 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:

• 
  - Nature reviews. Genetics 11(2):89 (2010)
  Future directions in association studies for complex disease
• Genomics: Building a giant in tiny steps | PDF (290 KB)
  - Nature reviews. Genetics 11(2):91 (2010)
  A milestone in genome sequencing has been achieved with the publication of a draft sequence of the giant panda genome: the first large eukaryotic genome to be assembled de novo using next-generation sequencing technology alone. This paper shows the way to more rapid and cost-effective de novo genome assembly and offers numerous insights for evolutionary and conservation biology.
• Genome architecture: Reliable repositioning in cancer | PDF (246 KB)
  - Nature reviews. Genetics 11(2):92 (2010)
  One of the biggest challenges in cancer is proper diagnosis in the smallest possible amounts of tissue, such as that from a core needle biopsy in potential breast cancer cases. Routine protocols now in place generally rely on the opinion of a trained cytopathologist and have not been automated with any quantifiable assay.
• Signalling: Sensing a change | PDF (199 KB)
  - Nature reviews. Genetics 11(2):92 (2010)
  According to Weber's law, our perception of sensations, such as light or sound, is based not on the absolute level of the stimulus but on the magnitude of the stimulus relative to the background level — explaining why, for example, you might not notice a lit bulb in a bright room but would easily spot the same light after dark. Three papers now present experimental and theoretical evidence that Weber's law also applies to individual cells, by showing that signalling pathways respond to fold-changes in sensor molecules.
• Recombination: The gene that hits the hot spot | PDF (189 KB)
  - Nature reviews. Genetics 11(2):92 (2010)
  Sites of meiotic recombination are highly localized on eukaryotic genomes, but the reason for this remains puzzling. Three papers now identify a histone methyltransferase as a key controller of crossover 'hot spots': a finding that has implications for the molecular control of recombination and its evolution.
• Regulatory elements | Synthetic biology | Gene expression | Human evolution | PDF (150 KB)
  - Nature reviews. Genetics 11(2):93 (2010)
  Regulatory elements Human genetic variation recognizes functional elements in non-coding sequence Lomelin, D., Jorgenson, E.|[nbsp]| & Risch, N. Genome Res. 23 Dec 2009 (doi:10.
• Cancer genomics: Genomic archeology | PDF (191 KB)
  - Nature reviews. Genetics 11(2):94 (2010)
  Tumour cells accumulate somatic mutations over time, some of which are causal and some of which simply come along for the ride. Recent advances in DNA sequencing technologies have made it possible to catalogue these mutations across whole genomes to reveal not only the types of mutation present in a given cancer type but also the mutational processes that created them.
• Complex disease: Adding epigenetics to the mix | PDF (187 KB)
  - Nature reviews. Genetics 11(2):94 (2010)
  Three recent papers highlight the importance of considering epigenetics in the study of both heritable and non-heritable influences on complex human disease. Because of the genetic near-identity between monozygotic twins, cases of discordance provide opportunities to explore non-genetic factors that influence phenotypic differences.
• Epigenetics | Evolution | Plant genetics | Disease models | PDF (154 KB)
  - Nature reviews. Genetics 11(2):95 (2010)
  Epigenetics Essential role of the histone methyltransferase G9a in cocaine-induced plasticity Maze, I. et al. Science 327, 213–216 (2009) Changes in neuronal morphology as a result of repeated exposure to cocaine are thought to underlie addiction to this drug. This paper shows that administration of cocaine to mice causes downregulation of the histone methyltransferase G9a, which leads to a decrease in the repressive chromatin mark histone H3 lysine 9 dimethylation in the region of the brain associated with reward.
• Complex disease: A mutational history of Alzheimer's | PDF (377 KB)
  - Nature reviews. Genetics 11(2):96 (2010)
  A common polymorphism that accelerates the onset of the most common form of Alzheimer's disease (AD) by an average of 7 years has been identified. The polymorphism in question — a poly(T) variant in a mitochondrial translocase gene — was identified using a new phylogenetic mapping approach and only affects individuals who carry the |[epsi]|3 allele of the AD-susceptibility gene, APOE.
• Development: Male versus female | PDF (196 KB)
  - Nature reviews. Genetics 11(2):96 (2010)
  In mammalian embryos the gonad can develop into either an ovary or a testis. The absence of the testis-determination gene, Sry, leads to ovarian development, and this has led to the assumption that the development of female traits is the default pathway.
• The evolution of gene duplications: classifying and distinguishing between models
  - Nature reviews. Genetics 11(2):97 (2010)
  Gene duplications and their subsequent divergence play an important part in the evolution of novel gene functions. Several models for the emergence, maintenance and evolution of gene copies have been proposed. However, a clear consensus on how gene duplications are fixed and maintained in genomes is lacking. Here, we present a comprehensive classification of the models that are relevant to all stages of the evolution of gene duplications. Each model predicts a unique combination of evolutionary dynamics and functional properties. Setting out these predictions is an important step towards identifying the main mechanisms that are involved in the evolution of gene duplications.
• Deconstructing repression: evolving models of co-repressor action
  - Nature reviews. Genetics 11(2):109 (2010)
  A crucial aspect of development, homeostasis and prevention of disease is the strict maintenance of patterns of gene repression. Gene repression is largely achieved by the combinatorial action of various enzymatic complexes — known as co-repressor complexes — that are recruited to DNA by transcription factors and often act through enzymatic modification of histone protein tails. Our understanding of how co-repressors act has begun to change over recent years owing to the increased availability of genome-scale data. Here, we consider specific strategies that underlie repression events — for example, those mediated by the nuclear receptor co-repressor (NCoR, also known as NCOR1) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT, also known as NCOR2) co-repressor complexes — and discuss emerging themes in gene repression.
• Genetics of mammalian meiosis: regulation, dynamics and impact on fertility
  - Nature reviews. Genetics 11(2):124 (2010)
  Meiosis is an essential stage in gamete formation in all sexually reproducing organisms. Studies of mutations in model organisms and of human haplotype patterns are leading to a clearer understanding of how meiosis has adapted from yeast to humans, the genes that control the dynamics of chromosomes during meiosis, and how meiosis is tied to gametic success. Genetic disruptions and meiotic errors have important roles in infertility and the aetiology of developmental defects, especially aneuploidy. An understanding of the regulation of meiosis, coupled with advances in genomics, may ultimately allow us to diagnose the causes of meiosis-based infertilities, more wisely apply assisted reproductive technologies, and derive functional germ cells.
• How culture shaped the human genome: bringing genetics and the human sciences together
  - Nature reviews. Genetics 11(2):137 (2010)
  Researchers from diverse backgrounds are converging on the view that human evolution has been shaped by gene–culture interactions. Theoretical biologists have used population genetic models to demonstrate that cultural processes can have a profound effect on human evolution, and anthropologists are investigating cultural practices that modify current selection. These findings are supported by recent analyses of human genetic variation, which reveal that hundreds of genes have been subject to recent positive selection, often in response to human activities. Here, we collate these data, highlighting the considerable potential for cross-disciplinary exchange to provide novel insights into how culture has shaped the human genome.
• Methodological challenges of genome-wide association analysis in Africa
  - Nature reviews. Genetics 11(2):149 (2010)
  Medical research in Africa has yet to benefit from the advent of genome-wide association (GWA) analysis, partly because the genotyping tools and statistical methods that have been developed for European and Asian populations struggle to deal with the high levels of genome diversity and population structure in Africa. However, the haplotypic diversity of African populations might help to overcome one of the major roadblocks in GWA research, the fine mapping of causal variants. We review the methodological challenges and consider how GWA studies in Africa will be transformed by new approaches in statistical imputation and large-scale genome sequencing.
• Personalized genomic information: preparing for the future of genetic medicine
  - Nature reviews. Genetics 11(2):161 (2010)
  The falling cost of sequencing means that we are rapidly approaching an era in which access to personalized genomic information is likely to be widespread. Here, four experts with different insights into the field of genomic medicine answer questions about the prospects for using this type of information. Their responses highlight the diverse range of issues that must be addressed — ranging from scientific to ethical and logistical — to ensure that the potential benefits of personal genomic information outweigh the costs to both individuals and societies.
• Correspondence: Empirical tests for compositional epistasis
  - Nature reviews. Genetics 11(2):166 (2010)
  In her Review article (Detecting gene–gene interactions that underlie human diseases. Nature Rev.

Hot off the presses! Mar 01

The Mar 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:

• From the editors
  - Nature Reviews Neuroscience 11(3):147 (2010)
  This issue of Nature Reviews Neuroscience contains several articles about aspects of the transmission of information and disease in the nervous system.In his Review on page 188, Benjamin Kaupp compares and contrasts the chemosensory receptors and signalling mechanisms involved in olfaction in vertebrates and insects.
• Neural circuits: Out of synch
  - Nature Reviews Neuroscience 11(3):149 (2010)
  Previous studies have shown correlated spiking activity within local populations of cortical neurons, an effect thought to arise as a result of shared inputs to the neurons. However, two new papers suggest that correlations in firing between neighbouring neurons may be much weaker than was thought.
• Neurological disorders: Striking point for stroke
  - Nature Reviews Neuroscience 11(3):150 (2010)
  Glutamate toxicity as a result of excessive NMDA (N-methyl-D-aspartate) receptor activation is considered the main factor responsible for neuronal death following ischaemia. However, the essential physiological action of these receptors in synaptic transmission means that simply blocking them is not a feasible therapeutic option.
• In brief: Neuronal plasticity, Spatial awareness, Axon Growth, Motor Systems
  - Nature Reviews Neuroscience 11(3):150 (2010)
  Direct conversion of fibroblasts to functional neurons by defined factors Vierbuchen , T.et al. Nature27 January 2010 (doi:10.1038/nature08797)
• Prions: A protective role for prions
  - Nature Reviews Neuroscience 11(3):151 (2010)
  Mutated forms of PrPC, the endogenous prion protein, are linked to transmissible spongiform encephalopathies, but the normal function of PrPC has yet to be identified. Bremer et al.C is necessary for the maintenance of the myelin sheaths around peripheral nerves.
• Sensory processing: Sensing motion with tact
  - Nature Reviews Neuroscience 11(3):151 (2010)
  When we handle an object, the relative movement between its surface and our skin provides the brain with valuable information about its characteristics. The existence of a subpopulation of neurons in the visual cortex that responds specifically to the direction of movement of a visual stimulus is widely known, but it remains unclear whether the perception of tactile motion relies on an analogous mechanism.
• Affective disorders: A faster way to happiness
  - Nature Reviews Neuroscience 11(3):152 (2010)
  Most antidepressants that are currently available take several weeks to exert their effects, and clinical evidence has suggested co-administration of an antagonist of α2-adrenoceptors as a potential strategy to overcome this drawback. However, the mechanisms by which blockade of these receptors accelerates the improvements in mood are still largely unknown.
• Techniques: Zebrafish behaviour in profile
  - Nature Reviews Neuroscience 11(3):152 (2010)
  The complexity of brain function makes it difficult to develop simple high-throughput screens to identify drugs that can target nervous system disorders. Two studies have now addressed this problem by using zebrafish larvae to screen for drugs that affect particular behaviours.
• Neuron–glia interactions: With a little help from glia
  - Nature Reviews Neuroscience 11(3):152 (2010)
  Whether glia cells are involved in the induction of long-term potentiation (LTP) — a form of synaptic plasticity — in vivo remains controversial. Rusakov and colleagues now show that Ca2+-dependent D-serine release from astrocytes regulates NMDAR (N-methyl-D-aspartate receptor)-dependent synaptic plasticity in acute hippocampal slice preparations from adult rats, providing evidence for such an involvement.
• In brief: Development, Memory, Stress, Neurodegenerative diseases
  - Nature Reviews Neuroscience 11(3):153 (2010)
  Local and long-range reciprocal regulation of cAMP and cGMP in axon/dendrite formation Shelley , M.et al. Science 327, 547–552 (2010)How do undifferentiated neurites develop to produce one axon and multiple dendrites per neuron?
• Prion-like mechanisms in neurodegenerative diseases
  Frost B Diamond MI - Nature Reviews Neuroscience 11(3):155 (2010)
  Many non-infectious neurodegenerative diseases are associated with the accumulation of fibrillar proteins. These diseases all exhibit features that are reminiscent of those of prionopathies, including phenotypic diversity and the propagation of pathology. Furthermore, emerging studies of amyloid-β, α-synuclein and tau — proteins implicated in common neurodegenerative diseases — suggest that they share key biophysical and biochemical characteristics with prions. Propagation of protein misfolding in these diseases may therefore occur through mechanisms similar to those that underlie prion pathogenesis. If this hypothesis is verified in vivo, it will suggest new therapeutic strategies to block propagation of protein misfolding throughout the brain.
• Protein palmitoylation in neuronal development and synaptic plasticity
  - Nature Reviews Neuroscience 11(3):161 (2010)
  Protein palmitoylation, a classical and common lipid modification, regulates diverse aspects of neuronal protein trafficking and function. The reversible nature of palmitoylation provides a potential general mechanism for protein shuttling between intracellular compartments. The recent discovery of palmitoylating enzymes — a large DHHC (Asp-His-His-Cys) protein family — and the development of new proteomic and imaging methods have accelerated palmitoylation analysis. It is becoming clear that individual DHHC enzymes generate and maintain the specialized compartmentalization of substrates in polarized neurons. Here, we discuss the regulatory mechanisms for dynamic protein palmitoylation and the emerging roles of protein palmitoylation in various aspects of pathophysiology, including neuronal development and synaptic plasticity.
• Neural stem cell systems: physiological players or in vitro entities?
  - Nature Reviews Neuroscience 11(3):176 (2010)
  Neural stem cells (NSCs) can be experimentally derived or induced from different sources, and the NSC systems generated so far are promising tools for basic research and biomedical applications. However, no direct and thorough comparison of their biological and molecular properties or of their physiological relevance and possible relationship to endogenous NSCs has yet been carried out. Here we review the available information on different NSC systems and compare their properties. A better understanding of these systems will be crucial to control NSC fate and functional integration following transplantation and to make NSCs suitable for regenerative efforts following injury or disease.
• Olfactory signalling in vertebrates and insects: differences and commonalities
  Kaupp UB - Nature Reviews Neuroscience 11(3):188 (2010)
  Vertebrates and insects have evolved complex repertoires of chemosensory receptors to detect and distinguish odours. With a few exceptions, vertebrate chemosensory receptors belong to the family of G protein-coupled receptors that initiate a cascade of cellular signalling events and thereby electrically excite the neuron. Insect receptors, which are structurally and genetically unrelated to vertebrate receptors, are a complex of two distinct molecules that serves both as a receptor for the odorant and as an ion channel that is gated by binding of the odorant. Metabotropic signalling in vertebrates provides a rich panoply of positive and negative regulation, whereas ionotropic signalling in insects enhances processing speed.
• The neuroscience of human intelligence differences
  Deary IJ Penke L Johnson W - Nature Reviews Neuroscience 11(3):201 (2010)
  Neuroscience is contributing to an understanding of the biological bases of human intelligence differences. This work is principally being conducted along two empirical fronts: genetics — quantitative and molecular — and brain imaging. Quantitative genetic studies have established that there are additive genetic contributions to different aspects of cognitive ability — especially general intelligence — and how they change through the lifespan. Molecular genetic studies have yet to identify reliably reproducible contributions from individual genes. Structural and functional brain-imaging studies have identified differences in brain pathways, especially parieto-frontal pathways, that contribute to intelligence differences. There is also evidence that brain efficiency correlates positively with intelligence.
• Chemosensory organs as models of neuronal synapses
  Shaham S - Nature Reviews Neuroscience 11(3):212 (2010)
  Neuronal synapses are important microstructures that underlie complex cognitive capacities. Recent studies, primarily in Caenorhabditis elegans and Drosophila melanogaster, have revealed surprising parallels between these synapses and the 'chemosensory synapses' that reside at the tips of chemosensory cells that respond to environmental stimuli. Similarities in the structures, mechanisms of action and specific molecules found at these sites extend to the presynaptic, postsynaptic and glial entities composing both synapse types. In this article I propose that chemosensory synapses may serve as useful models of neuronal synapses, and consider the possibility that the two synapse types derive from a common ancestral structure.
• Correspondence: Overnight alchemy: sleep-dependent memory evolution
  - Nature Reviews Neuroscience 11(3):218 (2010)
  Diekelmann and Born offer an elegant and convincing overview of evidence supporting the role of sleep in the consolidation of newly acquired memories (The memory function of sleep. Nature Rev. Neurosci. 11, 114–126 (2010)
• Correspondence: Slow-wave sleep takes the leading role in memory reorganization
  - Nature Reviews Neuroscience 11(3):218 (2010)
  We recently proposed a comprehensive framework for sleep-dependent memory consolidation suggesting that, during slow-wave sleep (SWS), memory representations are transferred from a temporary to a long-term store and thereby undergo reorganization in a process of system consolidation (The memory function of sleep. Nature Rev. Neurosci. 11, 114–126 (2010)
• Corrigendum: CART peptides: regulators of body weight, reward and other functions
  - Nature Reviews Neuroscience 11(3):218 (2010)
  In figure 4a of the article, the doses of the bilateral CART (cocaine- and amphetamine-regulated transcript) peptide infusions were incorrectly given in milligrams. In both the figure and the legend, the doses should be 0.0, 1.0 or 2.5 μg per side.