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:

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  - 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.