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:

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  - Nature reviews. Genetics 11(5):309 (2010)
  
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  - 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.