Hot off the presses! Jan 01 Nat Rev Genet

The Jan 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:

• Evo–devo: Plastic flies | PDF (311 KB)
  - Nat Rev Genet 13(1):1 (2012)
  A study in Drosophila melanogaster shows that variation in how different organs respond to developmental malnutrition is regulated by the expression level of the forkhead transcription factor FOXO. This work suggests that variation in phenotypic plasticity — that is, the ability of a genotype to produce varied phenotypic outcomes, depending on the environment — might have a simple developmental basis.
• Gene regulation: RNAi gets stuck into transcription | PDF (167 KB)
  - Nat Rev Genet 13(1):2 (2012)
  RNAi is best known for its various roles in post-transcriptional gene silencing in the cytoplasm. It is also known to have nuclear functions associated with repressive chromatin or gene silencing, such as the formation of heterochromatin in some species.
• Gene expression: Splicing steps aside to consider its options | PDF (166 KB)
  - Nat Rev Genet 13(1):2 (2012)
  Splicing of precursor mRNAs generally occurs co-transcriptionally, thus promoting the correct sequential splicing of exons as they emerge from RNA polymerase II. However, for alternatively spliced exons, deferring splicing until all of the optional exons have been synthesized would be beneficial.
• Human evolution: Pathogen influence on human genetic variation | PDF (235 KB)
  - Nat Rev Genet 13(1):4 (2012)
  Human population genetic variation is known to be influenced by environmental pressures. By developing a novel statistical framework, Fumagalli and colleagues have been able to discern the relative contributions of environmental factors to evolution of genomes, and they found that local pathogen diversity had the strongest role in the selective process.
• Bacterial evolution: Parallel lives | PDF (170 KB)
  - Nat Rev Genet 13(1):4 (2012)
  The increased availability of high-throughput whole-genome sequencing has facilitated analysis of the transmission and evolution of bacterial pathogens during disease outbreaks. To date, however, it has been difficult to separate adaptive mutations, which confer a benefit, from neutral mutations, which have no impact on fitness.
• Human genetics: Pleiotropic mutations | PDF (131 KB)
  - Nat Rev Genet 13(1):5 (2012)
  A large-scale analysis of SNPs and genes that are reported to be associated with common complex diseases and traits has found abundant pleiotropy: that is, each individual gene mutation may have a role in multiple diseases.
• Genomic instability: Close-up on cancer copy number alterations | PDF (283 KB)
  - Nat Rev Genet 13(1):5 (2012)
  Somatic copy number alterations (SCNAs) are common drivers of tumorigenesis. Two new computational studies have investigated the genomic features that influence which loci are affected by SCNAs, revealing that shared nuclear localization and replication timing could be key determinants.
• Human disease: Pathogenic conversions | PDF (90 KB)
  - Nat Rev Genet 13(1):2 (2012)
  The authors have investigated the deleterious impact of interlocus gene conversion (IGC) — that is, non-reciprocal recombination between paralogous sequences — in inherited human disease. A genome-wide computational approach carried out on >60,000 known disease mutations in >3,000 genes showed that ~1% of these genes contained pathological mutations resulting from ICG.
• 
  - Nat Rev Genet 13(1):2 (2012)
  
• 
  - Nat Rev Genet 13(1):2 (2012)
  
• 
  - Nat Rev Genet 13(1):2 (2012)
  
• 
  - Nat Rev Genet 13(1):3 (2012)
  
• 
  - Nat Rev Genet 13(1):3 (2012)
  
• 
  - Nat Rev Genet 13(1):3 (2012)
  
• 
  - Nat Rev Genet 13(1):3 (2012)
  
• Uncovering the role of 5-hydroxymethylcytosine in the epigenome
  - Nat Rev Genet 13(1):7 (2012)
  Just over 2 years ago, TET1 was found to catalyse the oxidation of 5-methylcytosine, a well-known epigenetic mark, into 5-hydroxymethylcytosine in mammalian DNA. The exciting prospect of a novel epigenetic modification that may dynamically regulate DNA methylation has led to the rapid accumulation of publications from a wide array of fields, from biochemistry to stem cell biology. Although we have only started to scratch the surface, interesting clues on the role of 5-hydroxymethylcytosine are quickly emerging.
• Genomically humanized mice: technologies and promises
  - Nat Rev Genet 13(1):14 (2012)
  Mouse models have become an invaluable tool for understanding human health and disease owing to our ability to manipulate the mouse genome exquisitely. Recent progress in genomic analysis has led to an increase in the number and type of disease-causing mutations detected and has also highlighted the importance of non-coding regions. As a result, there is increasing interest in creating 'genomically' humanized mouse models, in which entire human genomic loci are transferred into the mouse genome. The technical challenges towards achieving this aim are large but are starting to be tackled with success.
• Emerging biomedical applications of synthetic biology
  - Nat Rev Genet 13(1):21 (2012)
  Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications.
• Repetitive DNA and next-generation sequencing: computational challenges and solutions
  - Nat Rev Genet 13(1):36 (2012)
  Repetitive DNA sequences are abundant in a broad range of species, from bacteria to mammals, and they cover nearly half of the human genome. Repeats have always presented technical challenges for sequence alignment and assembly programs. Next-generation sequencing projects, with their short read lengths and high data volumes, have made these challenges more difficult. From a computational perspective, repeats create ambiguities in alignment and assembly, which, in turn, can produce biases and errors when interpreting results. Simply ignoring repeats is not an option, as this creates problems of its own and may mean that important biological phenomena are missed. We discuss the computational problems surrounding repeats and describe strategies used by current bioinformatics systems to solve them.
• Experimental and analytical tools for studying the human microbiome
  - Nat Rev Genet 13(1):47 (2012)
  The human microbiome substantially affects many aspects of human physiology, including metabolism, drug interactions and numerous diseases. This realization, coupled with ever-improving nucleotide sequencing technology, has precipitated the collection of diverse data sets that profile the microbiome. In the past 2 years, studies have begun to include sufficient numbers of subjects to provide the power to associate these microbiome features with clinical states using advanced algorithms, increasing the use of microbiome studies both individually and collectively. Here we discuss tools and strategies for microbiome studies, from primer selection to bioinformatics analysis.
• Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence
  - Nat Rev Genet 13(1):59 (2012)
  Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.
• Molecular spandrels: tests of adaptation at the genetic level
  - Nat Rev Genet 13(1):70 (2012)
  Nature Reviews Genetics12, 767–780 (2011) Table 1 and Supplementary information S1 (table) of this Review incorrectly stated that estimates of selection had not been calculated for the Ace1 gene, a variant of which confers insecticide resistance in mosquitoes. The tables also contained a spelling mistake: the species name Culex pipiens was originally given as Culex pipens in the 'Phenotypic effect' column. The revised tables now include four new papers (listed as references 150 to 153 in the reference list) that discuss the relevant selection studies, and the misspelling of Culex pipiens has been corrected. The four new references for Table 1 and Supplementary information S1 (table) are listed below. Reference 150 is as follows: Lenormand, T., Guillemaud, T., Bourguet, D. & Raymond, M. Evaluating gene flow using selected markers: a case study. Genetics 149, 1383–1392 (2008). Reference 151 is as follows: Lenormand, T., Bourguet, D., Guillemaud, T. & Raymond, M.Tracking the evolution of insecticide resistance in the mosquito Culex pipiens. Nature400, 861–864 (1999). Reference 152 is as follows: Labb, P. et al. Forty years of erratic insecticide resistance evolution in the mosquito Culex pipiens.PLoS Genet. 3, 2190–2199 (2007). Reference 153 is as follows: Duron , O.et al. High Wolbachia density correlates with cost of infection for insecticide resistant Culex pipiens mosquitoes. Evolution60, 303–314 (2006). Additionally, Box 3 contained a typographical error: the time for the carbonaria morph of Biston betularia to reach 98% frequency was 47 years and not 7 years as stated in the Review. The authors apologize for these errors.
• Direct-access genetic testing: the view from Europe
  - Nat Rev Genet 13(1):70 (2012)
  Nature Reviews Genetics12, 670 (2011) Two sentences in the above article contained incorrect information. The sentence citing the study in reference 8 incorrectly stated that the study had been conducted through Facebook. The survey was in fact conducted online — but not through Facebook — so the sentence should have read "An online survey of >1,000 DTC customers in the United States found that most were satisfied with the testing experience and found their test results easy to understand". Additionally, the sentence citing the survey conducted in reference 11 incorrectly stated that few respondents were willing to pay for direct-to-consumer (DTC) genetic testing. In fact, this study did not look specifically at DTC testing. The authors of the study concluded that few participants were willing to pay more than 500 Canadian dollars for genetic testing, so the sentence should have read "By contrast, a recent Canadian survey indicated that few respondents were willing to pay more than 500 Canadian dollars for genetic testing". The article has been corrected online. The authors apologize for these errors.
• Regulatory RNA: Layer by layer
  - Nat Rev Genet 13(1):70 (2012)
  Nature Reviews Genetics12, 804 (2011) In the above article, the name of an author was misspelt in two places in the text and should have been Sumazin. This has been corrected online. The editors apologize for this error.