Hot off the presses! Aug 01 Nat Rev Genet

The Aug 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:

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  - Nat Rev Genet 12(8):517 (2011)
  
• Gene expression: Transcriptome to proteome and back to genome | PDF (471 KB)
  - Nat Rev Genet 12(8):518 (2011)
  Gene expression is routinely quantified by measuring mRNA levels. However, there is uncertainty about how closely levels of mRNAs relate to levels of their corresponding proteins — several papers suggest only a modest correlation.
• Small RNA: Coding repeats coordinate repression | PDF (253 KB)
  - Nat Rev Genet 12(8):519 (2011)
  Most characterized binding sites for microRNAs (miRNAs) lie in the 3′ UTRs of their target mRNAs. The few that have been found in ORFs or 5′ UTRs are generally thought to confer less effective mRNA repression, perhaps because the translation machinery displaces the miRNA silencing complex from these sites.
• Transcriptomics: Sense and antisense ability | PDF (200 KB)
  - Nat Rev Genet 12(8):519 (2011)
  Although the alternative splicing of some transcripts is known to be influenced by the expression of corresponding antisense transcripts, the extent of this phenomenon was unclear. New research suggests that splicing regulation by antisense transcripts may be remarkably common.
• Gene regulation: Together, for better | PDF (171 KB)
  - Nat Rev Genet 12(8):520 (2011)
  The growing number of sequenced genomes is showing that operons, far from being the exclusive domain of prokaryotes, also make up a surprisingly large portion of some eukaryotic genomes. What advantage could operons possibly have in eukaryotes, given that — unlike prokaryotes — they do not share gene sets by horizontal gene transfer?
• Human genomics: Known and unknown | PDF (345 KB)
  - Nat Rev Genet 12(8):520 (2011)
  The tidal waves of data from high-throughput sequencing enable new attempts to address vexing questions of inheritance and evolution. One of the most sought after insights has been a direct and accurate measure of the human mutation rate.
• Gene regulation | Therapy | Cancer genomics | Development | PDF (83 KB)
  - Nat Rev Genet 12(8):521 (2011)
  Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites Scharff, L. B.et al. PLoS Genet. 7, e1002155 (2011)
• Functional genomics: Degrees of similarity | PDF (264 KB)
  - Nat Rev Genet 12(8):522 (2011)
  A study has reversed the common but untested assumption that orthologous gene pairs are functionally more similar to each other than paralogous pairs are. This finding could influence the practice of using evolutionary relationships to infer function from sequence.
• Epigenomics: Reprogramming in transition | PDF (277 KB)
  - Nat Rev Genet 12(8):522 (2011)
  Reprogramming of the mammalian epigenome has been the subject of intense scrutiny in the contexts of germ cells and stem cells. Now, a new study reveals that epigenome reprogramming is also a crucial feature of epithelial-to-mesenchymal transition (EMT) — an example of extreme cellular plasticity that occurs during normal development and during transformation of cells to malignancy.
• New approaches to disease mapping in admixed populations
  - Nat Rev Genet 12(8):523 (2011)
  Admixed populations such as African Americans and Hispanic Americans are often medically underserved and bear a disproportionately high burden of disease. Owing to the diversity of their genomes, these populations have both advantages and disadvantages for genetic studies of complex phenotypes. Advances in statistical methodologies that can infer genetic contributions from ancestral populations may yield new insights into the aetiology of disease and may contribute to the applicability of genomic medicine to these admixed population groups.
• Epigenome-wide association studies for common human diseases
  - Nat Rev Genet 12(8):529 (2011)
  Despite the success of genome-wide association studies (GWASs) in identifying loci associated with common diseases, a substantial proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation. Such epigenome-wide association studies (EWASs) present novel opportunities but also create new challenges that are not encountered in GWASs. We discuss EWAS design, cohort and sample selections, statistical significance and power, confounding factors and follow-up studies. We also discuss how integration of EWASs with GWASs can help to dissect complex GWAS haplotypes for functional analysis.
• Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation
  - Nat Rev Genet 12(8):542 (2011)
  In female mammals, one of the two X chromosomes is silenced for dosage compensation between the sexes. X-chromosome inactivation is initiated in early embryogenesis by the Xist RNA that localizes to the inactive X chromosome. During development, the inactive X chromosome is further modified, a specialized form of facultative heterochromatin is formed and gene repression becomes stable and independent of Xist in somatic cells. The recent identification of several factors involved in this process has provided insights into the mechanism of Xist localization and gene silencing. The emerging picture is complex and suggests that chromosome-wide silencing can be partitioned into several steps, the molecular components of which are starting to be defined.
• Determinants and dynamics of genome accessibility
  - Nat Rev Genet 12(8):554 (2011)
  In eukaryotes, all DNA-templated reactions occur in the context of chromatin. Nucleosome packaging inherently restricts DNA accessibility for regulatory proteins but also provides an opportunity to regulate DNA-based processes through modulating nucleosome positions and local chromatin structure. Recent advances in genome-scale methods are yielding increasingly detailed profiles of the genomic distribution of nucleosomes, their modifications and their modifiers. The picture now emerging is one in which the dynamic control of genome accessibility is governed by contributions from DNA sequence, ATP-dependent chromatin remodelling and nucleosome modifications. Here we discuss the interplay of these processes by reviewing our current understanding of how chromatin access contributes to the regulation of transcription, replication and repair.
• Genomic imprinting: the emergence of an epigenetic paradigm
  - Nat Rev Genet 12(8):565 (2011)
  The emerging awareness of the contribution of epigenetic processes to genome function in health and disease is underpinned by decades of research in model systems. In particular, many principles of the epigenetic control of genome function have been uncovered by studies of genomic imprinting. The phenomenon of genomic imprinting, which results in some genes being expressed in a parental--origin-specific manner, is essential for normal mammalian growth and development and exemplifies the regulatory influences of DNA methylation, chromatin structure and non-coding RNA. Setting seminal discoveries in this field alongside recent progress and remaining questions shows how the study of imprinting continues to enhance our understanding of the epigenetic control of genome function in other contexts.
• The future of model organisms in human disease research
  - Nat Rev Genet 12(8):575 (2011)
  Model organisms have played a huge part in the history of studies of human genetic disease, both in identifying disease genes and characterizing their normal and abnormal functions. But is the importance of model organisms diminishing? The direct discovery of disease genes and variants in humans has been revolutionized, first by genome-wide association studies and now by whole-genome sequencing. Not only is it now much easier to directly identify potential disease genes in humans, but the genetic architecture that is being revealed in many cases is hard to replicate in model organisms. Furthermore, disease modelling can be done with increasing effectiveness using human cells. Where does this leave non-human models of disease?