Hot off the presses! May 01 TRENDS GENET

The May 01 issue of the TRENDS GENET is now up on Pubget (About TRENDS 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:

• Editorial Board
  - TRENDS GENET 27(5):i (2011)
  
• What are the genomic drivers of the rapid evolution of PRDM9?
  - TRENDS GENET 27(5):165-171 (2011)
  Mammalian Prdm9 has been proposed to be a key determinant of the positioning of chromosome double-strand breaks during meiosis, a contributor to speciation processes, and the most rapidly evolving gene in human, and other animal, genomes. Prdm9 genes often exhibit substantial variation in their numbers of encoded zinc fingers (ZFs), not only between closely related species but also among individuals of a species. The near-identity of these ZF sequences appears to render them very unstable in copy number. The rare sequence differences, however, cluster within ZF sites that determine the DNA-binding specificity of PRDM9, and these substitutions are frequently positively selected. Here, possible drivers of the rapid evolution of Prdm9 are discussed, including selection for efficient pairing of homologous chromosomes or for recombination of deleterious linked alleles, and selection against depletion of recombination hotspots or against disease-associated genome rearrangeme! nt.
• Chromatin and heritability: how epigenetic studies can complement genetic approaches
  - TRENDS GENET 27(5):172-176 (2011)
  Despite the success in using genome-wide association studies to identify many loci associated with human disease, there are several gaps in understanding of how common genetic diseases are manifested. Epigenetic studies, which focus on DNA and chromatin modifications, have the potential to complement genetic approaches and provide more insight into mechanism, environmental effects and modes of inheritance, including the potential for non-DNA-based heritability. However, there are considerable challenges in designing and interpreting epigenetic studies associated with disease. Here, I review recent studies focused on individual variation in chromatin, and outline how epigenome-based studies can be used to complement genetic studies. In particular, I see more benefit to epigenetic studies being performed in the context of genetic studies, rather than as separate investigations.
• Heterochromatin establishment in the context of genome-wide epigenetic reprogramming
  - TRENDS GENET 27(5):177-185 (2011)
  Heterochromatin at pericentric satellites, characterized by a specific chromatin signature and chromocenter organization, is of paramount importance for genome function. Re-establishment of this organization after fertilization takes place in the context of genome-wide epigenetic reprogramming. We review how the asymmetry in histone variants and post-translational modifications between paternal and maternal genomes and their respective pericentric heterochromatin domains evolve during early cleavage stages in mouse. We draw a parallel between these data and the burst of pericentric satellite transcription that occurs concomitantly with the dynamic reorganization of the pericentric domains into chromocenters in two-cell stage embryos. Based on this new angle, we propose that a crucial developmental transition at the two-cell stage allows chromocenter formation by involving non-coding satellite transcripts to trigger specific chromatin changes.
• Improving animal phylogenies with genomic data
  - TRENDS GENET 27(5):186-195 (2011)
  Since the first animal genomes were completely sequenced ten years ago, evolutionary biologists have attempted to use the encoded information to reconstruct different aspects of the earliest stages of animal evolution. One of the most important uses of genome sequences is to understand relationships between animal phyla. Despite the wealth of data available, ranging from primary sequence data to gene and genome structures, our lack of understanding of the modes of evolution of genomic characters means that using these data is fraught with potential difficulties, leading to errors in phylogeny reconstruction. Improved understanding of how different character types evolve, the use of this knowledge to develop more accurate models of evolution, and denser taxonomic sampling, are now minimizing the sources of error. The wealth of genomic data now being produced promises that a well-resolved tree of the animal phyla will be available in the near future.
• Genetic therapies for RNA mis-splicing diseases
  - TRENDS GENET 27(5):196-205 (2011)
  RNA mis-splicing diseases account for up to 15% of all inherited diseases, ranging from neurological to myogenic and metabolic disorders. With greatly increased genomic sequencing being performed for individual patients, the number of known mutations affecting splicing has risen to 50–60% of all disease-causing mutations. During the past 10 years, genetic therapy directed toward correction of RNA mis-splicing in disease has progressed from theoretical work in cultured cells to promising clinical trials. In this review, we discuss the use of antisense oligonucleotides to modify splicing as well as the principles and latest work in bifunctional RNA, trans-splicing and modification of U1 and U7 snRNA to target splice sites. The success of clinical trials for modifying splicing to treat Duchenne muscular dystrophy opens the door for the use of splicing modification for most of the mis-splicing diseases.