Hot off the presses! Dec 01 Trends Genet

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Latest Articles Include:

• Editorial Board
  - Trends Genet 25(12):i (2009)
  
• Monoallelic expression and tissue specificity are associated with high crossover rates
  Necsulea A Sémon M Duret L Hurst LD - Trends Genet 25(12):519-522 (2009)
  What determines the recombination rate of a gene? Following the observation that, in humans, imprinted genes have unusually high recombination levels, we ask whether increased recombination is seen for other monoallelically expressed genes and, more generally, how transcriptional properties relate to recombination. We find that monoallelically expressed genes do have high crossover rates and discover a striking negative correlation between within-gene crossover rate and expression breadth. We hypothesise that these findings are possibly symptomatic of a more general, adverse relationship between recombination and transcription in the human genome.
• Increased rate of human mutations where DNA and RNA polymerases collide
  Jørgensen FG Schierup MH - Trends Genet 25(12):523-527 (2009)
  Gene density and orientation of genes in eukaryotes seem to be correlated with the replication origin and the mutation rate is greater in late replicating regions; however, the reason for these patterns is unknown. Here, we investigate predicted replication origins in the human genome and find that levels of polymorphism as well as divergence from the chimpanzee genome are greater in genes transcribed on the lagging strand than those on the leading strand. This might be caused by interference between RNA and DNA polymerases, and avoidance of collisions between these enzymes might be an evolutionary force shaping gene orientation and density surrounding replication start sites. Physical constraints might have a larger influence on genome evolution than previously thought.
• Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders
  Sebat J Levy DL McCarthy SE - Trends Genet 25(12):528-535 (2009)
  Recent studies have established an important role for rare genomic deletions and duplications in the etiology of schizophrenia. This research suggests that the genetic architecture of neuropsychiatric disorders includes a constellation of rare mutations in many different genes. Mutations that confer substantial risk for schizophrenia have been identified at several loci, most of which have also been implicated in other neurodevelopmental disorders, including autism. Genetic heterogeneity is a characteristic of schizophrenia; conversely, phenotypic heterogeneity is a characteristic of all schizophrenia-associated mutations. Both kinds of heterogeneity probably reflect the complexity of neurodevelopment. Research strategies must account for both genetic and clinical heterogeneity to identify the genes and pathways crucial for the development of neuropsychiatric disorders.
• Copy-number variants in neurodevelopmental disorders: promises and challenges
  Merikangas AK Corvin AP Gallagher L - Trends Genet 25(12):536-544 (2009)
  Copy-number variation (CNV) is the most prevalent type of structural variation in the human genome. There is emerging evidence that copy-number variants (CNVs) provide a new vista on understanding susceptibility to neuropsychiatric disorders. Some challenges in the interpretation of current CNV studies include the use of overlapping samples, differing phenotypic definitions, an absence of population norms for CNVs and a lack of consensus in methods for CNV detection and analysis. Here, we review current CNV association study methods and results in autism spectrum disorders (ASD) and schizophrenia, and provide suggestions for design approaches to future studies that might maximize the translation of this work to etiological understanding.
• Double duty for nuclear proteins – the price of more open forms of mitosis
  De Souza CP Osmani SA - Trends Genet 25(12):545-554 (2009)
  During cell division, eukaryotic cells pass on their genetic material to the next generation by undergoing mitosis, which segregates their chromosomes. During mitosis, the nuclear envelope, nuclear pore complexes and nucleolus must also be segregated. Cells achieve this in a range of different forms of mitosis, from closed, in which these nuclear structures remain intact, to open, in which these nuclear structures are disassembled. In between lies a smorgasbord of intermediate forms of mitosis, displaying varying degrees of nuclear disassembly. Gathering evidence is revealing links between the extent of nuclear disassembly and the evolution of new roles for nuclear proteins during mitosis. We propose that proteins with such double duties help coordinate reassembly of the nucleus with chromosomal segregation.
• Tubulin-related cortical dysgeneses: microtubule dysfunction underlying neuronal migration defects
  Jaglin XH Chelly J - Trends Genet 25(12):555-566 (2009)
  The fine tuning of proliferation and neurogenesis, neuronal migration and differentiation and connectivity underlies the proper development of the cerebral cortex. Mutations in genes involved in these processes are responsible for neurodevelopmental disorders, such as cortical dysgeneses, which are usually associated with severe mental retardation and epilepsy. Over the past few years, the importance of cytoskeleton components in cellular processes crucial for cortical development has emerged from a body of functional data. This was reinforced by the association of mutations in the LIS1 and DCX genes, which both encode proteins involved in microtubule (MT) homeostasis, with cerebral cortex developmental disorders. The recent discovery of patients with lissencephaly and bilateral asymmetrical polymicrogyria (PMG) carrying mutations in the α- and β-tubulin-encoding genes TUBA1A and TUBB2B further supports this view, and also raises interesting questions about the speci! fic roles played by certain tubulin isotypes during the development of the cortex.