In a paper published online in advance in Genome Research this week, the European Molecular Biology Laboratory's Jan Korbel et al. present evidence to "suggest that association-studies can gain in resolution and power by including fine-scale CNV information, such as those obtained from population-scale sequencing." For its study, Korbel's team set out to evaluate the impact of CNVs on gene expression "by relating copy-number genotypes to transcriptome sequencing data," finding an "enrichment of large duplications and deletions, including large intergenic CNVs, relative to the entire set of expression-associated CNVs."
Investigators at F. Hoffmann-La Roche AG's Pharmaceutical Research and Early Development facility in Switzerland, along with their colleagues at Roche NimbleGen in the US, present their genome-based assessment of the long-tailed macaque Macaca fascicularis as a model for human drug safety evaluation. Using a whole-genome shotgun approach, the Roche team sequenced the genome of a female M. fascicularis. By applying a template-switch strategy on both macaque and human sequence data, the team performed a homology-based annotation, identifying 17,387 orthologs of human protein-coding genes in the M. fascicularis draft genome they generated.
An international team led by researchers at the University of Geneva characterizes the epigenetic changes that accompany X-chromosome inactivation, or XCI, in a Genome Research paper published online in advance this week. "We observed that XCI is accompanied by changes in DNA methylation specifically at CpG islands," the authors write, adding that "both intra- and inter-genic CGIs undergo epigenetic modification, with the biggest increase in methylation occurring at the promoters of genes silenced by XCI."
Elsewhere in Genome Research, a team led by investigators at the Netherlands Cancer Institute presents shear-splink: an approach that employs random fragmentation of genomic DNA to reduce the occurrence of unwanted amplification biases "for the semi-quantitative high-throughput analysis of insertional mutations." The team adds that shear-splink also enables the assessment of "clonality of individual insertions by determining the number of unique ligation points between the adapter and genomic DNA," thus allowing a "semi-quantitative measure of the relative clonality of individual insertions within heterogeneous samples and permits discrimination between — near — clonal insertions and those insertions that occur in single, or just a few cells, within the tumor."