Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants

Background We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080). We then compared our new data to previous structural variant mutagenesis studies involving the Xq22 region of the human genome. The aggregate data from 159 sequenced join-points (discontinuous sequences in the reference genome that are joined during the rearrangement process) were studied. Analysis of these data from 150 individuals enabled the spectrum and relative distribution of the underlying genomic mutational signatures to be delineated. Methods Genomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array or clinical chromosomal microarray analysis and breakpoint junction sequence analysis. Results High-density customized array showed that the majority of cases (33/50; ~ 66%) present with single duplications, although complex genomic rearrangements (CGRs) are also frequent (17/50; ~ 34%). Breakpoint mapping to nucleotide resolution revealed further previously unknown structural and sequence complexities, even in single duplications. Meta-analysis of all studied rearrangements that occur at the PLP1 locus showed that single duplications were found in ~ 54% of individuals and that, among all CGR cases, triplication flanked by duplications is the most frequent CGR array CGH pattern observed. Importantly, in ~ 32% of join-points, there is evidence for a mutational signature of microhomeology (highly similar yet imperfect sequence matches). Conclusions These data reveal a high frequency of CGRs at the PLP1 locus and support the assertion that replication-based mechanisms are prominent contributors to the formation of CGRs at Xq22. We propose that microhomeology can facilitate template switching, by stabilizing strand annealing of the primer using W-C base complementarity, and is a mutational signature for replicative repair.

A Resource Discovery Mechanism on Cloud Computing System

Cloud Computing is an efficient way to resolve the resource sharing and cooperative work in distributed environments. Considering the disadvantages of traditional Scheduling method and the characteristics of Cloud Computing System, a resource discovery mechanism has been designed and implemented. Firstly, a calculation method based on each join points’ loading has been proposed, providing the Formula of method. Secondly, a comprehensive service resource distribution method has been designed and implemented in consideration of respective service resource counts, each join points’ performance and current loading distribution. Finally, the result of the experiment indicates that the scheduling system can improve the efficiency of dispatching service resource and the utilization ratio of distributed service resource on Cloud Computing System.

A Research on Join-Points-Capture in Program Scope and Process-Control by AspectJ

This paper achieves the capture of Java-program-scope and joint-point-information based on process-control with AspectJ. This information includes: all joint points in particular classes, packages, and methods. It also includes all joint-points from beginning in program control-flow and those in which initial one is not included.