Variability in the incidence of miRNAs and genes in fragile sites and the role of repeats and CpG islands in the distribution of genetic material.

BACKGROUND: Chromosomal fragile sites are heritable specific loci especially prone to breakage. Some of them are associated with human genetic disorders and several studies have demonstrated their importance in genome instability in cancer. MicroRNAs (miRNAs) are small non-coding RNAs responsible of post-transcriptional gene regulation and their involvement in several diseases such as cancer has been widely demonstrated. The altered expression of miRNAs is sometimes due to chromosomal rearrangements and epigenetic events, thus it is essential to study miRNAs in the context of their genomic locations, in order to find significant correlations between their aberrant expression and the phenotype. PRINCIPAL FINDINGS: Here we use statistical models to study the incidence of human miRNA genes on fragile sites and their association with cancer-specific translocation breakpoints, repetitive elements, and CpG islands. Our results show that, on average, fragile sites are denser in miRNAs and also in protein coding genes. However, the distribution of miRNAs and protein coding genes in fragile versus non-fragile sites depends on chromosome. We find also a positive correlation between fragility and repeats, and between miRNAs and CpG islands. CONCLUSION: Our results show that the relationship between site fragility and miRNA density is far more complex than previously thought. For example, we find that protein coding genes seem to be following similar patterns as miRNAs, if considered their overall distribution. However, once we allow for differences at the chromosome level in our statistical analysis, we find that distribution of miRNA and protein coding genes in fragile sites is very different from that of miRNA. This is a novel result that we believe may help discover new potential correlations between the localization of miRNAs and their crucial role in biological processes and in the development of diseases.

Two years and 196 million pounds later: where is Choose and Book?

BACKGROUND AND OBJECTIVES: Introduced in 2004, Choose and Book was one of the National Programme for Information Technology's vanguard initiatives. It was to transform the old booking system by combining, for the first time, electronic booking with patient choice of their first hospital appointment. However, doctors' use of the system has been reported as being persistently low. This study, carried out in London, endeavoured to explore doctor's views about the system and to see how far it has progressed. METHOD: A questionnaire was devised and administered via an email invitation, to doctors. It was sent to 1800 and completed by 105 hospital consultants and general practitioners. RESULTS: Most doctors thought that the concept of electronic booking itself was a good idea. The benefits that have been observed so far include an improvement in patient attendance at their appointments and the ability of doctors to track referrals. The biggest problems were described as an increased workload, technical problems and an uneven distribution of appointments between hospitals. In addition, most doctors thought that patient choice was a misguided concept in electronic booking and most reported that they were unsatisfied with Choose and Book overall. LIMITATIONS: The 6% response rate may make the results less likely to be representative of the whole survey population. The authors acknowledge this and have made recommendations as to how to more comprehensively test the objectives of this study, in future. CONCLUSION: In general, Choose and Book is still poorly perceived by doctors - particularly with respect to technical problems. There is still some support for the concept of electronic booking; however the patient choice element faces more resistance. Additional research is needed on this topic to further investigate the use of electronic systems in the health service.