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Molecular testing for the BCR-ABL1 fusion gene by real time quantitative polymerase chain reaction (RT-qPCR) is the most sensitive routine approach for monitoring the response to therapy of patients with chronic myeloid leukaemia. In the context of tyrosine kinase inhibitor (TKI) therapy, the technique is most appropriate for patients who have achieved complete cytogenetic remission and can be used to define specific therapeutic milestones. To achieve this effectively, standardization of the laboratory procedures and the interpretation of results are essential. We present here consensus best practice guidelines for RT-qPCR testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 21 testing laboratories in the United Kingdom and Ireland in accordance with the procedures of the UK Clinical Molecular Genetics Society.

Spinal muscular atrophy is a common neuromuscular disorder caused by mutations in the survival motor neuron (SMN) gene. In mammals, SMN is tightly associated with Gemin2. To gain further insight into the functions of SMN and Gemin2, we have cloned and sequenced smi-1 (Survival of Motor neuron-Interacting protein 1), a C. elegans homologue of the human Gemin2 gene. We show that the SMI-1 expression pattern and RNA interference phenotype show considerable overlap with that previously reported for SMN-1. Finally, we demonstrate that the SMN-1 and SMI-1 proteins directly interact. Having demonstrated the utility of the C. elegans genetic model for investigating genes encoding SMN-interacting proteins, we have undertaken a yeast two-hybrid screen of a C. elegans cDNA library to identify novel proteins that interact with SMN-1. We show the direct interaction of SMN-1 with nine novel proteins, several of which may be involved in RNA metabolism.

Introduction Gastric smooth muscle layers are electrically excited by slow waves. In the normal stomach, slow waves propagate longitudinally in ring wavefronts from the upper corpus to the distal antrum. Circumferential propagation does not appear to occur, likely because there is no excitable tissue available circumferentially in these rings. However, rapid circumferential propagation has been observed in isolated gastric tissues and during gastric pacing. In this study, the propagation profiles of slow wave behaviors in diabetic gastroparesis were defined at high resolution (HR). The hypothesis was that circumferential propagation occurs during dysrhythmia, presenting a novel marker of gastric electrical dysfunction. Methods HR (multi-electrode) mapping was performed in 7 patients with diabetic gastroparesis undergoing laparotomy for stimulator implantation. Anterior serosal recordings were taken using flexible PCB arrays (256 electrodes; 4 mm spacing; 36cm2), and activation mapping was performed. Velocity fields were calculated using a finite difference approach incorporating a Gaussian filter smoothing function. Amplitudes were calculated using a peak-trough detection algorithm. Longitudinal and circumferential propagation data from corpus recordings were compared with Student's t-test. Means±SEM are reported. Results Atypical or dysrhythmic propagation was observed in 6/7 patients, including incomplete conduction block, complete block with escape, ectopic pacemaking in the corpus and antral tachygastria (freq range: 2.7-4.2 cpm). Circumferential propagation was associated with all of these events (circumferential velocity 6.6 ± 0.9 mm/s vs longitudinal velocity 2.9 ± 0.2 mm/s; p

Background Down syndrome (DS), caused by trisomy of human chromosome 21 (HSA21), is the most common genetic birth defect. Congenital heart defects (CHD) are seen in 40% of DS children, and >50% of all atrioventricular canal defects in infancy are caused by trisomy 21, but the causative genes remain unknown. Results Here we show that aberrant adhesion and proliferation of DS cells can be reproduced using a transchromosomic model of DS (mouse fibroblasts bearing supernumerary HSA21). We also demonstrate a deacrease of cell migration in transchromosomic cells independently of their adhesion properties. We show that cell-autonomous proteome response to the presence of Collagen VI in extracellular matrix is strongly affected by trisomy 21. Conclusion This set of experiments establishes a new model system for genetic dissection of the specific HSA21 gene-overdose contributions to aberrant cell migration, adhesion, proliferation and specific proteome response to collagen VI, cellular phenotypes linked to the pathogenesis of CHD.