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How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders(More)
The MAPT H1c haplotype is a risk factor for the neurodegenerative tauopathies progressive supranuclear palsy (PSP) and Alzheimer's disease. We hypothesise that the effect of the H1c haplotype relates to an increase in MAPT expression leading to an increase in tau neurofibrillary tangle deposition. We have evaluated the effect of the MAPT H1c haplotype on(More)
Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 haplotype of MAPT, the gene encoding tau, is the major risk factor in PSP. A 3-repeat and 4-repeat (4R) tau isoform ratio imbalance has been strongly implicated as a cause(More)
Spinocerebellar ataxias (SCAs) are a group of clinically and genetically heterogeneous neurological diseases. The expansion of unstable microsatellite repeats has been identified as the underlying pathogenic cause of 10 subtypes of autosomal dominant SCAs. The aetiology of sporadic SCA is unknown. The aim of this study was to investigate the effect of large(More)
Evolutionary theories are themselves subject to evolution. Clonal evolution - the model that describes the initiation and progression of cancer - is entering a period of profound change, brought about largely by technological developments in genome analysis. A flurry of recent publications, using modern mathematical and bioinformatics techniques, have(More)
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