ORCID Profile
0000-0003-3602-5704
Current Organisation
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 29-04-2014
DOI: 10.1038/NCOMMS4756
Abstract: Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 lification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal ersity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater ersity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2020
Publisher: Wiley
Date: 30-04-2018
DOI: 10.1002/PATH.5081
Publisher: Elsevier BV
Date: 06-2016
Publisher: Wiley
Date: 19-08-2016
DOI: 10.1002/AJMG.A.37755
Publisher: Springer Science and Business Media LLC
Date: 20-04-2020
DOI: 10.1038/S42003-020-0885-5
Abstract: Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-02-2019
Publisher: Cold Spring Harbor Laboratory
Date: 29-12-2021
DOI: 10.1101/2021.12.28.21267792
Abstract: The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts. We convened a panel of clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups. We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight ex les of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for these variants. These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 26-06-2014
DOI: 10.1038/NCOMMS5264
Publisher: Springer Science and Business Media LLC
Date: 07-2007
DOI: 10.1038/NBT0707-739
Publisher: Oxford University Press (OUP)
Date: 20-08-2015
DOI: 10.1093/HMG/DDV331
Publisher: Oxford University Press (OUP)
Date: 25-01-2014
DOI: 10.1093/HMG/DDU030
Publisher: Wiley
Date: 16-05-2014
DOI: 10.1111/BJH.12910
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 11-07-2014
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1038/MI.2017.74
Publisher: Elsevier BV
Date: 06-2019
Publisher: Oxford University Press (OUP)
Date: 20-09-2013
DOI: 10.1093/BRAIN/AWT249
Abstract: Periventricular nodular heterotopia is caused by defective neuronal migration that results in heterotopic neuronal nodules lining the lateral ventricles. Mutations in filamin A (FLNA) or ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) cause periventricular nodular heterotopia, but most patients with this malformation do not have a known aetiology. Using comparative genomic hybridization, we identified 12 patients with developmental brain abnormalities, variably combining periventricular nodular heterotopia, corpus callosum dysgenesis, colpocephaly, cerebellar hypoplasia and polymicrogyria, harbouring a common 1.2 Mb minimal critical deletion in 6q27. These anatomic features were mainly associated with epilepsy, ataxia and cognitive impairment. Using whole exome sequencing in 14 patients with isolated periventricular nodular heterotopia but no copy number variants, we identified one patient with periventricular nodular heterotopia, developmental delay and epilepsy and a de novo missense mutation in the chromosome 6 open reading frame 70 (C6orf70) gene, mapping in the minimal critical deleted region. Using immunohistochemistry and western blots, we demonstrated that in human cell lines, C6orf70 shows primarily a cytoplasmic vesicular puncta-like distribution and that the mutation affects its stability and subcellular distribution. We also performed in utero silencing of C6orf70 and of Phf10 and Dll1, the two additional genes mapping in the 6q27 minimal critical deleted region that are expressed in human and rodent brain. Silencing of C6orf70 in the developing rat neocortex produced periventricular nodular heterotopia that was rescued by concomitant expression of wild-type human C6orf70 protein. Silencing of the contiguous Phf10 or Dll1 genes only produced slightly delayed migration but not periventricular nodular heterotopia. The complex brain phenotype observed in the 6q terminal deletion syndrome likely results from the combined haploinsufficiency of contiguous genes mapping to a small 1.2 Mb region. Our data suggest that, of the genes within this minimal critical region, C6orf70 plays a major role in the control of neuronal migration and its haploinsufficiency or mutation causes periventricular nodular heterotopia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-06-2016
Publisher: Elsevier BV
Date: 2020
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1038/GIM.2016.90
Publisher: Springer Science and Business Media LLC
Date: 10-10-2014
DOI: 10.1038/NCOMMS5809
Publisher: Springer Science and Business Media LLC
Date: 18-05-2201
DOI: 10.1038/NG.3304
Publisher: Springer Science and Business Media LLC
Date: 15-10-1999
Publisher: Springer Science and Business Media LLC
Date: 23-12-2012
DOI: 10.1038/NG.2503
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jenny Taylor.