Alexander Stuckey
A5047253474- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
- Genetic and Kidney Cyst Diseases
- Genomic variations and chromosomal abnormalities
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
- Genetic Syndromes and Imprinting
- Genetic Associations and Epidemiology
- interferon and immune responses
- Liver Disease Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Single-cell and spatial transcriptomics
- RNA regulation and disease
- Urological Disorders and Treatments
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Renal and related cancers
- Ion Transport and Channel Regulation
- Chronic Lymphocytic Leukemia Research
Genomics England
2020-2025
Queen Mary University of London
2021-2024
KTH Royal Institute of Technology
2017-2021
Science for Life Laboratory
2017-2021
Jackson Laboratory
2021
University of Auckland
2015-2017
Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage and repair processes that have arisen in each patient's cancer. We performed signature analyses on 12,222 WGS tumor-normal matched pairs, from patients recruited via the UK National Health Service. contrasted our results to two independent datasets, International Cancer Genome Consortium (ICGC) Hartwig Foundation, involving 18,640 cancers total. Our add 40...
Long QT syndrome (LQTS) is an autosomal dominant condition predisposing to sudden death from malignant arrhythmia. Genetic testing identifies many missense single nucleotide variants of uncertain pathogenicity. Establishing genetic pathogenicity essential prerequisite family cascade screening. Many laboratories use in silico prediction tools, either alone or combination, metaservers, order predict pathogenicity; however, their accuracy the context LQTS unknown. We evaluated five programs and...
The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but preferentially protected transcription-coupled repair
Host genetics is a key determinant of COVID-19 outcomes. Previously, the Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with However, largest impact on outcomes are expected be rare in population. Hence, studying may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome whole-genome sequencing from 21 cohorts across 12 countries performed...
Abstract The value of genome-wide over targeted driver analyses for predicting clinical outcomes cancer patients is debated. Here, we report the whole-genome sequencing 485 chronic lymphocytic leukemia enrolled in trials as part United Kingdom’s 100,000 Genomes Project. We identify an extended catalog recurrent coding and noncoding genetic mutations that represents a source future studies provide most complete high-resolution map structural variants, copy number changes global genome...
Dravet syndrome is an archetypal rare severe epilepsy, considered 'monogenic', typically caused by loss-of-function SCN1A variants. Despite a recognizable core phenotype, its marked phenotypic heterogeneity incompletely explained differences in the causal variant or clinical factors. In 34 adults with SCN1A-related syndrome, we show additional genomic variation beyond contributes to phenotype and diversity, excess of variants epilepsy-related genes as set examples blended phenotypes,...
Alport syndrome is the commonest inherited kidney disease and nearly half pathogenic variants in COL4A3-COL4A5 genes that cause result Gly substitutions. This study examined molecular characteristics of substitutions determine severity clinical features. Pathogenic COL4A5 affecting Leiden Open Variation Database males with X-linked were correlated age at failure (n = 157) hearing loss diagnosis 80). Heterozygous COL4A3 COL4A4 304) autosomal dominant risk haematuria UK 100,000 Genomes...
CAG repeat expansions in exon 1 of the AR gene on X chromosome cause spinal and bulbar muscular atrophy, a male-specific progressive neuromuscular disorder associated with variety extra-neurological symptoms. The disease has reported male prevalence approximately 1:30 000 or less, but expansion frequency is unknown. We established pipeline, which combines use ExpansionHunter tool visual validation, to detect whole-genome sequencing data, benchmarked it fragment PCR sizing, applied 74 277...
We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving phasing switch error rate of 0.18% for European samples and imputation quality r
Understanding the genetic basis of gene expression can shed light on regulatory mechanisms underlying complex traits and diseases. Single-cell resolved measures RNA levels single-cell quantitative trait loci (sc-eQTLs) have revealed regulation that drives sub-tissue cell states types across diverse human tissues. Here, we describe first phase TenK10K, largest-to-date dataset matched whole-genome sequencing (WGS) RNA-sequencing (scRNA-seq). We leverage scRNA-seq data from over 5 million cells...
PurposeDetermining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD).MethodsGenome and exome sequencing were performed for five unrelated cases IRD with no identified variant. In vitro assays developed to validate (fibroblast assay, induced pluripotent stem cell [iPSC] derived organoids, a dynein motility assay).ResultsFour novel (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) one previously reported variant (V5,...
Abstract Background Cancer genome sequencing enables accurate classification of tumours and tumour subtypes. However, prediction performance is still limited using exome-only for types with low somatic mutation burden such as many paediatric tumours. Moreover, the ability to leverage deep representation learning in discovery entities remains unknown. Methods We introduce here Mutation-Attention (MuAt), a neural network learn representations simple complex alterations In contrast previous...
Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by pathogenic variants in the PKD1 and PKD2 genes. Although type of ADPKD variant can influence severity, rare, hypomorphic have also been reported to modify severity or cause biallelic ADPKD. This study examines whether additional, potentially protein-altering, non-pathogenic contribute phenotypic outcomes. We investigated prevalence protein-altering patients with PKD1-associated The association between outcomes,...
Abstract Background Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral and its relationship with clinicopathological variables not yet characterized in detail. We hypothesized that variation microbial abundance, alpha diversity, composition is related characteristics. Methods Metagenomic analysis of 529 GC samples was performed, including whole exome sequencing data Cancer Genome Atlas (TCGA)...
PurposeThis study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants.MethodsIndividuals protein altering variants in were identified through exome and genome sequencing international data sharing. Deep clinical phenotyping was undertaken by referring clinicians. Blood DNA methylation assessed using Infinium MethylationEPIC array. The expression pattern developing human brain defined RNAscope.ResultsWe reported 38 new patients variants....
Urinary stone disease (USD) is a major health burden affecting over 10% of the United Kingdom population. While associated with lifestyle, genetic factors also strongly contribute. Common variants at multiple loci from genome-wide association studies account for 5% estimated 45% heritability disorder. Here, we investigated extent to which rare variation contributes unexplained USD. Among participants 100,000-genome project, 374 unrelated individuals were identified and assigned diagnostic...
Abstract Improvements in functional genomic annotation have led to a critical mass of neurogenetic discoveries. This is exemplified hereditary ataxia, heterogeneous group disorders characterised by incoordination from cerebellar dysfunction. Associated pathogenic variants more than 300 genes been described, leading detailed genetic classification partitioned age-of-onset. Despite these advances, up 75% patients with ataxia remain molecularly undiagnosed even following whole genome...
Abstract Cardiomyopathy has variable penetrance. We analyzed age and sex-related genetic differences in 1,397 cardiomyopathy patients (Ontario, UK) with whole genome sequencing. Pediatric cases (n = 471) harbored more deleterious protein-coding variants Tier 1 genes compared to adults 926) (34.6% vs 25.9% respectively, p 0.0015), variant enrichment constrained coding regions. had a higher burden of sarcomere lower channelopathy gene adults. Specifically, pediatric MYH7 MYL3 hypertrophic...
As the only endemic member in New Zealand of ancient conifer family, Araucariaceae, Agathis australis is an ideal species to study putatively long-evolved mycorrhizal symbioses. However, little known about A. root and nodular arbuscular fungi (AMF), how colonisation occurs. We used light, scanning transmission electron microscopy characterise colonisation, 454-sequencing identify AMF associated with roots nodules. interpreted results terms edaphic characteristics australis-influenced...