Letizia Vestito
A5064862558- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Gene expression and cancer classification
- Biomedical Text Mining and Ontologies
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Genomics and Phylogenetic Studies
- Congenital heart defects research
- Neurotransmitter Receptor Influence on Behavior
- Single-cell and spatial transcriptomics
- Amyotrophic Lateral Sclerosis Research
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Neurogenetic and Muscular Disorders Research
- Childhood Cancer Survivors' Quality of Life
- Neuropeptides and Animal Physiology
- Genetic factors in colorectal cancer
- Hearing, Cochlea, Tinnitus, Genetics
- Biotechnology and Related Fields
- Birth, Development, and Health
William Harvey Research Institute
2021-2025
Queen Mary University of London
2021-2025
University College London
2020-2025
Great Ormond Street Hospital
2022-2023
University of Wisconsin–Madison
2023
Babraham Institute
2020-2022
NIHR Great Ormond Street Hospital Biomedical Research Centre
2022
University of Birmingham
2021
National Institute for Health Research
2021
Institute of Child Health
2019
The U.K. 100,000 Genomes Project is in the process of investigating role genome sequencing patients with undiagnosed rare diseases after usual care and alignment this research health implementation National Health Service. Other parts project focus on cancer infection.
Abstract Up to 80% of rare disease patients remain undiagnosed after genomic sequencing 1 , with many probably involving pathogenic variants in yet be discovered disease–gene associations. To search for such associations, we developed a variant gene burden analytical framework Mendelian diseases, and applied it protein-coding from whole-genome 34,851 cases their family members recruited the 100,000 Genomes Project 2 . A total 141 new associations were identified, including five which...
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 Objective This study aims to describe the genetic landscape of syndromic and non-syndromic hearing loss (HL) in UK population using data from 100,000 Genomes Project (100kGP). Design Cohort Setting NHS England Participants 2,271 families with HL recruited 100kGP rare disease programme between 2013 2018. at least one Human Phenotype Ontology (HPO) term descendant “Hearing impairment” (HP:0000365) were included; this equated 5,488 individuals, comprising 2,762 affected individuals...
Abstract Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis and frontotemporal dementia, based on identification of likely pathogenic variants in patients from distinct dementia cohorts. By screening a multicentric French cohort 448 unrelated probands presenting cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent public databases predicted by multiple silico tools. In addition, burden analyses the 100 000...
Abstract Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) both humans and dogs. Studies implicating phenotypic consequences of mutations to be subcellular disruption autophagy lipid metabolism have been limited vitro investigation patient-derived dermal fibroblasts, laboratory engineered cell lines developmental analysis zebrafish morphants. homologues Snz ( Drosophila ) Mdm1 (yeast) also conducted, demonstrated an important biochemical role during...
RPH3A encodes a protein involved in the stabilization of GluN2A subunit N-methyl-D-aspartate (NMDA)-type glutamate receptors at cell surface, forming complex essential for synaptic plasticity and cognition. We investigated effect variants patients with neurodevelopmental disorders.By using trio-based exome sequencing, GeneMatcher, screening 100,000 Genomes Project data, we identified 6 heterozygous RPH3A. In silico vitro models, including rat hippocampal neuronal cultures, have been used to...
To discover rare disease-gene associations, we developed a gene burden analytical framework and applied it to rare, protein-coding variants from whole genome sequencing of 35,008 cases with diseases their family members recruited the 100,000 Genomes Project (100KGP). Following
Whole genome sequencing has transformed rare disease research; however, 50–80% of patients remain undiagnosed after such testing. Regular reanalysis can identify new diagnoses, especially in newly discovered disease-gene associations, but efficient tools are required to support clinical interpretation. Exomiser, a phenotype-driven variant prioritisation tool, fulfils this role; within the 100,000 Genomes Project (100kGP), diagnoses were identified 463 (2%) 24,015 unsolved previous analysis...
ABSTRACT Forebrain dopaminoceptive neurons play a key role in movement, action selection, motivation, and working memory. Their activity is dysregulated addiction, Parkinson’s disease other conditions. To characterize the diverse dopamine target neuronal populations, we compare translating mRNAs of dorsal striatum nucleus accumbens expressing D1 or D2 receptor prefrontal cortex receptor. We identify D1/D2 striatal dorso-ventral differences translational splicing landscapes, which establish...
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...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
Abstract Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) both humans and dogs. SCAR20 is understood to involve subcellular disruption autophagy lipid metabolism. Previously reported studies on phenotypic consequences of mutations have been limited vitro investigation patient-derived dermal fibroblasts, laboratory engineered cell lines developmental analysis zebrafish morphants. In addition, investigated biochemical roles homologues Snz ( Drosophila )...
Up to 60–74% of patients with hereditary ataxia (HA) remain undiagnosed even following whole genome sequencing. We leveraged publicly-available -omics data generate 299 genic features, capturing information about: gene structure/complexity; genetic variation; tissue-specific, cell-specific and tempo- rally-relevant expression/co-expression protein products. Using existing age-of-onset informa- tion, we categorised HA-linked genes as childhood-onset, adult-onset those overlapping both. By...
Abstract Animal models have long been used to study gene function and the impact of genetic mutations on phenotype. Through research efforts thousands groups, systematic curation published literature, high-throughput phenotyping screens, collective body knowledge for mouse now covers majority protein-coding genes. We here collected data over 53,000 with in 15,000 genomic markers characterized by more than 254,000 annotations using 9,000 distinct ontology terms. investigated dimensional...
Animal models have long been used to study gene function and the impact of genetic mutations on phenotype. Through research efforts thousands groups, systematic curation published literature high-throughput phenotyping screens, collective body knowledge for mouse now covers majority protein-coding genes. We here collected data over 53 000 with in 15 genomic markers characterized by more than 254 annotations using 9000 distinct ontology terms. investigated dimensional reduction embedding...