Sarah J. Beecroft
A5026308135- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Mitochondrial Function and Pathology
- Genetic factors in colorectal cancer
- Glycogen Storage Diseases and Myoclonus
- Cellular Mechanics and Interactions
- Nuclear Structure and Function
- Congenital Diaphragmatic Hernia Studies
- Heat shock proteins research
- DNA Repair Mechanisms
- Bacteriophages and microbial interactions
- Connective tissue disorders research
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Neonatal Respiratory Health Research
- Plant Virus Research Studies
- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
Pawsey Supercomputing Research Centre
2022-2025
Harry Perkins Institute of Medical Research
2015-2024
University of Toledo
2024
Queen Elizabeth II Medical Centre
2017-2023
The University of Western Australia
2016-2023
The University of Sydney
2021
Children's Hospital at Westmead
2021
Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) major late onset ataxia. Here we describe full spectrum disease phenotype our first 100 genetically confirmed carriers expansions RFC1 identify sensory neuropathy common feature all cases to date. All...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause CANVAS. We screened an Asian-Pacific cohort for CANVAS novel repeat motif, (ACAGG)exp, three affected individuals. This motif associated with additional clinical features including fasciculations elevated serum creatine kinase. These have not previously been described individuals...
Expansions of short tandem repeats (STRs) cause many rare diseases. Expansion detection is challenging with short-read DNA sequencing data since supporting reads are often mapped incorrectly. Detection particularly difficult for "novel" STRs, which include new motifs at known loci or STRs absent from the reference genome. We developed STRling to efficiently count k-mers recover informative and call expansions novel STR loci. sensitive disease loci, has a low false discovery rate, resolves...
Abstract RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous terms of age onset, disease progression and phenotype. We investigated the role size influencing clinical variables disease. also assessed presence meiotic somatic instability repeat. In this study, we identified 553 patients carrying expansions measured 392 cases. Pearson’s coefficient was calculated to assess correlation between at onset. A Cox model with robust cluster standard errors adopted...
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited manifesting with ptosis, dysphagia and distal weakness. Pathologically it characterised by rimmed vacuoles intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified OPDM individuals Asian populations. None of these have been found affected non-Asian ancestry. this study we describe the identification expansions ABCD3 , ranging from 118 to 694 repeats, 35 across...
Abstract Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative disease onset in mid- to late adulthood. The genetic basis for large proportion of Caucasian patients was shown be the biallelic expansion pentanucleotide (AAGGG)n repeat RFC1. Here, we describe first instance CANVAS testing New Zealand Māori Cook Island individuals. We show novel, possibly population-specific configuration (AAAGG)10-25(AAGGG)exp, which...
To develop, test, and iterate a comprehensive neuromuscular targeted gene panel in national referral center.
Predicting the impact of coding and noncoding variants on splicing is challenging, particularly in non-canonical splice sites, leading to missed diagnoses patients. Existing prediction tools are complementary but knowing which use for each context remains difficult. Here, we describe Introme, uses machine learning integrate predictions from several detection tools, additional rules, gene architecture features comprehensively evaluate likelihood a variant impacting splicing. Through extensive...
Genomes of organisms are constructed by assembling sequence reads from whole genome sequencing.It is useful to determine read-coverage assemblies, for instance identifying duplication or deletion events, related contigs binning metagenomes (Mallawaarachchi et al., 2021;Mallawaarachchi & Lin, 2022), analysing taxonomic compositions (Wu 2023).Although calculating readcoverage a routine task, it typically involves several complete read and write operations (I/O operations).This not problem...
Abstract Background Modern sequencing technologies offer extraordinary opportunities for virus discovery and virome analysis. Annotation of viral sequences from metagenomic data requires a complex series steps to ensure accurate annotation individual reads assembled contigs. In addition, varying study designs will require project-specific statistical analyses. Findings Here we introduce Hecatomb, bioinformatic platform coordinating commonly used tasks required Hecatomb means “a great...
This study shows a causal association between ALDH1A2 variants and novel, severe multiple congenital anomaly syndrome in humans that is neonatally lethal due to associated pulmonary hypoplasia respiratory failure. In two families, exome sequencing identified compound heterozygous missense ALDH1A2. involved the conversion of retinol (vitamin A) into retinoic acid (RA), which an essential regulator diaphragm cardiovascular formation during embryogenesis. Reduced RA causes cardiovascular,...
Abstract Background Analysis of viral diversity using modern sequencing technologies offers extraordinary opportunities for discovery. However, these analyses present a number bioinformatic challenges due to genetic and virome complexity. Due the lack conserved marker sequences, metagenomic detection sequences requires non-targeted, random (shotgun) approach. Annotation enumeration relies on rigorous quality control effective search strategies against appropriate reference databases. Virome...
ABSTRACT Individuals affected by inherited neuromuscular diseases often present with a specific pattern of muscle weakness, which can guide clinicians in genetic investigations and variant interpretation. Nonetheless, more than 50% cases do not receive diagnosis. Oculopharyngodistal myopathy (OPDM) is an manifesting particular combination ptosis, dysphagia distal weakness. Pathologically it characterised rimmed vacuoles intranuclear inclusions on biopsy. In recent years GCC • CCG repeat...
ABSTRACT Background Neurogenetic disorders caused by pathogenic variants in four genes encoding non-erythrocytic spectrins ( SPTAN1, SPTBN1, SPTBN2, SPTBN4) range from peripheral and central nervous system involvement to complex syndromic presentations. Heterozygous SPTAN1 are exemplary for this diversity with phenotypes spanning almost the entire spectrum. Methods Through international collaboration we identified 14 families genetically unsolved distal weakness unreported heterozygous...
Neurodevelopmental disorders (NDDs) have dramatically increased in prevalence to an alarming one six children, and yet both causes preventions remain elusive. Recent human epidemiology animal studies implicated developmental exposure pyrethroid pesticides, of the most common classes pesticides US, as environmental risk factor for autism neurodevelopmental disorders. Our previous research has shown that low-dose chronic (DPE) changes folate metabolites adult mouse brain. We hypothesize DPE...