Journal article
Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS
H Rafehi, DJ Szmulewicz, MF Bennett, NLM Sobreira, K Pope, KR Smith, G Gillies, P Diakumis, E Dolzhenko, MA Eberle, MG Barcina, DP Breen, AM Chancellor, PD Cremer, MB Delatycki, BL Fogel, A Hackett, GM Halmagyi, S Kapetanovic, A Lang Show all
American Journal of Human Genetics | CELL PRESS | Published : 2019
Abstract
Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion ..
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Awarded by Murdoch Children's Research Institute
Funding Acknowledgements
We acknowledge access to the dataset EGA00001003562 from the European Genome-Phenome Archive. This work was supported by the Australian Government National Health and Medical Research Council (Program Grant 1054618 to M.B.), the NIH (NINDS grant R01NS082094 to B.L.F.), and the Murdoch Children's Research Institute. M.B. was supported by an NHMRC Senior Research Fellowship (1102971) and D.P.B. was supported by a Wellcome Clinical Research Career Development Fellowship. Additional funding was provided by the Independent Research Institute Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Program.