A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus

David Pellerin; Giulia F. Del Gobbo; Madeline Couse; Egor Dolzhenko; Sathiji K. Nageshwaran; Warren A. Cheung; Isaac R. L. Xu; Marie-Josee Dicaire; Guinevere Spurdens; Gabriel Matos-Rodrigues; Igor Stevanovski; Carolin K. Scriba; Adriana Rebelo; Virginie Roth; Marion Wandzel; Celine Bonnet; Catherine Ashton; Aman Agarwal; Cyril Peter; Dan Hasson; Nadejda M. Tsankova; Ken Dewar; Phillipa J. Lamont; Nigel G. Laing; Mathilde Renaud; Henry Houlden; Matthis Synofzik; Karen Usdin; Andre Nussenzweig; Marek Napierala; Zhao Chen; Hong Jiang; Ira W. Deveson; Gianina Ravenscroft; Schahram Akbarian; Michael A. Eberle; Kym M. Boycott; Tomi Pastinen; Bernard Brais; Stephan Zuchner; Matt C. Danzi; All Us Res Program Long Read

doi:10.1038/s41588-024-01808-5

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A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus

Journal article

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A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus

David Pellerin, Giulia F. Del Gobbo, Madeline Couse, Egor Dolzhenko, Sathiji K. Nageshwaran, Warren A. Cheung, Isaac R. L. Xu, Marie-Josee Dicaire, Guinevere Spurdens, Gabriel Matos-Rodrigues, …

Nature genetics, Vol.56(7), pp.1366-1370

2024-07-01

DOI: https://doi.org/10.1038/s41588-024-01808-5

PMID: 38937606

Appears in Miller School of Medicine - Latest Publications

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

The factors driving or preventing pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 (GAA)<middle dot>(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a common 5 '-flanking variant in 70.34% of alleles analyzed (3,463/4,923) that represents the phylogenetically ancestral allele and is present on all major haplotypes. This common sequence variation is present nearly exclusively on nonpathogenic alleles with fewer than 30 GAA-pure triplets and is associated with enhanced stability of the repeat locus upon intergenerational transmission and increased Fiber-seq chromatin accessibility.

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Title: A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus
Creators: David Pellerin - McGill University
Giulia F. Del Gobbo - University of Ottawa
Madeline Couse - Hospital for Sick Children
Egor Dolzhenko - Pacific Biosciences
Sathiji K. Nageshwaran - Allen Institute for Brain Science
Warren A. Cheung - Children's Mercy Hospital
Isaac R. L. Xu - Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33136 USA
Marie-Josee Dicaire - McGill University
Guinevere Spurdens - Dr. John T. Macdonald Foundation
Gabriel Matos-Rodrigues - National Human Genome Research Institute
Igor Stevanovski - Garvan Institute of Medical Research
Carolin K. Scriba - Harry Perkins Institute of Medical Research
Adriana Rebelo - Dr. John T. Macdonald Foundation
Virginie Roth - CHRU Nancy, Lab Genet, Nancy, France
Marion Wandzel - CHRU Nancy, Lab Genet, Nancy, France
Celine Bonnet - CHRU Nancy, Lab Genet, Nancy, France
Catherine Ashton - Montreal Neurological Institute and Hospital
Aman Agarwal - Icahn School of Medicine at Mount Sinai
Cyril Peter - Allen Institute for Brain Science
Dan Hasson - Icahn School of Medicine at Mount Sinai
Nadejda M. Tsankova - Icahn School of Medicine at Mount Sinai
Ken Dewar - McGill University
Phillipa J. Lamont - Royal Perth Hospital
Nigel G. Laing - Harry Perkins Institute of Medical Research
Mathilde Renaud - CHRU Nancy, Lab Genet, Nancy, France
Henry Houlden - National Hospital for Neurology and Neurosurgery
Matthis Synofzik - Hertie Institute for Clinical Brain Research
Karen Usdin - National Institute of Diabetes and Digestive and Kidney Diseases
Andre Nussenzweig - National Cancer Institute
Marek Napierala - College Station Medical Center
Zhao Chen - Central South University
Hong Jiang - Central South University
Ira W. Deveson - Garvan Institute of Medical Research
Gianina Ravenscroft - Harry Perkins Institute of Medical Research
Schahram Akbarian - Icahn School of Medicine at Mount Sinai
Michael A. Eberle - Pacific Biosciences
Kym M. Boycott - Children's Hospital of Eastern Ontario
Tomi Pastinen - University of Missouri–Kansas City
Bernard Brais - McGill University
Stephan Zuchner
Matt C. Danzi - Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33136 USA
All Us Res Program Long Read
Publication Details: Nature genetics, Vol.56(7), pp.1366-1370
Publisher: NATURE PORTFOLIO
Number of pages: 18
Grant note: 189963 / Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) 2007681; 2023126 / Australian Medical Research Future Fund Genomics Health Futures Mission Grants Wellcome Trust Ontario Research Fund, Genome Quebec UCLH/UCL Biomedical Research Centre APP2007769 / Australian National Health and Medical Research Council (NHMRC); National Health & Medical Research Council (NHMRC) of Australia RF1DA048810; DP1DA056018 / National Institute on Drug Abuse; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) Genome Canada R01NS106229 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 2021YFA0805200 / National Key R&D Program of China
Academic Unit: Leadership Department; Miller School of Medicine; John P. Hussman Institute for Human Genomics
Language: English
Resource Type: Journal article
PMID: 38937606
Record Identifier: 991032860893102976