Poster Presentation 44th Lorne Genome Conference 2023

Ultra-long and targeted nanopore sequencing to resolve human macrosatellite epigenetics in health and disease (#228)

Lucinda Xiao 1 , Kathleen Zeglinski 1 , Ayush Semwal 1 , Frédérique Magdinier 2 , Matthew E Ritchie 1 , Marnie E Blewitt 1 , Quentin Gouil 1
  1. Walter and Eliza Hall Institute, Parkville, VIC, Australia
  2. Aix-Marseille University, Marseille, France

Epigenetic dysregulation of the D4Z4 locus in humans causes a muscular dystrophy called FSHD (FacioScapuloHumeral muscular Dystrophy). D4Z4 is one of the most challenging genomic regions to study, as a tandem array of large (3-kb) repeats. To resolve allele-specific genetic structure and DNA methylation, we use long-read nanopore sequencing. Combining whole-genome ultra-long sequencing with targeted (Cas9-mediated) sequencing of D4Z4 improves diagnosis of FSHD and sheds light on the role of epigenetic regulator SMCHD1 at this locus.