Elsevier

Genomics

Volume 28, Issue 3, 10 August 1995, Pages 389-397
Genomics

Regular Article
The FSHD-Associated Repeat, D4Z4, Is a Member of a Dispersed Family of Homeobox-Containing Repeats, Subsets of Which Are Clustered on the Short Arms of the Acrocentric Chromosomes

https://doi.org/10.1006/geno.1995.1166Get rights and content

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that maps to human chromosome 4q35. FSHD is tightly linked to a polymorphic 3.3-kb tandem repeat locus, D4Z4. D4Z4 is a complex repeat: it contains a novel homeobox sequence and two other repetitive sequence motifs. In most sporadic FSHD cases, a specific DNA rearrangement, deletion of copies of the repeat at D4Z4, is associated with development of the disease. However, no expressed sequences from D4Z4 have been identified. We have previously shown that there are other loci similar to D4Z4 within the genome. In this paper we describe the isolation of two YAC clones that map to chromosome 14 and that contain multiple copies of a D4Z4-like repeat. Isolation of cDNA clones that map to the acrocentric chromosomes and Southern blot analysis of somatic cell hybrids show that there are similar loci on all of the acrocentric chromosomes. D4Z4 is a member of a complex repeat family, and PCR analysis of somatic cell hybrids shows an organization into distinct subfamilies. The implications of this work in relation to the molecular mechanism of FSHD pathogenesis is discussed. We propose the name 3.3-kb repeat for this family of repetitive sequence elements.

References (0)

Cited by (135)

  • Designed U7 snRNAs inhibit DUX4 expression and improve FSHD-associated outcomes in DUX4 overexpressing cells and FSHD patient myotubes

    2021, Molecular Therapy Nucleic Acids
    Citation Excerpt :

    When expressed in muscles, the DUX4 protein is toxic and activates genes associated with cell death, oxidative stress, impaired muscle differentiation, double-stranded RNA activation, immune responses, and atrophy.7–20 Potentially hundreds of DUX4 copies exist in the human genome, embedded within tandemly arrayed repetitive elements called D4Z4 repeats.21,22 Although each DUX4 copy could be transcribed, only one—located within the terminal D4Z4 repeat on the chromosome 4q35 subtelomere—is translated into toxic DUX4 protein in FSHD muscle.5

View all citing articles on Scopus
View full text