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

Journal Article · Thu Aug 10 04:00:00 EDT 1995 · Genomics

DOI:https://doi.org/10.1006/geno.1995.1166· OSTI ID:390660

Lyle, R; Wright, T J; Clark, L N; Hewitt, J E ^[1]

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1. Univ. of Manchester (United Kingdom)

Facioscapulohumeral muscular dystrophy (FSHD) is in 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. 44 refs., 7 figs.

• OSTI ID: 390660
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 28; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ACROCENTRIC CHROMOSOMES
BIOLOGICAL MARKERS
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
ELECTROPHORESIS
FLUORESCENCE
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 14
HYBRIDIZATION
NERVOUS SYSTEM DISEASES
POLYMERASE CHAIN REACTION
SOMATIC CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS