Elsevier

Genomics

Volume 61, Issue 1, 1 October 1999, Pages 55-65
Genomics

Regular Article
The FSHD Region on Human Chromosome 4q35 Contains Potential Coding Regions among Pseudogenes and a High Density of Repeat Elements

https://doi.org/10.1006/geno.1999.5942Get rights and content

Abstract

The distal end of chromosome 4q contains the locus involved in facioscapulohumeral muscular dystrophy (FSHD1). Specific genomic deletions within a tandem DNA repeat (D4Z4) are associated with the disease status, but no causal genes have yet been discovered. In a systematic search for genes, a 161-kb stretch of genomic DNA proximal to D4Z4 was sequenced, analyzed for homologies, and subjected to gene prediction programs. A major fraction (45%) of the subtelomeric region is composed of repeat sequences attributable mainly to LINE-1 elements. Apart from the previously identified FRG1 and TUB4q sequences, several additional potential coding regions were identified by analyzing the sequence with exon prediction programs. So far, we have been unable to demonstrate transcripts by RT-PCR or cDNA library hybridization. However, several retrotransposed pseudogenes were identified. The high density of pseudogenes and repeat elements is consistent with the subtelomeric location of this region and explains why previous transcript identification studies have been problematic.

References (43)

  • A.F. Smit et al.

    Ancestral, mammalian-wide subfamilies of LINE-1 repetitive sequences

    J. Mol. Biol.

    (1995)
  • C. Wijmenga et al.

    Location of facioscapulohumeral muscular dystrophy gene on chromosome 4

    Lancet

    (1990)
  • M.R. Altherr et al.

    Efforts toward understanding the molecular basis of facioscapulohumeral muscular dystrophy

    Muscle Nerve

    (1995)
  • M.A. Ansari-Lari et al.

    Large-scale sequencing in human chromosome 12p13: Experimental and computational gene structure determination

    Genome Res.

    (1997)
  • D. Benson et al.

    GenBank

    Nucleic Acids Res.

    (1993)
  • E.H. Blackburn

    Structure and function of telomeres

    Nature

    (1991)
  • J.M. Claverie

    Computational methods for the identification of genes in vertebrate genomic sequences

    Hum. Mol. Genet.

    (1997)
  • B. Ewing et al.

    Base-calling of automated sequencer traces using phred. II. Error probabilities

    Genome Res.

    (1998)
  • B. Ewing et al.

    Base-calling of automated sequencer traces using phred. I. Accuracy assessment

    Genome Res.

    (1998)
  • J. Flint et al.

    Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

    Hum. Mol. Genet.

    (1997)
  • D. Garrick et al.

    Repeat-induced gene silencing in mammals

    Nat. Genet.

    (1998)
  • Cited by (0)

    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. U85056, U89471, and AF146191.

    1

    Present address: Division of Genetics, Queen's Medical Centre, Nottingham University, Nottingham, UK.

    2

    To whom correspondence should be addressed at Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Telephone: (716) 845-3168. Fax: (716) 845-1698. E-mail: [email protected].

    View full text