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.

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      Interestingly, at 4q35 the deletion of an integral number of D4Z4 units was associated with sporadic and familial cases of the facioscapulohumeral muscular dystrophy (FSHD) syndrome (van Deutekom et al., 1993; Wijmenga et al., 1992). In the attempt to identify the gene responsible of the FSHD, 160 kb of the 4q subtelomeric region have been sequenced (van Geel et al., 1999). This region contains FRG1 and TUB4q genes, potential coding regions, pseudogenes, high density of interspersed repeats, a polymorphic array of D4Z4 repeats and a beta satellite block.

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    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].

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