The FSHD region on human chromosome 4q35 contains potential coding regionsamong pseudogenes and a high density of repeat elements

The distal end of chromosome 4q contains the locus involved in facioscapulo humeral muscular dystrophy (FSHD1). Specific genomic deletions within a tan dem 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 homolo gies, 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 se quences, several additional potential coding regions were identified by ana lyzing the sequence with exon prediction programs. So far, we have been una ble to demonstrate transcripts by RT-PCR or cDNA library hybridization, How ever, several retrotransposed pseudogenes were identified. The high density of pseudogenes and repeat elements is consistent with the subtelomeric loc ation of this region and explains why previous transcript identification st udies have been problematic. (C) 1999 Academic Press.