Polymorphism in satellite DNA has been associated with disease, a notable example being facioscapulohumeral muscular dystrophy (Box 7.2), which in almost all cases is associated with a reduced number of copies of a satellite repeat, dubbed D4Z4, at 4q35. Linkage studies had implicated the distal end of chromosome 4 in disease susceptibility and this was fine mapped to a subtelomeric region and specifically a region comprised of 3.3 kb repeats (Wijmenga et al. 1992). In unaffected individuals, between 11 and 100 copies of the repeat are found, while in patients between one and ten copies are observed on one of the two alleles. The phenotype is highly variable but, in general, having a lower number of repeat copies (between one and three) is associated with more severe disease occurring sporadically, while in familial cases four to ten copies are typically seen (Tawil and Van Der Maarel 2006). The molecular basis of the association remains unclear but is thought to involve epigenetic mechanisms (van Overveld et al. 2005) and a positional effect of the deletion modulating transcription of neighbouring genes (van Deutekom et al. 1996). Haplotypic analysis also suggests specific sequence differences may be important (Lemmers et al. 2007).
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