Interchromosomal repeat array interactions between chromosomes 4 and 10: amodel for subtelomeric plasticity

Chromosomal rearrangements occur more frequently in subtelomeric domains th an in other regions of the genome and are often associated with human patho logy. To further elucidate the plasticity of subtelomeric domains, we exami ned the 3.3 kb D4Z4 repeal array on chromosome 4 and its homologue on chrom osome 10 in 208 Dutch blood donors by pulsed field gel electrophoresis, The se subtelomeric repeats are known to rearrange and partial deletions of thi s polymorphic array on chromosome 4 are associated with facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant myopathy, Our results sho w that mitotic rearrangements occur frequently as 3% of individuals display somatic mosaicism for a repeat expansion or contraction explaining the hig h variability of subtelomeric repeat array sizes,, Translocated 4-type repe at arrays on chromosome 10 and the reverse configuration of 10-type repeat arrays on chromosome 4 are observed in 21% of individuals. The translocated repeat arrays on chromosome 4 tend to be more heterogeneous than 4-type re peats on chromosome 10, The repeat length on chromosome 4 is on average lar ger than on chromosome 10, But on both chromosomes we observe a multi-modal repeat length distribution with equidistant peaks at intervals of 65 kb, p ossibly reflecting a higher-order chromatin structure. Interestingly, in as many as six random blood donors (3%) we identified FSHD-sized 4-type repea t arrays. Assuming that these individuals are clinically unaffected, these results imply an incomplete penetrance In the upper range of FSHD alleles, Overall, the observed dynamic characteristics of these homologous domains m ay serve as a model for subtelomeric plasticity.