Interchromosomal repeat array interactions between chromosomes 4 and 10: a model for subtelomeric plasticity
| Autor: | George W. Padberg, Lodewijk A. Sandkuijl, Silvère M. van der Maarel, Richard J F L Lemmers, Rune R. Frants, Petra G.M. van Overveld, Giancarlo Deidda |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Mitosis Biology Translocation Genetic Chromosome regions Genetics medicine Humans Facioscapulohumeral muscular dystrophy Molecular Biology Genetics (clinical) Netherlands Repetitive Sequences Nucleic Acid Chromosomes Human Pair 10 Mosaicism Nucleic Acid Hybridization Chromosome General Medicine Telomere medicine.disease Muscular Dystrophy Facioscapulohumeral Electrophoresis Gel Pulsed-Field Chromosome 17 (human) Chromosome 4 Female Chromosomes Human Pair 4 Trinucleotide repeat expansion Chromosome 21 Chromosome 22 |
| Zdroj: | Human Molecular Genetics. 9:2879-2884 |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/9.19.2879 |
| Popis: | Chromosomal rearrangements occur more frequently in subtelomeric domains than in other regions of the genome and are often associated with human pathology. To further elucidate the plasticity of subtelomeric domains, we examined the 3.3 kb D4Z4 repeat array on chromosome 4 and its homologue on chromosome 10 in 208 Dutch blood donors by pulsed field gel electrophoresis. These subtelomeric repeats are known to rearrange and partial deletions of this polymorphic array on chromosome 4 are associated with facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant myopathy. Our results show that mitotic rearrangements occur frequently as 3% of individuals display somatic mosaicism for a repeat expansion or contraction explaining the high variability of subtelomeric repeat array sizes. Translocated 4-type repeat 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 repeats on chromosome 10. The repeat length on chromosome 4 is on average larger than on chromosome 10. But on both chromosomes we observe a multi-modal repeat length distribution with equidistant peaks at intervals of 65 kb, possibly reflecting a higher-order chromatin structure. Interestingly, in as many as six random blood donors (3%) we identified FSHD-sized 4-type repeat 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 may serve as a model for subtelomeric plasticity. |
| Databáze: | OpenAIRE |
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