, Volume 105, Issue 3, pp 180–189 | Cite as

Analysis of the organisation and localisation of the FSHD-associated tandem array in primates: Implications for the origin and evolution of the 3.3 kb repeat family

  • Lorraine N. Clark
  • Udo Koehler
  • David C. Ward
  • Johannes Wienberg
  • Jane E. Hewitt
Original Articles


The D4Z4 locus is a polymorphic tandem repeat sequence on human chromosome 4q35. This locus is implicated in the neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD). The majority of sporadic cases of FSHD are associated withde novo DNA deletions within D4Z4. However, it is still not known how this rearrangement causes FSHD. Although the repeat contains homeobox sequences, despite exhaustive searching, no transcript from this locus has been identified. Therefore, it has been proposed that the deletion may invoke a position effect on a nearby gene. In order to try to understand the role of the D4Z4 repeat in this disease, we decided to investigate its conservation in other species. In this study, the long-range organisation and localisation of loci homologous to D4Z4 were investigated in primates using Southern blot analysis, pulsed field gel electrophoresis and fluorescencein situ hybridisation. In humans, probes to D4Z4 identify, in addition to the 4q35 locus, a closely related tandem repeat at 10qter and many related repeat loci mapping to the acrocentric chromosomes; a similar pattern was seen in all the great apes. In Old World monkeys, however, only one locus was detected in addition to that on the homologue of human chromosome 4, suggesting that the D4Z4 locus may have originated directly from the progenitor locus. The finding that tandem arrays closely related to D4Z4 have been maintained at loci homologous to human chromosome 4q35-qter in apes and Old World monkeys suggests a functionally important role for these sequences.


World Monkey Acrocentric Chromosome Tandem Array Repeat Family Yeast Artificial Chromosome Clone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Lorraine N. Clark
    • 1
  • Udo Koehler
    • 2
  • David C. Ward
    • 3
  • Johannes Wienberg
    • 2
  • Jane E. Hewitt
    • 1
  1. 1.School of Biological Sciences, 3.239 Stopford BuildingThe University of ManchesterManchesterUK
  2. 2.Institute of Anthropology and Human GeneticsLudwig-Maximilian UniversityMunichGermany
  3. 3.Department of GeneticsYale University School of MedicineNew HavenUSA

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