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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

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Abstract

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.

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Author notes

  1. Lorraine N. Clark

    Present address: Department of Neurology, School of Medicine, San Francisco General Hospital, San Francisco, USA

  2. Johannes Wienberg

    Present address: Department of Pathology, Tennis Court Road, Cambridge, UK

Authors and Affiliations

  1. School of Biological Sciences, 3.239 Stopford Building, The University of Manchester, Oxford Road, M13 9PT, Manchester, UK

    Lorraine N. Clark & Jane E. Hewitt

  2. Institute of Anthropology and Human Genetics, Ludwig-Maximilian University, Munich, Germany

    Udo Koehler & Johannes Wienberg

  3. Department of Genetics, Yale University School of Medicine, 06510, New Haven, CT, USA

    David C. Ward

Authors
  1. Lorraine N. Clark
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  2. Udo Koehler
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  3. David C. Ward
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  4. Johannes Wienberg
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  5. Jane E. Hewitt
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Corresponding author

Correspondence to Jane E. Hewitt.

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Edited by: H.F. Willard

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Clark, L.N., Koehler, U., Ward, D.C. et al. 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. Chromosoma 105, 180–189 (1996). https://doi.org/10.1007/BF02509499

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  • DOI: https://doi.org/10.1007/BF02509499

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