Chromosoma

, 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

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.

Keywords

World Monkey Acrocentric Chromosome Tandem Array Repeat Family Yeast Artificial Chromosome Clone 

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References

  1. Agresti A, Meneveri R, Siccardi A, Marozzi A, Corneo G, Gaudi S, Ginelli E (1989) Linkage in human heterochromatin between highly divergentSau3A repeats and a new family of repeated DNA sequences (HaeIII family). J. Mol Biol 205: 625–631PubMedCrossRefGoogle Scholar
  2. Altherr MR, Bengtsson U, Markovich RP, Winokur ST (1995) Efforts toward understanding the molecular basis of facioscapulohumeral dystrophy. Muscle Nerve Suppl 2:S32-S38CrossRefGoogle Scholar
  3. Assum G, Fink T, Steinbeißer T, Fisel K (1993) Analysis of human extrachromosomal DNA elements originating from different β-satellite subfamilies. Hum Genet 91:489–495PubMedCrossRefGoogle Scholar
  4. Assum G, Gartmann C, Schempp W, Wohr G (1994) Evolution of the chAB4 multisequence family in primates. Genomics 21:34–41PubMedCrossRefGoogle Scholar
  5. Bakker E, Wijmenga C, Vossen R, Padberg GW, Hewitt JE, Vanderwielen M, Rasmussen K, Frants RR (1995) The FSHD-linked locus D4F104S1 (p13E-11) on 4q35 has a homologue on 10qter. Muscle Nerve Suppl 2:S39-S44CrossRefGoogle Scholar
  6. Bengtsson U, Altherr MR, Wasmuth JJ, Winokur ST (1994) High resolution fluorescencein situ hybridisation to linearly extended DNA visually maps a tandem repeat associated with facioscapulohumeral muscular dystrophy immediately adjacent to the telomere of 4q. Hum Mol Genet 3:1801–1805PubMedGoogle Scholar
  7. Caccone A, Powell JR (1989) DNA divergence among hominoids. Evolution 43:925–942CrossRefGoogle Scholar
  8. Choo KH, Vissel B, Brown R, Filby RG, Earle E (1988) Homologous alpha satellite sequences on human acrocentric chromo-somes with selectivity for chromosomes 13, 14 and 21: implications for recombination between nonhomologous and Robertsonian translocations. Nucleic Acids Res 16:1273–1284PubMedGoogle Scholar
  9. Church GM, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci USA 81:1991–1995PubMedCrossRefGoogle Scholar
  10. Deidda G, Cacurri S, Grisanti P, Vigneti E, Piazzo N, Felicetti L (1995) Physical mapping evidence for a duplicated region on chromosome 10qter showing high homology with the FSHD locus on chromosome 4qter. Eur J Hum Genet 3:155–167PubMedGoogle Scholar
  11. Hewitt JE, Lyle R, Clark LN, Valleley EM, Wright TJ, Wijmenga C, van Deutekom JCT, Francis F, Sharpe PT, Hofker M, Frants RR, Williamson R (1994) Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Hum Mol Genet 3:1287–1295PubMedGoogle Scholar
  12. Jauch A, Wienberg J, Stanyon R, Arnold N, Tofanelli S, Ishida T, Cremer T (1992) Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting. Proc Natl Acad Sci USA 89:8611–8615PubMedCrossRefGoogle Scholar
  13. Kurnit DM, Roy S, Stewart GD, Schwedock J, Neve RL, Bruns GAP, Van Keuren MI, Patterson D (1986) The 724 family of DNA sequences is interspersed about the pericentromeric regions of human acrocentric chromosomes. Cytogenet Cell Genet 43:109–116PubMedCrossRefGoogle Scholar
  14. Lunt PW, Harper PS (1991) Genetic counselling in facioscapulohumeral muscular dystrophy. J Med Genet 28:665–664PubMedCrossRefGoogle Scholar
  15. Lyle R, Wright TJ, Clark LN, Hewitt JE (1995) The FSHD-associated repeat, D4Z4, is a member of a dispersed family of homeobox-containing repeats, subsets of which are clustered on the short arms of the acrocentric chromosomes. Genomics 28:389–397PubMedCrossRefGoogle Scholar
  16. Meneveri R, Agresti A, Marozzi A, Saccone S, Rocchi M, Archidiacono N, Corneo G, Valle GD, Ginelli E (1993) Molecular organisation and chromosomal location of human GC-rich heterochromatic blocks. Gene 123:227–234PubMedCrossRefGoogle Scholar
  17. Meneveri R, Agresti A, Marozzi A, Ginelli E (1995) Analysis of GC-rich repetitive nucleotide sequences in great apes. J Mol Evol 40:405–412PubMedCrossRefGoogle Scholar
  18. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedGoogle Scholar
  19. Passos-Bueno MR, Wijmenga C, Takata RE, Marie SKN, Vainzof M, Pavanello RC, Hewitt JE, Bakker E, Carvalho A, Akiyama J, Frants RR, Zatz M (1993) No evidence of genetic heterogeneity in Brazilian facioscapulohumeral muscular dystrophy families (FSHD) with 4q markers. Hum Mol Genet 2:557–562PubMedGoogle Scholar
  20. Pavelitz T, Rusché L, Matera AG, Scharf JM, Weiner AM (1995) Concerted evolution of the tandem array encoding primate U2 snRNA occursin situ, without changing the cytological context of theRNU2 locus. EMBO J 14:169–177PubMedGoogle Scholar
  21. Ried T, Arnold N, Ward DC Wienberg J (1993) Comparative high-resolution mapping of human and primate chromosomes by fluorescencein situ hybridization. Genomics 18:381–386PubMedCrossRefGoogle Scholar
  22. Sibley C, Comstock J, Ahlquist J (1990) DNA hybridisation evidence of hominoid phylogeny: a reanalysis of the data. J Mol Evol 30:202–236PubMedCrossRefGoogle Scholar
  23. Tyler-Smith C, Willard HF (1993) Mammalian chromosome structure. Curr Opin Genet Dev 3:390–397PubMedCrossRefGoogle Scholar
  24. Upadhyaya M, Jardine P, Maynard J, Farnham J Sarfarazi M, Wijmenga C, Hewitt JE, Frants R, Harper PS, Lunt PW (1993) Molecular analysis of British facioscapulohumeral dystrophy families of 4q DNA rearrangements. Hum Mol Genet 2:981–987PubMedGoogle Scholar
  25. van Deutekom JCT, Wijmenga C, van Tienhoven EAE, Gruter AM, Hewitt JE, Padberg GW, van Ommen G-JB, Hofker MH, Frants RR (1993) FSHD associated rearrangements are due to deletion of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet 2:2037–2042PubMedGoogle Scholar
  26. van Deutekom JCY, Hofker MH, Romberg S, van Geel M, Rommens J, Wright TJ, Hewitt JE, Padberg GW, Wijmenga C, Frants RR (1995) Search for the FSHD gene using cDNA selection in a region spanning 100 kb on chromosome 4q35. Muscle Nerve Suppl 2:S19-S26CrossRefGoogle Scholar
  27. van Deutekom J, Lemmers R, Grewal P, van Geel M, Romberg S, Dauwerse H, Wright T, Padberg G, Hofker M, Hewitt J, Frants R (1996) Identification of the first gene (FRG1) from the FSHD region on human chromosome 4q35. Hum Mol Genet 5:581–589PubMedCrossRefGoogle Scholar
  28. Weiffenbach B, Dubois J, Storvick D, Tawil R, Jacobsen SJ Gilbert J, Wijmenga C, Mendell JR, Winokur S, Altherr MR, Schultz P, Olandt S, Frants RR, Pericak-Vance M, Griggs RC (1993) Mapping the facioscapulohumeral muscular dystrophy gene is complicated by chromosome 4q35 recombination events. Nat Genet 4:165–169PubMedCrossRefGoogle Scholar
  29. Wijmenga C, Hewitt JE, Sandkuijl LA, Clark LN, Wright TJ, Dauwerse HG, Gruter A-M, Hofker MH, Moerer P, Williamson R, van Ommen G-JB, Padberg GW, Frants RR (1992) Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy. Nat Genet 2:26–30PubMedCrossRefGoogle Scholar
  30. Wijmenga C, van Deutekom JCT, Hewitt JE, Padberg GW, van Ommen G-JB, Hofker MH, Frants RR (1994) Pulsed-field gel electrophoresis of the D4F104S1 locus reveals the size and parental origin of the facioscapulohumeral muscular dystrophy (FSHD)-associated deletions. Genomics 19:21–26PubMedCrossRefGoogle Scholar
  31. Winokur ST, Bengtsson U, Feddersen J, Mathews KD, Weiffenbach B, Bailey H, Markovich RP, Murray JC, Wasmuth JJ, Altherr MR, Schutte BC (1994) The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin-associated repetitive element: implications for a role of chromatin structure in the pathogenesis of the disease. Chromosome Res 2:225–234PubMedCrossRefGoogle Scholar
  32. Wright TJ, Wijmenga C, Clark LC, Frants RR, Williamson R, Hewitt JE (1993) Fine mapping of the FSHD gene region orientates the rearranged fragment detected by the probe p13E-11. Hum Mol Genet 2:1673–1678PubMedGoogle Scholar
  33. Zhang X-Y, Loflin PT, Gehrke CW, Andrews PA, Ehrlich M (1987) Hypermethylation of human DNA sequences in embryonic carcinoma cells and somatic tissues but not in sperm. Nucleic Acids Res 15:9429–9449PubMedGoogle Scholar

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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