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Neurogenetics

, Volume 2, Issue 1, pp 18–23 | Cite as

Fine localization of the CMT4A locus using a PAC contig and haplotype analysis

  • Kamel Ben Othmane
  • Julie M. Rochelle
  • Mongi Ben Hamida
  • Brandon Slotterbeck
  • Nagesh Rao
  • Faycal Hentati
  • Margaret A. Pericak-Vance
  • J. M. Vance
Original article

ABSTRACT

Charcot-Marie-Tooth disease type 4A (CMT4A) is a severe, autosomal recessive peripheral neuropathy linked to chromosome 8q13-q21. We have previously constructed a YAC contig across the CMT4A region and narrowed the disease-flanking interval to approximately three megabases. Subsequently, we constructed a PAC/BAC contig made of 44 clones and mapped 44 new and 30 previous STSs, ESTs, and polymorphic makers to the region. Using 13 polymorphic markers, we have now identified an ancestral haplotype segregating in three families, indicating a common founder mutation. Two ancestral recombination events in this haplotype significantly reduce the minimal candidate region to a minimal trailing path of five PAC/BAC clones, which will now allow direct investigation of candidate genes for CMT4A.

Key words Charcot-Marie-Tooth CMT4A Haplotype analysis PAC contigs 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Kamel Ben Othmane
    • 1
  • Julie M. Rochelle
    • 1
  • Mongi Ben Hamida
    • 2
  • Brandon Slotterbeck
    • 1
  • Nagesh Rao
    • 3
  • Faycal Hentati
    • 2
  • Margaret A. Pericak-Vance
    • 1
  • J. M. Vance
    • 1
  1. 1.Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, NC 27710-2903, USAUS
  2. 2.Institut National de Neurologie, La Rabta, Tunis, Tunisia
  3. 3.Department of Pathology and Laboratory Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California, USAUS

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