A High-Resolution Physical Map of Human Chromosome 21p Using Yeast Artificial Chromosomes

  1. Sheng-Yue Wang1,
  2. Marc Cruts1,
  3. Jurgen Del-Favero1,
  4. Yi Zhang1,
  5. Fadel Tissir1,
  6. Marie-Claude Potier2,
  7. David Patterson3,
  8. Dean Nizetic4,
  9. Assumpció Bosch5,
  10. Haiming Chen6,
  11. Lynda Bennett7,
  12. Xavier Estivill5,
  13. Anna Kessling7,
  14. Stylianos E. Antonarakis6, and
  15. Christine van Broeckhoven1,8
  1. 1Flanders Interuniversity Institute for Biotechnology (VIB), Born-Bunge Foundation (BBS), Department of Biochemistry, University of Antwerp (UIA), B-2610 Antwerpen, Belgium; 2Laboratory of Neurobiology, Centre National de la Recherche Scientifique Unité Mixte de Rechere (CNRS–URA), 2054 Paris, France; 3Eleanor Roosevelt Institute for Cancer Research, Denver, Colorado 80206 USA; 4Centre for Applied Molecular Biology, School of Pharmacy, University of London, XC1N 1AX London, UK; 5Medical and Molecular Genetics Center—Institut de Recerca Oncològica, Hospital Duran i Reynals, l'Hospitalet de Llobregat, Barcelona 08907 Catalonia, Spain; 6Division of Medical Genetics, University of Geneva Medical School and Cantonal Hospital of Geneva, 1211 Geneva, Switzerland; 7Academy Unit of Medical and Community Genetics, Imperial College, HA13UJ London, UK.

Abstract

The short arm of human chromosome 21 (21p) contains many different types of repetitive sequences and is highly homologous to the short arms of other acrocentric chromosomes. Owing to its repetitive nature and the lack of chromosome 21p-specific molecular markers, most physical maps of chromosome 21 exclude this region. We constructed a physical map of chromosome 21p using sequence tagged site (STS) content mapping of yeast artificial chromosomes (YACs). To this end, 39 STSs located on the short arm or near the centromere of chromosome 21 were constructed, including four polymorphic simple tandem repeats (STRs) and two expressed sequence tags (ESTs). Thirty YACs were selected from the St. Louis YAC library, the chromosome 21-enriched ICRF YAC library, and the CEPH YAC and megaYAC libraries. These were assembled in a YAC contig map ranging from the centromere to the rDNA gene cluster at 21p12. The total size of the region covered by YACs is estimated between 2.9 and 5 Mb. The integrity of the YAC contig was confirmed by restriction enzyme fingerprinting and fluorescence in situ hybridization (FISH). One gap with an estimated size of 400 kb remained near the telomeric end of the contig. This YAC contig map of the short arm of human chromosome 21 constitutes a basic framework for further structural and functional studies of chromosome 21p.

Footnotes

  • 8 Corresponding author

  • E-MAIL cvbroeck{at}uia.ua.ac.be; FAX 323 8202541.

    • Received December 14, 1998.
    • Accepted August 17, 1999.
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