Vol. 9, Issue 11, 1059-1073, November 1999

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

¹ Flanders Interuniversity Institute for Biotechnology (VIB), Born-Bunge Foundation (BBS), Department of Biochemistry, University of Antwerp (UIA), B-2610 Antwerpen, Belgium; ² Laboratory of Neurobiology, Centre National de la Recherche Scientifique Unité Mixte de Rechere (CNRS-URA), 2054 Paris, France; ³ Eleanor Roosevelt Institute for Cancer Research, Denver, Colorado 80206 USA; ⁴ Centre for Applied Molecular Biology, School of Pharmacy, University of London, XC1N 1AX London, UK; ⁵ Medical and Molecular Genetics CenterInstitut de Recerca Oncològica, Hospital Duran i Reynals, l'Hospitalet de Llobregat, Barcelona 08907 Catalonia, Spain; ⁶ Division of Medical Genetics, University of Geneva Medical School and Cantonal Hospital of Geneva, 1211 Geneva, Switzerland; ⁷ Academy Unit of Medical and Community Genetics, Imperial College, HA13UJ London, UK.

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.