A high-resolution physical map of human chromosome 21p using yeast artificial chromosomes

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 a crocentric chromosomes. Owing to its repetitive nature and the lack of chro mosome 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 centromer e of chromosome 21 were constructed, including four polymorphic simple tand em repeats (STRs) and two expressed sequence tags (ESTs). Thirty YACs were selected From the St. Louis YAC library, the chromosome 21-enriched ICRF YA C 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 21 p12. 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 enzy me fingerprinting and fluorescence in situ hybridization (FISH). One gap wi th an estimated size of 400 kb remained near the telomeric end of the conti g. This YAC contig map of the short arm of human chromosome 21 constitutes a basic framework for Further structural and functional studies of chromoso me 21p.