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.