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

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.

Islands of euchromatin-like sequence and expressed polymorphic sequences within the short arm of human chromosome 21

“…The nonredundant positive clones (3208) were re-arrayed into 384-well plates and gridded on nylon membrane for screening with 21p-specific probes. To identify specific 21p BACs, overgo probes were designed to STSs corresponding to the YAC ends 2E4R, 2E4L, 4E9L, 4E9R, 1B8L, 2C2R, 2C9R from Wang et al (1999). The library clone size distribution is given in Supplemental Figure 2, and a summary of the library screens is given in Supplemental Tables 1, 2.…”

“…Wang et al (1999) constructed a YAC contig of the proximal part of HSA21p, between the RNR gene cluster and the centromere. This map provides the best physical map of an acrocentric short arm to date and provides a framework for further studies of 21p since it provides locations for STS markers.…”

De novoSCN1Amutations are a major cause of severe myoclonic epilepsy of infancy

“…To test paternity, we genotyped the multiallelic microsatellite marker D21S188 [Wang et al, 1999] by PCR amplification of genomic DNA and analyzed the alleles on the ABI 3700 sequencer using Genotyper s 3.6 (Applied Biosystems). This chromosome 21p (CA) n dinucleotide repeat marker shows, on average, 16 different alleles derived from eight different chromosomes.…”

Genomic structure of a copy of the human TPTE gene which encompasses 87 kb on the short arm of chromosome 21

“…We have recently identified a cDNA, named TPTE (Transmembrane Phosphatase with Tensin homology), encoding a predicted protein of 551 amino acids with potential transmembrane domains, a tyrosine phosphatase motif and sequence homology to several phosphatases including the tumor suppresser PTEN (Chen et al 1999). The gene is strongly expressed exclusively in testis.…”