The DNA sequence of human chromosome 21

TLDR

Chromosome 21, the smallest human autosome, is implicated in Down syndrome, contains loci for monogenic and complex disorders, and shows loss of heterozygosity in tumor-associated regions. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We sequenced 33.5 million bp of 21q with high accuracy, achieving a largest contig of 25.5 Mb and leaving only three clone gaps and seven sequencing gaps (~100 kb), and also sequenced 281 kb of 21p. The assembly covers 99.7% of 21q, identifies duplications and repeat structures, and catalogs 127 known genes, 98 predicted genes, and 59 pseudogenes.

Abstract

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.