The DNA sequence of human chromosome 21 was sequenced by an international consortium, revealing 33.5 million base pairs (bp) of the long arm (21q) with 99.7% coverage, and 281,116 bp from the short arm (p). The sequence includes 127 known genes, 98 predicted genes, and 59 pseudogenes. Chromosome 21 is the smallest human autosome and is associated with Down syndrome, caused by trisomy 21. The sequence analysis identified duplications, repeat structures, and structural features, including a 7-Mb region with only one gene. The gene catalog includes 225 genes and 59 pseudogenes, with 127 known genes and 98 predicted genes. The sequence also revealed structural features such as duplications, breakpoints, and syntenic regions with other chromosomes. The study highlights the importance of chromosome 21 in genetic disorders, including Down syndrome, monogenic disorders, and complex diseases. The sequence provides a foundation for understanding the molecular mechanisms of these conditions and for developing diagnostic and therapeutic approaches. The data also support the conclusion that chromosome 21 is gene-poor compared to chromosome 22, which is gene-rich. The study has significant implications for understanding the pathogenesis of diseases and the development of new therapeutic strategies. The sequence data and gene catalog are valuable resources for further research into the genetic basis of various conditions.The DNA sequence of human chromosome 21 was sequenced by an international consortium, revealing 33.5 million base pairs (bp) of the long arm (21q) with 99.7% coverage, and 281,116 bp from the short arm (p). The sequence includes 127 known genes, 98 predicted genes, and 59 pseudogenes. Chromosome 21 is the smallest human autosome and is associated with Down syndrome, caused by trisomy 21. The sequence analysis identified duplications, repeat structures, and structural features, including a 7-Mb region with only one gene. The gene catalog includes 225 genes and 59 pseudogenes, with 127 known genes and 98 predicted genes. The sequence also revealed structural features such as duplications, breakpoints, and syntenic regions with other chromosomes. The study highlights the importance of chromosome 21 in genetic disorders, including Down syndrome, monogenic disorders, and complex diseases. The sequence provides a foundation for understanding the molecular mechanisms of these conditions and for developing diagnostic and therapeutic approaches. The data also support the conclusion that chromosome 21 is gene-poor compared to chromosome 22, which is gene-rich. The study has significant implications for understanding the pathogenesis of diseases and the development of new therapeutic strategies. The sequence data and gene catalog are valuable resources for further research into the genetic basis of various conditions.