The article reports the sequencing and gene catalog of the long arm of human chromosome 21, which is the smallest human autosome. The chromosome 21 mapping and sequencing consortium, involving multiple institutions, sequenced 33,546,361 base pairs (bp) of DNA with high accuracy, achieving 99.7% coverage of the chromosome. The sequence revealed 127 known genes, 98 predicted genes, and 59 pseudogenes. The study also identified structural features such as duplications and repeat structures, which may be involved in chromosomal abnormalities and genetic diseases. The gene catalog provides a foundation for understanding the molecular basis of Down syndrome and other genetic disorders, and will aid in the development of diagnostic tests and therapeutic approaches. The low gene density on chromosome 21 suggests that trisomy 21 is one of the few viable human autosomal trisomies. The complete sequence analysis will have significant implications for medical research and disease treatment.The article reports the sequencing and gene catalog of the long arm of human chromosome 21, which is the smallest human autosome. The chromosome 21 mapping and sequencing consortium, involving multiple institutions, sequenced 33,546,361 base pairs (bp) of DNA with high accuracy, achieving 99.7% coverage of the chromosome. The sequence revealed 127 known genes, 98 predicted genes, and 59 pseudogenes. The study also identified structural features such as duplications and repeat structures, which may be involved in chromosomal abnormalities and genetic diseases. The gene catalog provides a foundation for understanding the molecular basis of Down syndrome and other genetic disorders, and will aid in the development of diagnostic tests and therapeutic approaches. The low gene density on chromosome 21 suggests that trisomy 21 is one of the few viable human autosomal trisomies. The complete sequence analysis will have significant implications for medical research and disease treatment.