During the first 10 years of Genomics (1987-1997), the molecular structure of human chromosome 21 (HC21) has been intensively investigated. Due to its small size and involvement in Down syndrome, it continues to serve as a model in the development of "genomics technologies." Increasingly more detailed genetic, radiation hybrid, physical, and transcription maps, in addition to NotI restriction and chromosomal breakpoint maps, of HC21 have been developed, and approximately 10% of its genes have been cloned. These maps have been vital in the localization of loci for 15 monogenic disorders to HC21, and 10 of these genes have been identified and characterized. The genetic maps have aided in the detailed elucidation of the origin of the supernumerary HC21 in trisomy 21 from investigations of recombination and nondisjunction events. Mouse models of Down syndrome, with partial trisomy 16, the mouse chromosome principally syntenic to HC21, have been created and initially characterized. A substantial number of the above studies related to the molecular mapping, gene cloning, and infrastructure of HC21 were published in Genomics (e.g., approximately 30% of papers describing HC21 maps were published here). The future goals of genomic analysis of HC21 will be the determination of its complete nucleotide sequence and the identification and functional analysis of all of its genes. These advances will help to provide a molecular explanation of the pathophysiology of Down syndrome and aid in the identification of genes for monogenic and polygenic disorders that map on this chromosome. Novel therapeutic interventions for Down syndrome and the monogenic and polygenic disorders that map to HC21 will be designed and tried based on the knowledge of the disease pathogenesis resulting from the genomic analysis.
Copyright 1998 Academic Press.