Criteria for gene identification and features of genome organization: analysis of 6.5 Mb of DNA sequence from human chromosome 21

Gene. 2000 Apr 18;247(1-2):215-32. doi: 10.1016/s0378-1119(00)00089-5.


To establish criteria for and the limitations of novel gene identification, to identify novel genes of potential relevance to Down Syndrome and to investigate features of genome organization, 6. 550kb. In total, 41 novel gene models were predicted, and for a subset of these, RT-PCR experiments helped to verify and refine the models, and were used to assess expression in early development and in adult brain regions of potential relevance to Down syndrome. Results suggest generally low and/or restricted patterns of expression, and also reveal examples of complex alternative processing, especially in brain, that may have important implications for regulation of protein function. Analysis of complete gene structures of the known genes identified a number of very large introns, a number of very short intergenic distances, and at least one potentially bi-directional promoter. At least 3/4 of known genes and 1/2 of predicted genes are associated with CpG islands. For novel genes, three cases of overlapping genes are predicted. Results of these analyses illustrate some of the complexities inherent in mammalian genome organization and some of the limitations of current sequence analysis technologies. They also doubled the number of potential genes within the region.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Algorithms
  • Brain / metabolism
  • Chromosome Mapping
  • Chromosomes, Human, Pair 21 / genetics*
  • CpG Islands
  • DNA / chemistry
  • DNA / genetics
  • Databases, Factual
  • Exons
  • Expressed Sequence Tags
  • Female
  • Fetus / metabolism
  • Genes / genetics*
  • HeLa Cells
  • Humans
  • Introns
  • Placenta / metabolism
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Tissue Distribution


  • RNA, Messenger
  • DNA