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.

The complete DNA sequence of the A2 strain of polyoma virus has been determined. It consists of 5,292 base pairs. The sequence is analysed in terms of its coding potential and sites of possible functional significance or structural interest. The polyoma virus genome is compared with those of related tumour viruses, simian virus 40 and BK virus.

We have constructed the physical map of the 0.8 megabase DNA fragment which contains the 3' 64 variable region (V) gene segments of the human immunoglobulin heavy chain (H) locus. The organization of the VH locus showed several features that indicate dynamic reshuffling of this locus. The sequenced 64 VH segments include 31 pseudogenes, of which 24 are highly conserved except for a few point mutations. Comparison of the 64 germline VH sequences shows that each VH family has conserved sequences, suggesting that there might be some genetic or selection mechanisms involved in maintenance of each family. The total number of the human VH segments was estimated to be about 120, including at least 7 orphons.

The intensely studied MHC has become the paradigm for understanding the architectural evolution of vertebrate multigene families. The 4-Mb human MHC (also known as the HLA complex) encodes genes critically involved in the immune response, graft rejection, and disease susceptibility. Here we report the continuous 1,796,938-bp genomic sequence of the HLA class I region, linking genes between MICB and HLA-F. A total of 127 genes or potentially coding sequences were recognized within the analyzed sequence, establishing a high gene density of one per every 14.1 kb. The identification of 758 microsatellite provides tools for high-resolution mapping of HLA class I-associated disease genes. Most importantly, we establish that the repeated duplication and subsequent diversification of a minimal building block, MIC-HCGIX-3.8 -1-P5-HCGIV-HLA class I-HCGII, engendered the present-day MHC. That the currently nonessential HLA-F and MICE genes have acted as progenitors to today's immune-competent HLA-ABC and MICA͞B genes provides experimental evidence for evolution by ''birth and death,'' which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families.

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We have constructed the physical map of the 3′ region of the human immunoglobulin heavy chain variable region (VH) genes. DNA segments extending to 200 kb upstream of the JH segment were isolated in two YAC clones. Five VH segments were identified in this region in the 5′ to 3′ order, V(II‐5), V(IV‐4), V(I‐3), V(I‐2), and V(VI‐1) segments which were all structurally normal and orientated in the same direction as the JH segments. From DNA of a different cell line we have isolated a cosmid contig containing the same DNA region which has extraordinary polymorphism. The YAC and cosmid DNAs were called haplotypes A and B, respectively. Haplotype B contained an additional VH‐I segment (V(I‐4.1b)) between the V(II‐5) and V(IV‐4) segments. V(I‐4.1b) segment is almost identical to a previously published VH sequence encoding a rheumatoid factor. Another VH segment in the B haplotype (V(I‐3b)) corresponding to the V(I‐3) segment also showed 99.7% nucleotide sequence homology with an anti‐DNA autoantibody VH sequence. However, none of the VH sequences in haplotype A showed such strong homology with autoantibody VH sequences. The results suggest that VH haplotypes may have linkage with autoantibody production.