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Two international research consortia marked major milestones in the Human Genome Project (HGP) with the completion of the first high-quality DNA sequences for two human chromosomes. Chromosomes 22 and 21 sequences, respectively, were reported in the December 2, 1999, and May 18, 2000, issues of Nature. These two chromosomes, smallest in the human genome, account for 2% to 3% of the total 3 billion DNA bases.
Chromosome 22
Chromosome 22's euchromatic (gene-containing) portion is estimated to be a 33.5-Mb structure comprising at least 545 and possibly up to 1000 genes ranging in size from 1000 to 583,000 bases. Genes are pinpointed by their sequence similarities to those already identified in other organisms and by complex computer modeling of potential (putative) genes that may be only partially accurate. Chromosome 22's sequenced DNA is of extremely high quality with an error rate of less than 1 in 50,000 bases.
Gene variants on chromosome 22 have been implicated in immune system function and in at least 27 disorders, including congenital heart disease, schizophrenia, mental retardation, birth defects, and leukemia and other cancers. Scientists reported that at least eight regions are present in duplicate, leading to speculation about this phenomenons evolutionary importance. Duplication can be studied closely when comparable animal genome sequences become available.
Chromosome 21
Chromosome 21 revealed a relatively low gene density, estimated at about 225 active genes in the 33.8 Mb of DNA covering 99.7% of the chromosomes long arm. Scientists speculate that this gene scarcity could contribute to the viability of individuals possessing a third copy of the chromosome, resulting in trisomy 21 (Down syndrome). The sequence also includes a contig of 28.5 Mb, the longest continuous DNA sequence reported thus far. The entire sequence has only 3 gaps totaling about 100,000 bases, compared with 10 gaps (totaling about 1Mb) for chromosome 22's long arm.
Analysis of chromosome 21 genes may permit a deeper understanding of Down syndrome and its complications, as well as a range of such other linked genetic disorders as Alzheimers disease and some forms of cancer. |
| Author: Aaron Hall |
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