Sequence of human chromosome 7 completed

By completing the gene sequence of human chromosome 7, scientists have discovered an unusually high degree of segmental duplication, associated with pathological and evolutionary instability.

Dr. Richard K. Wilson, of Washington University School of Medicine in St. Louis, and other members of the International Human Genome Sequencing Consortium describe their analysis in the July 10th issue of the journal Nature. They report that they have sequenced 99.4% of the gene-containing region of chromosome 7 to an accuracy of greater than 99.99%.”For the first time, we’ve really sorted out pseudogenes from functional protein-coding genes for a large chromosome,” Dr. Wilson told Reuters Health. He explained that pseudogenes are prevented from being transcribed into mRNA or translated into protein. For example, “they may have a stop codon in the middle of the reading frame, or a small deletion that doesn’t allow it to be spliced the way it is supposed to be.””We don’t know if they were once functional genes that somehow accumulated a sequence change that rendered them nonfunctional–the more likely scenario–or if they’re the beginnings of new genes that, when appropriate changes are made to the underlying sequence, will become functional and perhaps provide some new advantage to the organism,” he added.The group found that 7.0% of the chromosome 7 genome shares sequence homology to other areas on the same chromosome and 2.2% to locations on other chromosomes.”In some cases we see a functional copy of the gene in segment 1 and a pseudogene at the same place in segment 2,” Dr. Wilson said. “The question is, did they both start as pseudogenes and one became functional, or visa versa?” He noted that there is “decent evidence” that duplicated genes sometimes mutate until the encoded protein evolves a new function.Some duplicated sequences become “hot spots” for congenital disorders, such as Williams-Beuren syndrome, or oncogenic processes.The Consortium is now analyzing the sequences for human chromosome 2 and 4. “We’re also sequencing the chimpanzee and chicken genomes to better understand the human sequence,” Dr. Wilson continued, “and we’ve started resequencing DNA of genes involved in leukemia.”(Source: Nature 2003;424:157-164: Reuters Health: Karla Gale: July 9, 2003: Oncolink)