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Sequence of human chromosome 7 is fine-tuned and finished


Researchers at Washington University School of Medicine in St. Louis, in collaboration with investigators at five other centers, have finished sequencing human chromosome 7. The findings are published in the July 10 issue of the journal Nature.

Chromosome 7 is the largest human chromosome to be sequenced so far. The analysis revealed that the chromosome has about 1,150 genes and 940 so-called pseudogenes, stretches of DNA that closely resemble genes but contain some genetic change that prevents them from functioning like a gene. The biological significance of pseudogenes is unknown.

"This work completes another volume in the genome encyclopedia at a high standard of quality and a high degree of continuity," says principal investigator Richard K. Wilson, Ph.D., director of Washington University’s Genome Sequencing Center and professor of genetics and of molecular microbiology. "The sequence for chromosome 7 will be very useful for follow-up studies that have a medical application."

The work may benefit research in cystic fibrosis, deafness, B-cell lymphoma and other cancers, genes for which are found on chromosome 7. Also found there is the gene for P-glycoprotein, a protein that enables cancer cells to resist anticancer drugs. Other important genes found on chromosome 7 include those that help control cell division and cell death, genes for taste and smell receptors and those involved in immune responses.

Chromosome 7 also has a relatively centrally located centromere, a small region found on all chromosomes that is important during cell division. Centromeres on other chromosomes sequenced so far are located near the tip of the chromosome, like a knob. The centromere on chromosome 7 divides the chromosome into a short arm and a long arm, both of which carry many genes. Sequencing proceeded from each end toward the centromere.

The centromere itself contains many short repetitive DNA sequences and few, if any, genes.

"We got in close to the centromere and characterized those repeat sequences for the first time," Wilson says.

The most challenging region of the chromosome to sequence was that containing genes for Williams-Beuren syndrome (WBS), a rare genetic disorder characterized by mild mental retardation, unusual facial appearance and a narrowing of the aorta, the major artery leaving the heart. The WBS region was difficult to decipher because it contains large segments DNA with many duplicated genes, and the number of duplicated genes differs among individuals. Children with WBS are missing long stretches of these duplicated genes.

"It seems that multiple copies of these genes are necessary for normal development, and if any are lost, developmental abnormalities occur," Wilson says. "People who study this disease may find the chromosome 7 sequence data very helpful."

Next, Wilson and his colleagues will resequence certain genes on chromosome 7 from people with acute leukemia to better understand the genetic changes that give rise to the malignancy.

Hillier LW, Fulton RS, Fulton LA. et al. The DNA sequence of human chromosome 7. Nature, July 10, 2003.

Darrell E. Ward | EurekAlert!
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