School of Medicine researchers, in collaboration with investigators at seven other centers, have finished sequencing human chromosome 7 — the largest human chromosome to be sequenced yet.
The findings were published in a recent issue of the journal Nature.
The analysis revealed that the chromosome has about 1,150 genes and 940 so-called pseudogenes, or 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,” said principal investigator Richard K. Wilson, Ph.D., director of the 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 cancer genes that are found on chromosome 7. The gene for P-glycoprotein, a protein that enables cancer cells to resist anticancer drugs, is also found there.
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. Centro-meres on other chromosomes sequenced so far are located near the tip of the chromosome.
The centromere on chromosome 7 divides the chromosome into a short and 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 said.
The most challenging region of the chromosome to sequence was the area that contains 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 of 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 said. “People who study this disease may find the chromosome 7 sequence data very helpful.”
Next, Wilson and his colleagues will re-sequence certain genes on chromosome 7 from people with acute leukemia to better understand the genetic changes that give rise to the malignancy.