September 15, 2011
(Ivanhoe Newswire) -- A chromosomal "catastrophe" that occurs early in development may be to blame for some cases of developmental delay or cognitive disorders, according to new research.
Investigators from Baylor College of Medicine analyzed the DNA of 17 patients who were referred to their center because of unexplained developmental problems. "Four were very complex," Dr. Pengfei Liu, a graduate student at BCM, was quoted as saying. "One had 18 rearrangements in one chromosome. It was beyond our imagination."
A group of British researchers published a paper around that time that described massive genomic rearrangements in cancer that they believe emanated from a single catastrophic event. The BCM researchers wondered if a similar situation had occurred in their patients, whose rearrangements happened early in the germ line -- the cells that produce eggs and sperm. The events that had occurred in the genetic code of their patients shared striking similarities to the patients with cancer.
"First, the patients have many duplications and deletions," James R. Lupski, vice chair of molecular and human genetics at BCM, was quoted as saying.
"We used comparative genomic array hybridization, FISH (fluorescent in situ hybridization, which can tell a person how many copies of a certain chromosome exist in each cell) and other techniques to demonstrate that this 'catastrophe' phenomenon exists in the genomes of these patients," Liu said. "This chromosomal catastrophe occurs not only in cancer but can also occur in different developmental tissues. They may occur in the germ line, as in our case, or in the somatic cells. In one case, the patient had this complex rearrangement, and the mother also has it, but the rearrangement occurs in only a subset of her cells. It occurred in the mother during development and she then transmitted the rearrangement to the child."
The BCM researchers say the genomic changes they describe occur early in the development. The cancer changes occur in the cells of people who are often adults.
"We are looking for the mechanisms that cause this catastrophe," Lupski said. "We are dealing with pure rearrangement. The whole body has it, not just a subset of cancerous cells within a growing tumor."
The BCM team saw features that suggested the catastrophe may have occurred as a result of a single event involving DNA replication -- the process during cell division in which the pattern of DNA is copied for use in the new cell. If that replication process misfires, the DNA is not copied accurately, and the resulting cell is abnormal.
SOURCE: Cell, September, 2011