A new way of comparing DNA has turned up surprising genetic differences among normal, healthy people, researchers said on Thursday.
The researchers found — by accident — that some people are missing large chunks of DNA, while others have extra copies of stretches of DNA.
Writing in the journal Science, the researchers have dubbed these differences “copy number polymorphisms.” They are found in genes linked with cancer risk, with how much people eat and with reactions to drugs.
“Thus, a relationship between CNPs and susceptibility to health problems such as neurological disease, cancer, and obesity is an intriguing possibility,” the researchers wrote in their report.
New DNA test used
The team at Cold Spring Harbor Laboratory in New York, the Karolinska Institute in Stockholm, Sweden and elsewhere used a new kind of DNA test called Representational Oligonucleotide Microarray Analysis or ROMA.
“It can detect differences in DNA from any two sources,” said Cold Spring Harbor spokesman Peter Sherwood.
The researchers were looking for genetic differences linked with cancer.
“As a control in the cancer experiment they compared normal to normal DNA, expecting it to be pretty much the same,” Sherwood said in a telephone interview.
“They detected more than 70 of these large chunks of DNA that were altered in normal human cells.”
These were large differences that have not been reported before — involving much more DNA than so-called single nucleotide polymorphisms, which are well-known single-letter changes in the A, C, T, G nucleotide code that makes up DNA.
“They looked at blood and normal tissues from 20 people from different geographical regions. They found that probably on average about five of the people would have the same difference, the same CNP,” Sherwood said.
Mistakes in genome map?
Everyone has two copies of each chromosome, except for the X and Y chromosomes that separate men from women. The researchers found that each of their healthy volunteers had just one copy of each CNP.
“If they happen to marry and have children with someone who has the same CNP, maybe the children will be affected,” Sherwood said.
The researchers also found possible mistakes in the map of the human genome published by the Human Genome Project.
In 20 people they found a stretch of DNA on chromosome 16 that does not appear there in the published sequence of the human genome — but rather on chromosome 6. “It is extra copies of a gene that no one knew about,” Sherwood said.
Comparisons of human to chimpanzee genomes have found similar swaps, when a gene migrates from one chromosome to another.
“Just as chromosomal rearrangements have played a significant role in primate evolution and human disease, structural polymorphisms may play an analogous role in determining genetic diversity within the human population,” the researchers wrote.
Some of the CNPs, the researchers said, were found in unstable genetic regions where reshuffled genes are associated with conditions such as Prader-Willi and Angelman syndromes, cat eye syndrome and spinal muscular atrophy.
“These CNPs are not directly implicated in the above diseases, but they may reflect the instability of these genomic regions,” they wrote.
