Each person's genetic makeup differs far more than previously known

Each person's genetic makeup differs far more than previously known
study Published: Wednesday, November 22, 2006
Canadian Press: SHERYL UBELACKER

http://www.cbc.ca/cp/health/061122/x11229A.html
TORONTO (CP) - Scientists have long known that each person on the planet is unique because of individual variations in what is primarily a shared genetic profile. But a groundbreaking new discovery by Canadian-led international researchers has proven these variations are far more extensive than ever anticipated.

In fact, whole chunks of DNA can differ between individuals, the scientists say.

The discovery has led to the first map of these genetic variations - and a more sophisticated tool for pinpointing the causes of both rare and common diseases that afflict humankind.

"We didn't know about this form of variation two years ago," said Dr. Stephen Scherer, director of the Centre for Applied Genomics at the Hospital for Sick Children in Toronto and a co-principal investigator of the research. "And now for the first time we've got a catalogue of information and we've been able to understand the properties of this new type of variation."

"So then we can really focus our studies and apply this information to genetic disease studies."

That means scientists around the world now have a new technique to help them home in on the genetic underpinnings of rare inherited diseases as well as those of more common disorders, such as diabetes, heart disease, various cancers, Alzheimer's and Parkinson's.

What the researchers found, in essence, is that a person's DNA does not contain just two sets of genes, one from each parent, but also on occasion multiple copies of one or more genes and some that are missing altogether. These extra or missing parts of the genome are called "copy number variations," or CNVs.

The map of CNVs was created after researchers scanned genetic material from 270 people with ancestry from Europe, Africa and Asia. State-of-the-art micro-array machinery allowed them to isolate DNA segments that previous technology was not refined enough to detect.

While that analysis confirmed that humans share much of the same DNA, it also found that the amount of variation among humans is "huge" - an estimated 12 per cent of any person's genetic material.

"We found on average about 100 of these large-scale changes in each genome we looked at," said Scherer. "I was really so surprised to see that . . . It was something that we and probably everyone else did not expect."

The human genome, often dubbed the Book of Life, is made up of about three billion letters (chemical base-pairs called nucleotides). Each of its 30,000 pages (or 30,000 genes) contains about 100,000 letters each. Previously it was believed that genetic variations among individuals occurred because of alterations in single letters that changed the "spelling" of words.

But the new work shows that variations - whether additions or deletions - affect not only single letters, but also sentences, paragraphs and even whole pages.

"And now we're seeing in some cases that you get only one page, in some cases you get three, in some cases you get four, and in rare cases you have zero," said Scherer. "Some genes or some pages of the encyclopedia are absolutely missing."

The research, which involved investigators from Canada, the United States, Europe and Japan, is causing a huge buzz in the scientific community, Dr. Tom Hudson, interim head of the McGill University and Genome Quebec Innovation Centre, said from Montreal.

"It's very exciting," said Hudson, calling it a "big new step" for medical genetics.

Different aspects of the research, appear in four papers published this week in Nature and its associated journals.

"I believe this paper will change forever the field of human genetics," James Lupski, vice-chair of molecular and human genetics at Baylor College of Medicine in Houston, Texas, said in a release.

Dr. Matthew Hurles of the Wellcome Trust Sanger Institute in Cambridge, England - Scherer's co-principal investigator on one of the papers - agreed that the extent of genetic variation from one person to the next came as a surprise.

"The copy number variation that researchers had seen before was simply the tip of the iceberg, while the bulk lay submerged, undetected," Hurles said in a statement. "We now appreciate the immense contribution of this phenomenon to genetic differences between individuals."