Genetic Deformities Linked to Schizophrenia

(November 25, 2006) -- The genetic recipe for humans turns out to be far more complicated than imagined, with some perfectly normal people carrying multiple copies of some genes while others are missing huge chunks of DNA.

The realization, which has shocked geneticists, overturns the long-held notion that children inherit a single copy of each gene from their parents.

An international team, co-led by Stephen Scherer of the Hospital for Sick Children in Toronto, has shown it is common for people to have large blocks of missing or extra DNA, often covering several different genes.

"There are people walking around with millions of nucleotides more or less DNA than the guy on the subway next to him," says Scherer. "It's really astounding." Nucleotides are the molecular building blocks of DNA and genes, which form the basis of heredity.

Scherer and his colleagues report in the journal Nature today how close to 1,500 regions, comprising almost 10 per cent of all human genes, are impacted by deletions and extra copies. Some genes, such as one involved with an enzyme in saliva that helps break down carbohydrates, always come in multiples. Some people have 10 copies of the gene, while others have 30, says Scherer.

Scientists have long known differences in DNA makes each individual unique. But until now, they have likened the differences to typos, or spelling differences in the book of life. The new reports "show that it's not only single letters but sentences, paragraphs, and even whole pages that can be missing or duplicated," say researchers at the Wellcome Trust Sanger Institute in Britain who collaborated on the project.

While much of the variation is normal and harmless, there is growing evidence missing and multiple gene regions can cause significant problems. Not only can they cause serious congenital and developmental deformities in children, but they now appear to play a role in Alzheimer's, heart disease, Parkinson's disease, schizophrenia and even susceptibility to HIV infection. People with extra copies of a gene called CCL3L1 have increased resistance to HIV infection.

The scientists say the realization there is so much variation in the human genome will transform understanding of many disorders and diseases. Until now, medical sleuths have spent much of their time -- and hundreds of millions of dollars -- searching for single gene mutations, or typos in individual genes, to try to explain why some people and families are more prone to diseases than others.

While single gene mutations do cause conditions like Huntington's disease, Scherer says extra and missing chunks of genetic material appear to be even more important and prevalent than mutations. He notes how one gene associated with Alzheimer's only causes problems when people have three copies instead of two.

He says researchers had their blinkers on when they announced in 2001 they had cracked the human genome, an enormous sequence of DNA containing about three billion nucleotides. They suggested people were 99.9 per cent identical genetically, and failed to mention the phenomenon of missing and multiple gene regions that have now been shown to affect 2,900 genes, close to 10 per cent of the estimated 30,000 genes on the genome.

Scherer says there were clues pointing to the phenomenon in the late 1990s, but few scientists involved in the race to sequence the human genome were aware of them. Even if they had been, he says techniques were not available to map the variations.

Scherer says it took his team, which includes researchers at leading gene labs in Europe, the U.S. and Japan, just months to comb through the DNA of 270 people with Asian, African and European ancestry and map the region's affects by copy number variants or CNVs.

They found 1,477 regions, often covering more than one gene, vary in the number of copies. And this is "probably the tip of the iceberg," Huntington Willard, director of the Institute for Genome and Science Policy at Duke University, writes in a Nature commentary, noting it is essential that researchers catalogue the full range of CNVs.

advertisement

Dr. James Lupski, a leading geneticist at Baylor College, in Texas, predicts the discovery "will change forever the field of human genetics."

Scherer agrees, and says the team has posted a detailed map of the variable DNA regions on the Web. He says researchers need to look at the big picture, including multiple and missing DNA segments, when searching for genetic explanations for variations in disease susceptibility.

By Margaret Munro
Source: CanWest News Service

Last updated: 10/06

top ~ next ~ news table of contents ~ send page to a friend

We subscribe to the HONcode principles. Verify here.