Researchers Break Code on Chromosome


An international team of scientists has deciphered the genetic code of an entire human chromosome for the first time--a major milestone in the public effort to decode in detail all of the chromosomes that make up the human genome.

Publishing their results in today’s issue of the scientific journal Nature, researchers from England, Japan and the U.S. say they have completed the decoding work on chromosome 22, the second-smallest of the human chromosomes, but still a sizable volume in what has been called the encyclopedia of human life.

The payoffs for decoding the human chromosomes are expected to be enormous in predicting, diagnosing and treating human ailments such as cancer, arthritis and heart disease and perhaps in being able to forestall the effects of aging.


Chromosome 22 contains genes thought to play a role in immunity, heart disease, schizophrenia, mental retardation and several cancers, including a form of leukemia. The detailed sequence of the chromosome should help to explain cat-eye syndrome, a form of retardation, and DiGeorge syndrome, which causes facial deformities and immune deficiencies. Knowing the sequence will almost certainly lead to a deep understanding of what goes awry in these diseases--and should allow biotech and pharmaceutical companies to develop new medications to treat them.

The scientists painstakingly determined the order of the 33 million chemical building blocks linked together in a long molecule of DNA that runs through the chromosome. Printing out the exact sequence of these compounds in chromosome 22, using the letters A, T, C or G to stand for the chemicals adenine, thymine, cytosine and guanine, would fill a large telephone book.

The researchers could not include the full code itself in their Nature paper, but a complete version is available on the Internet ( or

In reading out the chromosome’s DNA, the researchers found evidence of between 600 and 1,000 genes scattered across it. Although the chromosome has been heavily studied, hundreds of these hereditary units were unfamiliar, their purpose unknown. The scientists also found more than 100 pseudo-genes, evolutionary remnants that may have no function at all in humans. And there were several long duplications, which could explain a number of inherited disorders.

The scientists make clear that this new book of information, covering just one of the 23 pairs of chromosomes at the center of virtually every human cell, is just a beginning--an important step in a decade-long effort paid for by the U.S. and other governments and Great Britain’s Wellcome Trust, one of the world’s wealthiest charities. But there is still a sense of awe surrounding the accomplishment.

“To see the entire sequence of a human chromosome for the first time is like seeing an ocean liner emerge out of the fog, when all you’ve ever seen before were rowboats,” said Dr. Francis Collins, director of the National Human Genome Research Institute, which funded the U.S. portion of the work.


Despite the congratulatory air, the researchers are very much aware that they are in competition with private companies anxious to claim the territory as their own property.

In particular, Maryland-based Celera Genomics is racing to finish the genome ahead of the public effort and has already filed provisional patents on 6,500 novel human genes. What makes that remarkable is that the company only began sequencing the human genome in September, using 300 high-speed sequencing machines produced by its sister company, PE Biosystems.

In a commentary accompanying today’s publication, one scientist wrote that “it would be a terrible blow for science and humanity if the human genome became a commercial property.” To keep that from happening, scientists in the international consortium have agreed to make their work freely available on the Internet within 24 hours of completing the sequence for each small piece of DNA.

The underlying competition did not diminish the celebratory mood Wednesday, when government officials and scientists officially announced the achievement.

“Now we can begin to understand where genes are located on chromosomes, how they express themselves, how deletions that give rise to disease-causing mutations occur, and how chromosomes are duplicated and inherited,” said Bruce Roe of the University of Oklahoma, one of several centers around the world, including Caltech in Pasadena, where the sequencing of chromosome 22 was conducted.

“This immediately suggests new experiments and avenues of research which can be pursued,” said Ian Dunham, who led a team at England’s Sanger Centre.


But the scientists also discovered the limits of the methods developed over the last 15 years to decipher the genetic code. The researchers reported 11 gaps along the chromosome--stretches that they could not read using the latest techniques available. These relatively short stretches contain large numbers of repeated sequences. The purpose of these sections of the chromosome are still not understood, but it is generally accepted that the sequence can be considered essentially complete without them.

The genome institute’s Collins said researchers knew ahead of time that there would be such gaps and set a standard for what would count as “operational” completeness for any chromosome. “We anticipated that there might be lots of them,” he said. “That there were only 11 of them was reassuring.” It might take another 10 years to fill in the missing stretches, he said, less than 3% of chromosome 22.

In assembling all the pieces of the chromosome into one consecutive whole, the scientists were faced with a problem much like putting together a jigsaw puzzle that has thousands of nearly identical pieces--if these “repeats” are all alike, it is very difficult to know exactly which piece goes where.


Decoding a Human Chromosome

Researchers have deciphered virtually the entire genetic pattern of the first human chromosome. Below, a look at some of the genes that map to regions on chromosome 22.


Sources: Associated Press, University of Oklahoma



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