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Down Syndrome Research Expedited by Decoding of Human Chromosome 21 - Second Human Chromosome Sequenced by the Human Genome Project

May 2000

BETHESDA, Md. - Scientists in Japan and Germany will report in an upcoming issue of Nature that they have unraveled the genetic code of human chromosome 21, already known to be involved with Down syndrome, Alzheimer's disease, Usher syndrome and Lou Gehrig?s disease.

It is the second human chromosome whose DNA has been fully deciphered by the Human Genome Project (HGP), the international consortium of scientists dedicated to spelling out, or sequencing, the 3 billion chemical letters of human DNA. These scientists are providing that data immediately at no cost and without restrictions to all scientists in industry and academia. Chromosome 22 was the first human chromosome to be sequenced. An international collaboration of HGP scientists reported on that milestone in the Dec. 2, 1999 issue of Nature.

The DNA sequences of both chromosomes are ?finished.? The sequence data is highly accurate - since each area of the chromosome has been ?read? about nine times. The only gaps in the sequence are areas of the chromosome that cannot be deciphered or ?read? with current technology. The scientists have identified the location and size of each of the gaps.

Dr. Francis Collins, director of the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH), applauded the scientists who sequenced chromosome 21, for their achievement.

?Knowing the DNA script of chromosome 21, scientists are better equipped to answer the many questions about the origins of Down syndrome, Alzheimer's disease and other disorders,? said Dr. Collins. People who are born with Down syndrome, characterized by varying degrees of mental retardation, heart defects and immune system deficiencies, have an extra copy of chromosome 21. Most people have two copies of each chromosome. People with Down syndrome have three copies of this chromosome.

?Why does having three copies of chromosome 21 cause Down syndrome? And why are some people with Down syndrome minimally affected, while others are more severely retarded?

?By looking at the organization of the genes on chromosome 21 and how they and their protein products function, scientists can find clues about Down syndrome as well as other disorders, including Alzheimer's disease, certain cancers and manic depressive illness, which have also been linked to this chromosome,? he added.

Each human gene is made up of a series of chemical building blocks represented by letters, A (adenine), T (thymine), G (guanine) and C (cytosine). The number and order of these letters, also called bases, determine the genetic contribution to what we are, how we look and the diseases to which we may be predisposed.

With the complete sequence of chromosome 21 available, scientists can better understand where genes are located on the chromosome, how they are expressed, how changes that give rise to disease-causing mutations occur, and how chromosomes are duplicated and inherited.

With the complete DNA sequence of multiple chromosomes in hand, scientists can study structural similarities between and among chromosomes, as well as shared sequences.

In deciphering chromosome 21, scientists used the strategy that has been developed and widely tested by the Human Genome Project. This strategy involves sequencing overlapping cloned segments of DNA from known locations on the chromosome. Because they know the areas of the chromosomes that are represented in the overlapping clones, the scientists can accurately take the sequence of thousands of A, T, C and Gs that was ?read? from each clone, lay out the data according to locations of the individual clones on the chromosomes and in that way reconstruct the sequence of the entire chromosome.

The Human Genome Project will compile a finished, ?stand the test of time? version of the DNA sequence of all 23 pairs of human chromosomes by 2003 or sooner. A ?working draft? version of the sequence already is 85 percent complete. That data is 99.9 percent accurate based on reading each area of the chromosome four to five times.

Cathy Yarbrough

April Thompson

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Last updated: September 01, 2006