The DNA Sequence and Analysis of Human Chromosome 14 Completed
Institute for Systems Biology Researchers Make Significant Contribution to Effort

Seattle – Wednesday, January 1, 2003 -- The Institute for Systems Biology (ISB), a non-profit research institute dedicated to the study and application of systems biology announced today that the Institute and two other laboratories have completely sequenced Chromosome 14 as part of the Human Genome Project.

The group at the Institute for Systems Biology, led by Dr. Leroy Hood and Dr. Lee Rowen, was responsible for mapping and sequencing about 10% of the chromosome, in an effort that extended more than three years and involved about 20 research scientists.

“The draft sequences of the human genome have provided voluminous amounts of information to the biomedical community regarding the identification of genes involved with human disease,” stated Dr. Lee Rowen, senior scientist at the Institute for Systems Biology. “However, gaps and inaccuracies in the draft sequences have inhibited our ability to fully leverage the information as it relates to ongoing research efforts in predicting and preventing disease.

“The completion of the sequencing of chromosome 14 represents a major step forward in obtaining high quality, accurate information and ultimately a better understanding of how specific genes relate to diseases,” stated Rowen. About 60 disease genes have been associated with chromosome 14, including one that predisposes to the early onset of Alzheimer’s disease. Several types of leukemia and tumors have also been associated with rearrangement of specific regions of chromosome 14.

Chromosome 14 is the fourth chromosome to be finished, the largest to be analyzed so far, and the only chromosome for which there are no gaps in the final sequence. The length of the contiguous sequence is 87,410,661 nucleotides, representing about 3% of the entire human genome. Careful studies were performed to ensure the validity of the sequence.

Chromosome 14 contains about 500 known genes and an additional 350 putative genes, whose function is yet unknown. Particularly noteworthy genes on chromosome 14 include the alpha/delta T cell receptor loci, sequenced by the Hood laboratory in the mid-
90s, and the immunoglobulin heavy chain region. These loci are essential parts of the
adaptive immune system responsible for recognizing foreign invaders such as bacteria and viruses and mounting a protective immune response. Chromosome 14 also contains
an enzyme called "telomerase", which is thought to play a role in preventing the ends of chromosomes from being degraded and thereby protecting the chromosomes against aging.

One of the most interesting genes on 14 is neurexin 3, a gene that spans about 1.7 million bases, which is approximately 30 times greater than the average size of genes on chromosome 14. Because of a process called "alternative splicing," this gene exists in potentially thousands of different minor variations which may play a role in its function, which is currently believed to be neurological. While no one knows exactly what neurexin 3 gene does for sure, it is thought to play a role in making synaptic connections in the brain.

The human genome project, scheduled to be completed by April 2003, aims to delineate all of the genes in the human genome so that their functions can be understood better and correlations between specific variations in the genes’ sequences and observable effects such as physiological and behavioral traits and disease susceptibilities can be made. With improved knowledge, drug design can be more appropriately targeted and therapies better tailored to individual patients.

The other participating groups in the Chromosome 14 Project include Genoscope, the National Sequencing Center of France, and the Genome Sequencing Center at Washington University at St. Louis.

A report entitled "The DNA Sequence and Analysis of Human Chromosome 14" is scheduled to be published in this week’s issue of Nature (www.nature.com) for release at 2:00 p.m. PST Wednesday, January 1, 2003.

About the Institute for Systems Biology
The Institute for Systems Biology (ISB) is an internationally renowned non-profit research institute dedicated to the study and application of systems biology. ISB's goal is to unravel the mysteries of human biology and identify strategies for predicting and preventing diseases such as cancer, arthritis and AIDS. The driving force behind the innovative "systems" approach is the integration of biology, computation, and technology. This approach allows scientists to analyze all of the elements in a system rather than one gene or protein at a time. Located in Seattle, Washington, the Institute has grown to more than 170 faculty and staff members, and has an extensive network of academic and industrial partners.