Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gene-rich human Chromosome 19 sequence completed


The United States Department of Energy (DOE) Joint Genome Institute (JGI) and Stanford University report today the completion of the sequencing of human chromosome 19, the most gene-rich of all the human chromosomes. This achievement is described in the April 1, 2004 edition of the journal Nature.

“Culminating 18 years of research, this partnership exemplifies DOE’s commitment to advancing our understanding of the complex interplay between our human health and the environment,” said Energy Secretary Spencer Abraham, whose agency funded the work through its Office of Science.

Embedded in this sequence information are critical regulatory networks of genes tasked with controlling such functions as repairing DNA damage caused by exposure to radiation and to other environmental pollutants. Studies of DNA-repair genes, initiated at the DOE National Laboratories, are yielding insights into the development of certain cancers, many of which appear to be caused by defects in DNA-repair pathways. Also, new insights are being gleaned about other gene families implicated in detoxifying and excreting chemicals foreign to the body.

“With this high-quality sequence now made freely available to the scientific community, more light will be shed on individual responses to medicines,” Abraham said. “This will enable the development of more sensitive diagnostics for susceptibility to a wide array of important diseases. In time, with this information in hand, physicians will be able to tailor more effective individualized therapeutic strategies.”

Chromosome 19, at 55.8 million bases or letters of genetic code, although representing only about 2% of the human genome, features nearly 1,500 genes. They include genes that code for such diseases as insulin-dependent diabetes, myotonic dystrophy, migraines, and familial hypercholesterolemia (an inherited form of elevated blood cholesterol), which increases the risk of cardiovascular disease. “Beyond the significant revelation that chromosome 19 has more than twice the gene density of the genome-wide average, it also offers a fertile landscape for exploring evolutionary motifs,” said JGI Director Eddy Rubin. “An intriguing picture has emerged regarding conservation and divergence, revealing large blocks of gene conservation with rodents as well as segments of coding and noncoding conservation with more distant species such as the pufferfish, Fugu rubripes, which was also sequenced here at the JGI. While not long ago these noncoding regions were considered nonsense, now they are actually proving to have powerful regulatory influence over the genes that they bracket.”

The DOE originally selected chromosome 19 as a sequencing target because of the agency’s abiding mission of investigating the link between DNA damage from radiation exposure and human cancer. Initial work conducted by Lawrence Livermore National Laboratory in the mid 1990s led to the mapping of multiple DNA-repair genes on chromosome 19. In 1999, the sequencing and finishing projects were transferred to the JGI and the Stanford Human Genome Center, respectively.

“Unlike earlier draft human genome sequences, this version is 500 times better in terms of contiguity and accuracy—which makes a huge difference if you are trying to do biology with that sequence,” said Richard Myers, Director, Stanford Human Genome Center. “It gives you a sense of the chromosome’s topography—one filled with such biologically interesting features as transcription factors, olfactory receptor genes, and zinc finger genes.”

Olfactory receptors represent the largest multigene family in higher organisms. They have evolved in response to the need for animals to recognize millions of odors—both threatening and attractive—in their environment. Transcription factors are proteins that need to be recognized by RNA polymerase in order to initiate the elaboration of nucleotides along the DNA molecule. Zinc finger proteins are chains of amino acids that capture a zinc ion and bind to RNA or DNA and play a critical role in a cell’s life cycle. These proteins regulate the expression of genes as well as nucleic acid recognition, reverse transcription, and virus assembly. Drug development efforts seek to disrupt these zinc finger structures to prevent viruses from functioning.

Chromosome 19, however, was not without its challenges, Myers added. “The sequence was harder to work through than expected. It was highly repetitive, with high GC content. It’s a real tribute to this team that they could get the sequence finished.”

Stanford’s role in the collaboration is the critical one of “finishing” the DNA sequence. The finishing process ensures that the information made available through the public databases is completely contiguous, with all ambiguities resolved. This painstaking process begins with the electronic transmission of draft data sets, some 20 billion bytes per week, and shipping of bacteria culture plates from the JGI’s Production Genomics Facility in Walnut Creek, California, to Stanford.

“To get this level of confidence several iterations of the genome sequence is required, typically at six to eight times coverage,” Myers said. In areas that fail to meet the required quality standard, directed finishing reactions of many different types are performed and the resulting data incorporated back into the draft assembly. Only after rigorous scrutiny, when all data has been extensively reviewed by a human finisher, and all gaps and low-quality areas have been resolved, will the sequence data be posted in the public databases. The quality of the finished chromosome 19 sequence far exceeds the 1 in 10,000 base pair error rate set by the International Human Genome Sequencing Consortium, with the error rate estimated to be much less than 1 in 100,000 base pairs.

“The JGI-Stanford partnership has been integral to the timely and economical completion of chromosome 19,” JGI Director Rubin said. “DOE’s contribution to sequencing the human genome totals some 11%, with chromosome 19 representing the first of the three chromosomes the team has tackled, together with the completion of Chromosomes 16 and 5 in the offing.” The magnitude of the accomplishment is further reflected in the nearly one hundred authors cited on the paper led by Jane Grimwood at Stanford and Susan Lucas at the JGI. Other authors include investigators at Lawrence Livermore and Los Alamos National Laboratories; University of California, Santa Cruz,;Children’s Hospital Oakland, California; the Howard Hughes Medical Institute at the University of Washington, Seattle; Case Western Reserve University; and the National Cancer Institute.

The Joint Genome Institute (JGI), located in Walnut Creek, California, was established in 1997 by three of the DOE national laboratories managed by the University of California: Lawrence Berkeley National Laboratory and Lawrence Livermore National Laboratory in California and Los Alamos National Laboratory in New Mexico. In addition to its human genome sequencing activities, JGI has whole genome sequencing programs devoted to other vertebrates, microbes, and plants. Funding for the JGI is predominantly from the Office of Biological and Environmental Research in DOE’s Office of Science. Additional information about the JGI is available at

The Stanford Human Genome Center (SHGC) is part of the Department of Genetics at Stanford University. SHGC, originally funded as a pilot sequencing center for the human genome project, is currently involved in a variety of scientific research programs, including large-scale genomic finishing, human disease linkage studies, vertebrate diversity, and the elucidation of functional sequence elements in the human genome. Additional information about the SHGC is available at

David Gilbert | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>