The German-Japanese Consortium deciphers human chromosome 21 - A basis for comprehensive understanding of trisomy 21 (Down syndrome)

May 07, 2000

Chromosome 21 is one of the smallest among the 23 different human chromosomes. It is associated with Trisomy 21, one of the most common genetic diseases (also known as Down syndrome). An extra copy of chromosome 21 results in severely aberrant physical and mental development in children, leading to mental retardation. The disease affects up to 1 in 700 live births. An international collaborative group led by German and Japanese scientists will publish the sequence of chromosome 21 in the journal Nature (18th May 2,000). This work will be freely available on the Nature website from the 8th May. With these findings, the scientists deliver the key for a deeper understanding of the molecular mechanisms of trisomy 21 and other diseases involving chromosome 21, as well as for the design of novel diagnostic tools.

After the successful sequencing of chromosome 22 in December 1999 by a group of international scientists, chromosome 21 is now the second human chromosome which has been deciphered completely. Virtually all genes encoded by chromosome 21 have now been identified by computer-based analysis of the genomic sequence. This tremendous scientific effort was achieved by an international cooperation of scientists from 5 institutions: RIKEN genomic science center, Sagamihara (Japan), the Department of Molecular Biology of Keio University, Tokyo (Japan), the GBF-Gesellschaft fuer Biotechnologishe Forschung, Braunschweig (Germany), the Institut fuer Molekulare Biotechnologie (IMB), Jena (Germany), and the Max Planck Institute for Molecular Genetics, Berlin (Germany).

Historically, sequencing of chromosome 21 started in the early 90's. By 1995, the German-Japanese consortium was formed, with the aim of accomplishing the task of systematic sequencing of all of the 33.546.361 base pairs of chromosome 21. Altogether, a total of 170 people have worked on this international project. The German Ministry of Education and Science (BMBF) has financed the German groups with 23 million German marks over 5 years.

Based on the scientist's results, we know today that chromosome 21 contains 225 genes: 127 of them are clearly characterized genes, whereas the remaining 98 have been discovered by computer gene predictions. Scientists use the fact that characteristic structural patterns are common to most human genes as the basis of these computer methods. Computer scanning of these hallmark features in the chromosome sequence allow the researchers to identify where the coding regions are located. The function of 103 out of the 127 characterized genes is known, meaning that the corresponding protein was previously identified or that at least its activity in a defined biochemical pathway is known. The next goal for the researchers is to characterize in detail the remaining novel genes and to find their function. Some of them are associated to a number of genetic diseases mapping to chromosome 21 but for which candidate genes are still unknown: several forms of deafness, solid tumors, a form of manic depressive psychosis for instance.

A focus of interest are the 14 known genes localized on chromosome 21 for which genetic modifications are associated with severe monogenic diseases. Among these are Alzheimer's disease, a particular form of epilepsy, auto-immune conditions, and also increased susceptibility for leukaemia. Also, the gene catalogue of chromosome 21 will provide the basis for identifying candidate genes responsible for genetic diseases mapping to chromosome 21 but for which the etiology is unknown. These include for instance, two loci for deafness, a form of manic psychosis and several forms of cancer. In the context of Down syndrome, the scientists are hoping that the sequence data will provide in the future a basis for research development towards the design of novel diagnostic tests. The future expectation is to provide alternative tests to alleviate the high risk associated with amniocentesis.

A completely different matter of long debate has been the estimate of the number of genes and proteins in mammals. With a total length of 3 to 4 milliards of base pairs, the human genome could in principle encode for more than 3 millions of proteins, a figure that is, however, far too big. It has been known for a long time that the part of the genome that encodes genes lies in particular regions, whereas the rest of it is devoid of coding information meaning "a lot of base pairs but little text". The current estimate of the total number of human genes is between 80.000 and 140.000. In light of the data examined here by the scientists, the number of genes would be far below any previous estimate. By extrapolation from the number of 225 genes encoded by chromosome 21 and from the 545 genes encoded by chromosome 22, and considering the size of the human genome, the total number of human genes may be as little as 40,000.
-end-
For further information contact:
http://chr21.rz-berlin.mpg.de
http://genome.gbf.de
http://genome.imb-jena.de
http://www.dhgp.de

The Consortium:

Yoshiyuki Sakaki: RIKEN, Genomic Sciences Center, Sagamihara 228-8555, Japan;

André Rosenthal: Institut für Molekulare Biotechnologie (IMB), D-07745 Jena, Germany;

Nobuyoshi Shimizu: Department of Molecular Biology, Keio University, Tokyo 160-8582, Japan;

Helmut Blöcker: GBF - Gesellschaft für Biotechnologische Forschung, D-38124 Braunschweig, Germany;

Marie-Laure Yaspo und Hans Lehrach: Max-Planck-Institut für molekulare Genetik, D-14195 Berlin, Germany

Max-Planck-Gesellschaft

Related Genome Articles from Brightsurf:

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Breakthrough in genome visualization
Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome.

Sturgeon genome sequenced
Sturgeons lived on earth already 300 million years ago and yet their external appearance seems to have undergone very little change.

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.

Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.

Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.

A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.

How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.

Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.

Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.

Read More: Genome News and Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.