Reymond et al
Nature ; 5th December 2002

The decoding of the human genome gave us the opportunity to estimate that the total number of human genes is approximately 30'000-40'000. A large number of these were not known before. Furthermore, the on-going effort to decode the genome of the mouse and its comparison with the human genome allows us to detect additional unknown genes.
The most important and pressing question now is to understand the function of the human genes; in other words we need to know what these genes exactly do during our lives, from the conception to adulthood, to death. This is a difficult task since each gene and the protein that it produces has a specific function in a specific place of the body, and at a specific time.

One way to begin searching for gene function is to determine where and when the gene is expressed. Simply, which body part (tissue) and which cell utilizes each gene; and at which specific time.

Three European laboratories (i) the Division of Medical Genetics, University of Geneva Medical School, and University Hospitals in Geneva, Switzerland, (ii) the TIGEM (Telethon Institute of Genetics and Medicine), in Naples, Italy and (iii) the Max Planck Institute of Experimental Endocrinology, in Hannover, Germany, joined their forces and expertise to collaboratively tackle this problem. They decided to focus on all the genes of the smallest human chromosome, the chromosome 21. This chromosome is of particular interest to researchers because it provides a model for all other chromosomes, and is associated with the most common cause of mental retardation, Down Syndrome.
The researchers from the three laboratories used the mouse to determine the body areas of expression of the genes. They initially focused on the developing mouse embryo at mid-gestation since most of the organs of the body are formed during that time. Then they studied these genes in a more advanced stage of embryonic development. Furthermore they looked at the expression of these genes in different tissues and body parts of the adult mouse. To perform this work, the scientists began by isolating all the mouse genes that are corresponding to the human genes on chromosome 21. This task was possible because of the decoding of the human genome, the advancements in the mapping and sequencing of the mouse genome, and the developments of sophisticated computer programs that recognize the homologous human-mouse genes.

This collaborative work, that in Geneva was directed by Professor Stylianos Antonarakis and Dr Alexandre Reymond, has produced thousands of microscopic images that show the location of the expression, (the work site), of all known mouse homologues of human chromosome 21 genes. All of these images and the interpretation of the results of this research are freely available to the scientific community via the internet.

The greatest impact of this analysis is in the assessment of the contribution of human chromosome 21 genes in Down syndrome symptoms and signs, and numerous other disorders caused by chromosome 21 genes. By knowing where a gene is expressed (works), we can predict the tissue (body part) that will be affected if this gene is mutated.

This study which is published in the prestigious scientific journal "Nature" on December 5, 2002, provides the next level of annotation of the human and mouse genomes and brings researchers closer to the answer to the most important question in genomic biology: what is the function of each and everyone of human genes. This study also provides a model for the investigation of the genes in all other chromosomes and continuous the great Academic scientific traditions of free availability of the data without restrictions to the entire scientific community. It also provided a model of successful and productive collaboration between European Laboratories.
The research in Prof Antonarakis laboratory was financed by the Swiss National Science foundation, the NCCR Frontiers in Genetics, and the "ChildCare" foundation.