The major medical reason for the completion of the sequence (reading) of the
entire human genome is to discover the mutations that either cause human genetic
diseases or predispose to the development of these disorders.
To find this out scientists need to identify/recognize all the genes contained in the genome. This difficult task is facilitated by the comparison of two evolutionarily related genomes, these of human and mouse, because important DNA elements are similar between these two species.
The scientists of the Division of Medical Genetics of the University of Geneva Medical School with the assistance of members of the Swiss Institute of Bioinformatics in Lausanne, compared all the letters of chromosome 21 in human and the corresponding part of the mouse genome. They discovered something unexpected : most of the important part of genetic material (DNA) that has functional significance and is therefore almost identical between human and mouse is not the genes ! This observation has profound implications in the study of genomes and the identification of mutations involved in human disorders. The exact role of these non-gene, but important genomic elements is unknown but probably regulate the function of genes (when, where, and how a gene functions) or provide the necessary structure of chromosomes so that they work properly.
To be more precise, a total of 3491 evolutionary conserved DNA segments were found after a comparison of the human chromosome 21 and the mouse corresponding chromosomes. Of those 1229 corresponded to regions of known genes. Extensive computational, experimental, and evolutionary analysis of the remaining 2262 conserved DNA segments strongly supported the conclusion that these pieces of DNA are not genes.
The results of this study made clear that the understanding of the genome is more complicated than originally thought and that the non-gene regions are probably important for human disorders. Deleterious, pathologic mutations in the non-genic regions of the human genome may also cause or predispose to genetic disorders, including common diseases with strong genetic predisposition. These non-genic regions may also be important for the symptoms of trisomy 21 or Down syndrome.
The results of the study that was directed by Prof. S. Antonarakis and Dr E. Dermitzakis in the University of Geneva is/will be published in the prestigious Journal Nature on December 5, 2002.
The research in Prof Antonarakis laboratory was financed by the Swiss National Science foundation, the NCCR Frontiers in Genetics, and the "ChildCare" foundation.