Genomics and medicine: an anticipation. From Boolean Mendelian genetics tomultifactorial molecular medicine

The major impact of the completion of the human genome sequence will be the understanding of diseases, with deduced therapy. In the field of genetic d isorders, we will complete the catalogue of monogenic diseases, also called Mendelian diseases because they obey the Boolean logic of Mendel's laws. T he major challenge now is to decipher the polygenic and multifactorial etio logy of common diseases, such as cancer, cardio-vascular, nutritional, alle rgic, auto-immune and degenerative diseases. In fact every gene, when mutat ed, is a potential disease gene, and we end up with the new concept of 'rev erse medicine'; i.e., deriving new diseases or pathogenic pathways from the knowledge of the structure and function of every gene. By going from seque nce to function (functional genomics and proteomics) we will gain insight i nto basic mechanisms of major functions such as cell proliferation, differe ntiation and development, which are perturbed in many pathological processe s. By learning the meaning of some non-coding and of regulatory sequences o ur understanding will gain in complexity generating a molecular and supramo lecular integrated physiology, helping to build a molecular patho-physiolog y of the different syndromes. Besides those cognitive advances, there are a lso other issues at stake, such as: progress in diagnostic and prediction ( predictive medicine); progress in therapy (pharmacogenomics and gene-based therapy); ethical issues; impact on business. (C) 2000 Academie des science s/Editions scientifiques et medicales Elsevier SAS.