Functional genomics in nephrology.

has come true. As Hieter and Boguski [3] have said, Introduction ‘... it refers to the development and application of global (genome-wide or system-wide) experimental We are facing a new era in molecular biology. The approaches to assess gene function by making use of complete DNA sequences of the genomes of many the information and reagents provided by structural organisms have been analysed. The Human Genome genomics’. In mammals, the genome is thought to Project is scheduled to finish prior to 2003. Now it is encode about a hundred thousand genes. Analyses of announced that approximately 90% of the data will be the whole gene expression cannot be achieved by the made accessible to the public in the coming year. This methods that we had in the past. Recent DNA technomeans that cloning of genes or characterization of the logy, such as microarrays, DNA chips, or direct largegenomic structures will no longer be main issues in the scale sequencing of cDNA [5–8] allows the handling near future. Expanding DNA databases such as of 10–100 thousand genes simultaneously. Microarray, GenBank are accumulating more than 3 million one of the promising methods, could enable the sequence records. Most of the data has come from EST imaging of large-scale (over thousands) northern blot (expressed sequence tag) projects collecting sequences or dot-blot analyses. Thousands of cDNAs or synthetic directly from whole cDNA libraries that started in oligonucleotides are fixed on small membranes, silica 1990s [1,2]. More than 1.2 million entries for human wafers, or glass slides in high density, for hybridization ESTs and over four hundred thousand mouse ESTs are to either fluorescent or radiolabelled probes. The recorded in dbEST (release 021999), and 80% of human changes of gene activity can be detected by the intensity coding sequences are in databases. The data can provide of hybridization signals. new powerful tools; for example, application to A shortcoming of the microarray is the relatively RNA expression analysis, hunting for candidate disease large amount of RNA required, especially for preparing genes or characterization of tissue-specific genes. fluorescent probes [9]. Because special and expensive Combination with computer analyses and gene technohardware such as the robotic printing of a large number logy manipulating large-scale sequences will potentially of templates, scanning devices, and image processing allow the exploration of all genes and the deduced tools [10,11] is required to prepare microarrays, it has proteins in a systematic fashion based on the informabeen difficult for many researchers to apply this techtion of whole genome sequences [3,4]. nique in their own laboratories. It is becoming easier to access these techniques because several kinds of array are now available commercially [12]. When using mic‘Functional genomics’ to understand how roarray to compare the expression of genes between several conditions, a considerable numbers of genes differential genes work would show up as potential targets for analyses [13,14]. The dynamic alteration of the clustering genes in conThe results of genome projects, including Homo sapicert would provide clues to understanding the dynamics ens, will impact on basic research as well as clinical of cellular function that cannot be obtained by investipractice much more than hitherto. The genome is the gation of a single gene. It should be borne in mind that fundamental blueprint of the cell function. The commany of the sequences in microarray came from EST prehensive knowledge of the whole genome sequence clusters of which most of the functions were unknown, will make feasible the analyses of the expression of all leading researchers to perform the additional intensive genes in response to various physiological or patholoexperiments to characterize several target genes. gical conditions. A concept of ‘functional genomics’