Paradigm shift in gene-finding method: From bench-top approach to desk-top approach (review)

Gene-finding methods are classified into homology-based bench-top approach (degenerate cDNA-PCR and cDNA selection), ab initio bench-top approach (cDNA subtraction, two-hybrid system, and exon trapping), homology-based desk-top approach (BLAST search), ab initio desk-top approach (Fgenesh and GENSCAN programs), and hybrid desk-top approach (GenomeScan program). cDNA-library screening, cDNA-PCR, and RACE are used to isolate cDNAs for complete coding sequences. Because WNT signaling molecules are potent targets for oncology, regenerative medicine, and other fields of medical science, we have cloned and characterized many human genes encoding WNT signaling molecules, including 13 out of 19 human WNT genes, and 9 out of 10 human FZD genes. We used degenerate cDNA-PCR and cDNA-library screening in the 20th century, while we use BLAST program and cDNA-PCR in the 21st century. The interval between gene-finding and manuscript-publication in my laboratory was 17.2+/-7.5 (mean +/- SD) months in the 20th century (n=13), 11.5+/-7.8 months in 2001 (n=19), and 5.5+/-1.6 months in 2002 (n=13). The interval using desk-top gene-finding approach (7.2+/-2.6 months, n=30) was significantly shorter than that using bench-top approach (19.8+/-8.0 months, n=15) (p=0.003). Gene-finding has been significantly accelerated due to paradigm shift from bench-top approach to desk-top approach. Dramatic increase of information about human genome, transcriptome and proteome accompanied by improvements of genomics, proteonics and bioinformatics technologies will accelerate paradigm shift from bench-top science to desk-top science.