Experimental annotation of the human genome using microarray technology

The most important product of the sequencing of a genome is a complete, acc urate catalogue of genes and their products, primarily messenger RNA transc ripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a g enome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonu cleotide synthesis, we devised an experimental approach to validate and ref ine computational gene predictions and define full-length transcripts on th e basis of co-regulated expression of their exons. These methods can provid e more accurate gene numbers and allow the detection of mRNA splice variant s and identification of the tissue- and disease-specific conditions under w hich genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two exp erimental conditions. We discuss implications for more comprehensive, consi stent and reliable genome annotation, more efficient, full-length complemen tary DNA cloning strategies and application to complex diseases.