From PREDs and open reading frames to cDNA isolation: Revisiting the humanchromosome 21 transcription map

A supernumerary copy of human chromosome 21 (HC21) causes Down syndrome. To understand the molecular pathogenesis of Down syndrome, it is necessary to identify all HC21 genes. The first annotation of the sequence of 21q confi rmed 127 genes, and predicted an additional 98 previously unknown "anonymou s" genes (predictions (PREDs) and open reading frames (C21orfs)), which wer e foreseen by exon prediction programs and/or spliced expressed sequence ta gs. These putative gene models still need to be confirmed as bona fide tran scripts. Here we report the characterization and expression pattern of the putative transcripts C21orf7, C21orf11, C21orf15, C21orf18, C21orf19, C21or f22, C21orf42, C21orf50, C21orf51, C21orf57, and C21orf58, the GC-rich sequ ence DNA-binding factor candidate GCFC (also known as C21orf66), PRED12, PR ED31, PRED34, PRED44, PRED54, and PRED56. Our analysis showed that most of the C21orfs originally defined by matching spliced expressed sequence tags were correctly predicted, whereas many of the PREDs, defined solely by comp uter prediction, do not correspond to genuine genes. Four of the six PREDs were incorrectly predicted: PRED44 and C21orf11 are portions of the same tr anscript, PRED31 is a pseudogene, and PRED54 and PRED56 were wrongly predic ted. In contrast, PRED12 (now called C21orf68) and PRED34 (C21orf63) are no w confirmed transcripts. We identified three new genes, C21orf67, C21orf69, and C21orf70, not previously predicted by any programs. This revision of t he HC21 transcriptome has consequences for the entire genome regarding the quality of previous annotations and the total number of transcripts. It als o provides new candidates for genes involved in Down syndrome and other gen etic disorders that map to HC21.