Trisomy 21 is the most common aneuploidy in humans with a frequency of 1 in 700 live births and is by far the most common defined cause of mental retardation. To analyse which of the chromosome 21 genes is overexpressed early in development-giving rise to the Down syndrome phenotype-and to provide candidate genes for other HSA21 disease loci, we need a transcription map of the chromosome. Therefore, to enrich the gene map of human chromosome 21 we have undertaken a systematic approach to fine mapping and characterising expressed sequences generated by the various cDNA sequencing projects. In this report we show the localisation of the CAF1P60 gene to human chromosome 21 and its fine mapping to 21q22.2 between D21S333 and D21S334. This mapping position places CAF1P60 in a region of HSA21 which is strongly associated with the major features of Down syndrome. The function of this gene product may have important implications for the phenotype that arises from trisomy 21.