Molecular genetic characterization and comparative mapping of the human PCP4 gene.

The mouse Pcp4 gene is highly expressed in brain, primarily in cerebellar Purkinje cells. It maps to chromosome 16 (Chr 16), in a region of conserved synteny with human chromosome 21 (Chr 21). To further characterize PCP4 and its possible contribution to cerebellar hypoplasia in trisomy 21, or Down Syndrome (DS), we cloned and sequenced the full length human cDNA, isolated a YAC which carries the entire gene, determined the gene structure, and characterized its expression. The gene spans at least 55 kb and contains two introns, the placement of which is the same in mouse. Expression in the mouse brain during development was detected at embryonic day 10, and thereafter through development. The PCP4 YAC was placed on the human Chr 21 YAC contig by a link to a YAC carrying the markers D21S15 and D21S349. This placement distal to ETS2 was confirmed by mapping on a somatic cell hybrid panel of Chr 21 translocations. This position caused an apparent break in gene order with mouse Chr 16. However, mapping in the mouse was reassessed, and Pcp4 and a linked marker, D16Mit71, were both moved distal to Ets2, corresponding to the position of PCP4 on Chr 21.