CLONING THE CDNA OF HUMAN PWP2 WHICH ENCODES A PROTEIN WITH WD REPEATS AND MAPS TO 21Q22.3

We have used exon trapping to contribute to the development of the tra nscription map of chromosome 21q22.3 and to clone the genes responsibl e for disorders that map in the 21q22.3 region. Polypeptides deduced f rom three trapped sequences that map near PFKL showed homology to the yeast PWP2 gene. The full-length coding region of a human homologue of this yeast gene was subsequently cloned from human infant brain and f etal kidney cDNA libraries. The 919-codon open reading frame of human PWP2 belongs to the family of genes that contain tryptophan-aspartate (WD) repeats; other than its yeast counterpart, PWP2 is most closely h omologous to the beta subunits of the trimeric G-protein family and ma y putatively be involved in signal transduction. Northern blot analysi s revealed that the PWP2 gene is expressed in all fetal and adult huma n tissues examined (3.4 kb mRNA species). This single-copy gene maps a pproximately 200 kb proximal to PFKL in chromosome 21q22.3 between mar kers EHOC-1 and D21S25. (C) 1996 Academic Press, Inc.