HUMAN 25-HYDROXYVITAMIN-D 24-HYDROXYLASE CYTOCHROME-P450 SUBUNIT MAPSTO A DIFFERENT CHROMOSOMAL LOCATION THAN THAT OF PSEUDOVITAMIN D-DEFICIENT RICKETS

We have cloned part of the human 25-OHD 24-hydroxylase cytochrome P450 (P450cc24) cDNA. The characterized sequence consists of 776 bp of the coding and 720 bp of the 3'-untranslated region interrupted by an int ron. In the coding region we found 79.8% similarity in DNA and 87.5% i n deduced amino acid sequences between human and rat, with no similari ty in the 3'-untranslated region. By Southern blot hybridization of DN A from human-hamster somatic cell hybrids and by in situ immunofluores cence hybridization, we mapped P450cc24 to human chromosome 20q13.1. T his location of P450cc24 is different from that of pseudovitamin D-def icient rickets (PDDR), previously assigned to chromosome 12q14 by link age analysis, thus excluding it as a target of the PDDR mutation. Sinc e it is likely that PDDR is caused by a mutation in the 25-OHD 1alpha- hydroxylase P450 subunit (P450cc1alpha) our results do not support the hypothesis that the two cytochromes are encoded by a single gene.