PERIPHERIN GENE IS LINKED TO KERATIN-18 GENE ON HUMAN-CHROMOSOME-12

Peripherin is a neuron on-spectfic intermediate filament (IF) protein, found primarily in phylogenetically old regions of the nervous system . Whereas other neuronal IF genes have only two to three introns and a re scattered in the genome, the peripherin gene (PRPH) has a complex i ntron-exon structure like nonneuronal IF genes that are clustered in t andem arrays, e.g., those encoding the keratins. We used a cosmid cont aining the human peripherin gene (PRPH) to determine its chromosomal l ocation in relationship to nonneuronal IF genes. Using a rodent-human mapping panel, we localized the PRPH gene to human chromosome 12. Sinc e a cluster of keratin genes maps to 12q12-13, polymorphic markers wer e developed for PRPH and for one of the keratin genes presumed to be i n the cluster keratin 18 (KRT18). Both markers were typed in CEPH refe rence families. Pairwise and multipoint analyses of the CEPH data reve aled that KRT18 is tightly linked to DNA markers D12S4, D12S22, D12S90 , D12S96 and D12S103, which lie between D12S18 and D12S8, with odds gr eater than 1000:1. These markers are physically located at 12q11-13, t hus supporting the fine localization of KRT18 in or near the group of type II keratins in this region. Furthermore, linkage analysis showed that the peripherin gene (PRPH) is tightly linked to KRT18 (($) over c ap Z = 15.73, ($) over cap theta = 0.013), and therefore appears to be in close proximity to the cluster.