LOCALIZATION OF TDPX1, A HUMAN HOMOLOG OF THE YEAST THIOREDOXIN-DEPENDENT PEROXIDE REDUCTASE GENE (TPX), TO CHROMOSOME 13Q12

Reactive oxygen species and free radicals that are produced during nor mal metabolism can potentially damage cellular macromolecules. Defense s against such damage include a number of antioxidant enzymes that spe cifically target the removal or dismutation of the reactive agent. We report here the isolation and regional mapping of a human gene, TDPX1, that encodes an enzyme homologous to a yeast thioredoxin-dependent pe roxide reductase (thioredoxin peroxidase, TPX). The human TDPX1 coding sequence was determined from the product of a polymerase chain reacti on (PCR) amplification of human cDNA. Eased on PCR analysis of DNA fro m a human/rodent somatic cell hybrid panel, the TDPX1 locus was assign ed to chromosome 13. Further localization of the locus to 13q12 was ac complished by fluorescence in situ hybridization analysis, using as a probe DNA from a yeast artificial chromosome (YAC) that contains the T DPX1 gene. It was also determined by PCR analysis of various YACs that the TDPX1 locus is in the region of the dinucleotide repeat markers D 13S289 and D13S290. This regional mapping localizes the TDPX1 gene to a genomic region recently shown to contain the breast cancer susceptib ility gene BRCA2 and a gene associated with a form of muscular dystrop hy. Oxygen radical metabolism has been hypothesized to be important fo r cancer, muscular dystrophy, and other disorders, so TDPX1 should be considered a candidate gene for these diseases. (C) 1995 Academic Pres s, Inc.