Genomic structure of the human prion protein gene

Am J Hum Genet. 1991 Aug;49(2):320-9.


Creutzfeld-Jacob disease and Gerstmann-Sträussler syndrome are rare degenerative disorders of the nervous system which have been genetically linked to the prion protein (PrP) gene. The PrP gene encodes a host glycoprotein of unknown function and is located on the short arm of chromosome 20, a region with few known genes or anonymous markers. The complete structure of the PrP gene in man has not been determined despite considerable interest in its relationship to these unusual disorders. We have determined that the human PrP gene has the same simple genomic structure seen in the hamster gene and consists of two exons and a single intron. In contrast to the hamster PrP gene the human gene appears to have a single major transcriptional start site. The region immediately 5' of the transcriptional start site of the human PrP gene demonstrates the GC-rich features commonly seen in housekeeping genes. Curiously, the genomic clone we have isolated contains a 24-bp deletion that removes one of five octameric peptide repeats predicted to form a B-pleated sheet in this region of the PrP. We have also identified 5' of the PrP gene an RFLP which has a high degree of heterozygosity and which should serve as a useful marker for the pter-12 region of human chromosome 20.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Brain / microbiology
  • Chromosome Deletion
  • DNA / genetics
  • DNA / isolation & purification
  • Deoxyribonucleases, Type II Site-Specific
  • Gene Library
  • Genes, Viral
  • Humans
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Polymerase Chain Reaction / methods
  • Polymorphism, Restriction Fragment Length*
  • PrPSc Proteins
  • Prions / genetics
  • Restriction Mapping
  • Transcription, Genetic
  • Viral Proteins / genetics*
  • Viral Structural Proteins / genetics


  • Oligonucleotide Probes
  • PrPSc Proteins
  • Prions
  • Viral Proteins
  • Viral Structural Proteins
  • DNA
  • CAGCTG-specific type II deoxyribonucleases
  • Deoxyribonucleases, Type II Site-Specific