Genomic characterization of the human prion protein (PrP) gene locus |
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Authors: | Eleni Makrinou John Collinge Michael Antoniou |
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Institution: | (1) MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK, GB;(2) Nuclear Biology Group, Division of Medical and Molecular Genetics, GKT Medical School, King's College London, Guy's Campus, London SE1 9RT, UK, GB |
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Abstract: | Prion protein (PrP) is intimately linked with a class of neurodegenerative diseases known as transmissible spongiform encephalopathies
(TSEs). Employing bioinformatics and direct molecular analysis, we demonstrated that the human PrP gene (PRNP) locus, which
is situated at Chromosome (Chr) position 20p12-ter, contains three genes within a 55-kb interval: PRNP; DOPPEL or PRND, located
20 kb 3? of PRNP; and a novel gene, designated PRNT, that maps 3 kb 3? to PRND and is transcribed to generate at least three
alternatively spliced mRNAs. All three genes of this locus demonstrate low sequence homology, implying that, although they
may be evolutionarily related, they are functionally distinct. Analysis of both adult and fetal human tissues confirmed the
ubiquitous but variable expression profile of PRNP, with the highest levels observed in the CNS and testis. Contrastingly,
although PRND shows a wide tissue expression pattern in fetal tissues, it is expressed exclusively in adult testis, whereas
all three PRNT isoforms were detected only in adult testis, implying that PRND is developmentally regulated. An investigation
of the regulatory mechanisms underlying this complex gene expression pattern from the PRNP locus should provide insight into
the function of these genes and the possible involvement of the non-PrP proteins in the development of TSEs. |
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