Complete genomic sequence and analysis of the prion protein gene region from three mammalian species.
The prion protein (PrP), first identified in scrapie-infected rodents, is encoded by a single exon of a single-copy chromosomal gene. In addition to the protein-coding exon, PrP genes in mammals contain one or two 5'-noncoding exons. To learn more about the genomic organization of regions surrounding the PrP exons, we sequenced 10(5) bp of DNA from clones containing human, sheep, and mouse PrP genes isolated in cosmids or lambda phage. Our findings are as follows: (1) Although the human PrP transcript does not include the untranslated exon 2 found in its mouse and sheep counterparts, the large intron of the human PrP gene contains an exon 2-like sequence flanked by consensus splice acceptor and donor sites. (2) The mouse Prnpa but not the Prnpb allele found in 44 inbred lines contains a 6593 nucleotide retroviral genome inserted into the anticoding strand of intron 2. This intracisternal A-particle element is flanked by duplications of an AAGGCT nucleotide motif. (3) We found that the PrP gene regions contain from 40% to 57% genome-wide repetitive elements that independently increased the size of the locus in all three species by numerous mutations. The unusually long sheep PrP 3'-untranslated region contains a "fossil" 1.2-kb mariner transposable element. (4) We identified sequences in noncoding DNA that are conserved between the three species and may represent biologically functional sites.
Lee
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Department of Molecular Biotechnology, University of Washington, Seattle, Washington 98195-7730 USA.
Westaway
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Smit
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Wang
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Seto
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Chen
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Acharya
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Ankener
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Baskin
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Cooper
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Yao
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Prusiner
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Hood
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LE
D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000379:methods*; D012756:Sheep; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics
D011328:Prions; D015678:Viral Structural Proteins