Transcription of Alu DNA elements in blood cells of sporadic Creutzfeldt-Jakob disease (sCJD).
Alu DNA elements were long considered to be of no biological significance and thus have been only poorly defined. However, in the past Alu DNA elements with well-defined nucleotide sequences have been suspected to contribute to disease, but the role of Alu DNA element transcripts has rarely been investigated. For the first time, we determined in a real-time approach Alu DNA element transcription in buffy coat cells isolated from the blood of humans suffering from sporadic Creutzfeldt-Jakob disease (sCJD) and other neurodegenerative disorders. The reverse transcribed Alu transcripts were amplified and their cDNA sequences were aligned to genomic regions best fitted to database genomic Alu DNA element sequences deposited in the UCSC and NCBI data bases. Our cloned Alu RNA/cDNA sequences were widely distributed in the human genome and preferably belonged to the "young" Alu Y family. We also observed that some RNA/cDNA clones could be aligned to several chromosomes because of the same degree of identity and score to resident genomic Alu DNA elements. These elements, called paralogues, have purportedly been recently generated by retrotransposition. Along with cases of sCJD we also included cases of dementia and Alzheimer disease (AD). Each group revealed a divergent pattern of transcribed Alu elements. Chromosome 2 was the most preferred site in sCJD cases, besides chromosome 17; in AD cases chromosome 11 was overrepresented whereas chromosomes 2, 3 and 17 were preferred active Alu loci in controls. Chromosomes 2, 12 and 17 gave rise to Alu transcripts in dementia cases. The detection of putative Alu paralogues widely differed depending on the disease. A detailed data search revealed that some cloned Alu transcripts originated from RNA polymerase III transcription since the genomic sites of their Alu elements were found between genes. Other Alu DNA elements could be located close to or within coding regions of genes. In general, our observations suggest that identification and genomic localization of active Alu DNA elements could be further developed as a surrogate marker for differential gene expression in disease. A sufficient number of cases are necessary for statistical significance before Alu DNA elements can be considered useful to differentiate neurodegenerative diseases from controls.
Kiesel
Petra
P
German Primate Center, Göttingen, Germany.
Gibson
Toby J
TJ
Ciesielczyk
Barbara
B
Bodemer
Monika
M
Kaup
Franz-Josef
FJ
Bodemer
Walter
W
Zischler
Hans
H
Zerr
Inga
I
D020087:Alu Elements; D001483:Base Sequence; D058621:Blood Buffy Coat / Q000473:pathology / Q000502:physiology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood* / Q000235:genetics*; D018076:DNA, Complementary / Q000097:blood / Q000235:genetics; D005786:Gene Expression Regulation; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D012313:RNA / Q000097:blood / Q000235:genetics; D048348:Reverse Transcription; D016415:Sequence Alignment
D018076:DNA, Complementary; D012313:RNA