[Splice site mutations and atherosclerosis: mechanisms and prediction models].
Nucleotide variants in genes of the lipid metabolism influence the risk of premature atherosclerosis. Ten percent of all single nucleotide substitutions in these genes involve splice sites. The effects of these changes on mRNA splicing and phenotypic severity, however, are not inherently obvious from the nucleotide sequence. This review presents various genes of lipid metabolism with splicing mutations known to influence the risk of premature atherosclerosis. Mechanisms of pre-mRNA splicing are illustrated and different models for prediction of the effect of nucleotide substitutions on splice-site function are presented. The role of information theory-based models is emphasized along with its role for prediction of splice-site function and phenotypic severity of atherosclerosis.
von Kodolitsch
Y
Y
Universitätskrankenhaus Eppendorf Innere Medizin II Abteilung für Kardiologie Martinistrasse 52 D-20246 Hamburg. kodolitsch@uke.uni-hamburg.de
Nienaber
C A
CA
Fliegner
M
M
Rogan
P K
PK
D000367:Age Factors; D017398:Alternative Splicing; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics*; D006938:Hyperlipoproteinemia Type II / Q000235:genetics; D007257:Information Theory; D008055:Lipids / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D012313:RNA / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors; D014158:Transcription, Genetic
D008055:Lipids; D012322:RNA Precursors; D012333:RNA, Messenger; D012313:RNA