Diagnostics of pathogenic splicing mutations: does bioinformatics cover all bases?
Pathogenic splicing alterations caused by point mutations in both splice sites and auxiliary cis-regulatory elements are increasingly recognized as an important mechanism through which gene mutations cause human disease. Unfortunately, in routine genetic diagnostic settings, splicing mutations may escape identification, due to the lack of RNA samples. Since most patients are genotyped only, any computational prediction of mutation effects on splicing can be beneficial for the human geneticist. Here, we review common techniques to identify human point mutations and delineate the molecular basis for splice site recognition. Moreover, this article provides basic insights into web-tools predicting splice sites and cis-regulatory elements and discusses their benefits for judgment of clinically identified sequence variants of disease-specific genes.
Hartmann
Linda
L
Heinrich-Heine-University Duesseldorf, Institute for Virology, D-40225 Duesseldorf, Germany.
Theiss
Stephan
S
Niederacher
Dieter
D
Schaal
Heiner
H
D000465:Algorithms; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000175:diagnosis*; D014644:Genetic Variation; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics
D018076:DNA, Complementary; D012333:RNA, Messenger