A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements

Background: Polymorphic variants and mutations disrupting canonical splicing isoforms are among the leading causes of human hereditary disorders. While there is a substantial evidence of aberrant splicing causing Mendelian diseases, the implication of such events in multi-genic disorders is yet to be well understood. We have developed a new tool (SpliceScan II) for predicting the effects of genetic variants on splicing and cis-regulatory elements. The novel Bayesian non-canonical 5'GC splice site (SS) sensor used in our tool allows inference on noncanonical exons. Results: Our tool performed favorably when compared with the existing methods in the context of genes linked to the Autism Spectrum Disorder (ASD). SpliceScan II was able to predict more aberrant splicing isoforms triggered by the mutations, as documented in DBASS5 and DBASS3 aberrant splicing databases, than other existing methods. Detrimental effects behind some of the polymorphic variations previously associated with...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Alexander G. Churbanov, Igor Vorechovsky, Chindo Hicks
• Keywords: Aberrant Splicing, BMCBI 2010, Canonical Splicing Isoforms, SpliceScan II