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

Abstract:

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 non-canonical 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 Alzheimer's and breast cancer could be explained by changes in predicted splicing patterns. CONCLUSIONS:We have developed SpliceScan II, an effective and sensitive tool for predicting the detrimental effects of genomic variants on splicing leading to Mendelian and complex hereditary disorders. The method could potentially be used to screen resequenced patient DNA to identify de novo mutations and polymorphic variants that could contribute to a genetic disorder.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Churbanov A,Vorechovský I,Hicks C

doi

10.1186/1471-2105-11-22

subject

Has Abstract

pub_date

2010-01-12 00:00:00

pages

22

issn

1471-2105

pii

1471-2105-11-22

journal_volume

11

pub_type

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