A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements
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 non-canonical exons.
Result: 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
22-[25pp]
Churbanov, Alexander
3ef4f6a4-211f-418c-9c4f-7b88de55da12
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Hicks, Chindo
5be4f446-3bfd-4992-9c01-738e19bcd466
12 January 2010
Churbanov, Alexander
3ef4f6a4-211f-418c-9c4f-7b88de55da12
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Hicks, Chindo
5be4f446-3bfd-4992-9c01-738e19bcd466
Churbanov, Alexander, Vorechovsky, Igor and Hicks, Chindo
(2010)
A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements.
BMC Bioinformatics, 11 (1), .
(doi:10.1186/1471-2105-11-22).
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.
Result: 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
Text
1471-2105-11-22.pdf
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Available under License Other.
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Published date: 12 January 2010
Identifiers
Local EPrints ID: 72043
URI: http://eprints.soton.ac.uk/id/eprint/72043
ISSN: 1471-2105
PURE UUID: b838591a-422b-4fa1-9331-ed95dbd9f61b
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Date deposited: 18 Jan 2010
Last modified: 14 Mar 2024 02:48
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Author:
Alexander Churbanov
Author:
Chindo Hicks
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