title: 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.
authors.affiliation: New Mexico State University, Biology Dept., MSC 3AF, PO Box 30001, Las Cruces, NM 88003, USA. atchourb@nmsu.edu
authors.forename: Alexander
authors.initials: A
authors.lastname: Churbanov
authors.forename: Igor
authors.initials: I
authors.lastname: Vorechovský
authors.forename: Chindo
authors.initials: C
authors.lastname: Hicks
mesh_terms: D001943:Breast Neoplasms; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*
chemical_list: D020033:Protein Isoforms