The human splicing code reveals new insights into the genetic determinants of disease

• DOI: 10.1126/science.1254806
• Publication Date: 2014-12-19T10:32:44Z
• Authors: Hui Y. Xiong; Babak Alipanahi; Leo J. Lee; Hannes Bretschneider; Daniele Merico; Ryan K. C. Yuen; Yimin Hua; Serge Gueroussov; Hamed S. Najafabadi; Timothy R. Hughes; Quaid Morris; Yoseph Barash; Adrian R. Krainer; Nebojsa Jojic; Stephen W. Scherer; Benjamin J. Blencowe; Brendan J. Frey
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

To facilitate precision medicine and whole-genome annotation, we developed a machine-learning technique that scores how strongly genetic variants affect RNA splicing, whose alteration contributes to many diseases. Analysis of more than 650,000 intronic exonic revealed widespread patterns mutation-driven aberrant splicing. Intronic disease mutations are 30 nucleotides from any splice site alter splicing nine times as often common variants, missense have the least impact on protein function five likely others We detected tens thousands disease-causing mutations, including those involved in cancers spinal muscular atrophy. Examination found using sequencing individuals with autism misspliced genes neurodevelopmental phenotypes. Our approach provides evidence for causal should enable new discoveries medicine.