RT Journal
A1 Roca, Xavier
A1 Olson, Andrew J.
A1 Rao, Atmakuri R.
A1 Enerly, Espen
A1 Kristensen, Vessela N.
A1 Børresen-Dale, Anne-Lise
A1 Andresen, Brage S.
A1 Krainer, Adrian R.
A1 Sachidanandam, Ravi
T1 Features of 5′-splice-site efficiency derived from disease-causing mutations and comparative genomics
JF Genome Research 
JO Genome Research 
YR 2008 
FD January 01 
VO 18 
IS 1 
SP 77 
OP 87 
DO 10.1101/gr.6859308 
UL http://genome.cshlp.org/content/18/1/77.abstract 
AB Many human diseases, including Fanconi anemia, hemophilia B, neurofibromatosis, and phenylketonuria, can be caused by 5′-splice-site (5′ss) mutations that are not predicted to disrupt splicing, according to position weight matrices. By using comparative genomics, we identify pairwise dependencies between 5′ss nucleotides as a conserved feature of the entire set of 5′ss. These dependencies are also conserved in human–mouse pairs of orthologous 5′ss. Many disease-associated 5′ss mutations disrupt these dependencies, as can some human SNPs that appear to alter splicing. The consistency of the evidence signifies the relevance of this approach and suggests that 5′ss SNPs play a role in complex diseases.