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PMID: 18032726 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics.

Genome research ·Vol. 18 ·No. 1 ·2008-01-00 ·Pages 77-87

Roca X, Olson AJ, Rao AR, Enerly E, Kristensen VN, Børresen-Dale AL, Andresen BS, Krainer AR, Sachidanandam R

Abstract

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.

MeSH Terms
Animals Databases, Nucleic Acid Genetic Diseases, Inborn/genetics Genome, Human/genetics Humans Mice Polymorphism, Single Nucleotide RNA Splice Sites/genetics RNA Splicing/genetics
Chemicals
RNA Splice Sites
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Roca Xavier
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Olson Andrew J
Rao Atmakuri R
Enerly Espen
Kristensen Vessela N
Børresen-Dale Anne-Lise
Andresen Brage S
Krainer Adrian R
Sachidanandam Ravi
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.6859308
Published
2008-01-00
Epub
2007-00-21
Pages
77-87
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC2134769
Subset
IM
Grants
NCI NIH HHS · P01 CA013106 · United States
NCI NIH HHS · CA13106 · United States
External Links
PubMed source DOI: 10.1101/gr.6859308 PMC Full Text View journal details
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