title: A class of human exons with predicted distant branch points revealed by analysis of AG dinucleotide exclusion zones.
abstract: BACKGROUND
  The three consensus elements at the 3' end of human introns--the branch point sequence, the polypyrimidine tract, and the 3' splice site AG dinucleotide--are usually closely spaced within the final 40 nucleotides of the intron. However, the branch point sequence and polypyrimidine tract of a few known alternatively spliced exons lie up to 400 nucleotides upstream of the 3' splice site. The extended regions between the distant branch points (dBPs) and their 3' splice site are marked by the absence of other AG dinucleotides. In many cases alternative splicing regulatory elements are located within this region.
  
  
  RESULTS
  We have applied a simple algorithm, based on AG dinucleotide exclusion zones (AGEZ), to a large data set of verified human exons. We found a substantial number of exons with large AGEZs, which represent candidate dBP exons. We verified the importance of the predicted dBPs for splicing of some of these exons. This group of exons exhibits a higher than average prevalence of observed alternative splicing, and many of the exons are in genes with some human disease association.
  
  
  CONCLUSIONS
  The group of identified probable dBP exons are interesting first because they are likely to be alternatively spliced. Second, they are expected to be vulnerable to mutations within the entire extended AGEZ. Disruption of splicing of such exons, for example by mutations that lead to insertion of a new AG dinucleotide between the dBP and 3' splice site, could be readily understood even though the causative mutation might be remote from the conventional locations of splice site sequences.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Gooding
authors.forename: Francis
authors.initials: F
authors.lastname: Clark
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wollerton
authors.forename: Sushma-Nagaraja
authors.initials: SN
authors.lastname: Grellscheid
authors.forename: Harriet
authors.initials: H
authors.lastname: Groom
authors.forename: Christopher W J
authors.initials: CW
authors.lastname: Smith
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D005091:Exons / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009711:Nucleotides / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D009711:Nucleotides; D022821:RNA Splice Sites