Rogan P K, Faux B M, Schneider T D
Department of Human Genetics, Allegheny University of the Health Sciences, Pittsburgh, PA 15212, USA.
Hum Mutat. 1998;12(3):153-71. doi: 10.1002/(SICI)1098-1004(1998)12:3<153::AID-HUMU3>3.0.CO;2-I.
Splice site nucleotide substitutions can be analyzed by comparing the individual information contents (Ri, bits) of the normal and variant splice junction sequences [Rogan and Schneider, 1995]. In the present study, we related splicing abnormalities to changes in Ri values of 111 previously reported splice site substitutions in 41 different genes. Mutant donor and acceptor sites have significantly less information than their normal counterparts. With one possible exception, primary mutant sites with <2.4 bits were not spliced. Sites with Ri values > or = 2.4 bits but less than the corresponding natural site usually decreased, but did not abolish splicing. Substitutions that produced small changes in Ri probably do not impair splicing and are often polymorphisms. The Ri values of activated cryptic sites were generally comparable to or greater than those of the corresponding natural splice sites. Information analysis revealed preexisting cryptic splice junctions that are used instead of the mutated natural site. Other cryptic sites were created or strengthened by sequence changes that simultaneously altered the natural site. Comparison between normal and mutant splice site Ri values distinguishes substitutions that impair splicing from those which do not, distinguishes null alleles from those that are partially functional, and detects activated cryptic splice sites.
剪接位点核苷酸替换可通过比较正常和变异剪接连接序列的个体信息含量（Ri，比特）来分析[罗根和施奈德，1995年]。在本研究中，我们将剪接异常与41个不同基因中111个先前报道的剪接位点替换的Ri值变化相关联。突变的供体位点和受体位点的信息明显少于其正常对应位点。除了一种可能的例外情况，信息含量小于2.4比特的初级突变位点不发生剪接。Ri值大于或等于2.4比特但小于相应天然位点的位点通常剪接减少，但并未消除剪接。导致Ri值微小变化的替换可能不会损害剪接，且往往是多态性。激活的隐蔽位点的Ri值通常与相应天然剪接位点的Ri值相当或更高。信息分析揭示了被用于替代突变天然位点的预先存在的隐蔽剪接连接。其他隐蔽位点通过同时改变天然位点的序列变化而产生或增强。正常和突变剪接位点Ri值之间的比较可区分损害剪接的替换与不损害剪接的替换，区分无效等位基因与部分功能的等位基因，并检测激活的隐蔽剪接位点。
