Baralle D, Baralle M
Department of Medical Genetics, Box 134, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
J Med Genet. 2005 Oct;42(10):737-48. doi: 10.1136/jmg.2004.029538.
Variations in new splicing regulatory elements are difficult to identify exclusively by sequence inspection and may result in deleterious effects on precursor (pre) mRNA splicing. These mutations can result in either complete skipping of the exon, retention of the intron, or the introduction of a new splice site within an exon or intron. Sometimes mutations that do not disrupt or create a splice site activate pre-existing pseudo splice sites, consistent with the proposal that introns contain splicing inhibitory sequences. These variants can also affect the fine balance of isoforms produced by alternatively spliced exons and in consequence cause disease. Available genomic pathology data reveal that we are still partly ignorant of the basic mechanisms that underlie the pre-mRNA splicing process. The fact that human pathology can provide pointers to new modulatory elements of splicing should be exploited.
新型剪接调控元件的变异很难仅通过序列检查来识别，并且可能对前体（pre）mRNA剪接产生有害影响。这些突变可能导致外显子完全跳跃、内含子保留，或者在外显子或内含子内引入新的剪接位点。有时，不破坏或创建剪接位点的突变会激活预先存在的假剪接位点，这与内含子包含剪接抑制序列的观点一致。这些变异还会影响可变剪接外显子产生的异构体的精细平衡，进而导致疾病。现有的基因组病理学数据表明，我们对前体mRNA剪接过程的基本机制仍部分未知。人类病理学能够为剪接的新调控元件提供线索这一事实应加以利用。
