Illegitimate transcription: its use in the study of inherited disease.

In 1988, by using the powerful and accurate cDNA/PCR technique, it was demonstrated that there are very low levels of dystrophin mRNA in a variety of non-muscle tissues, including cultured fibroblasts and lymphoblastoid cell lines. The phenomenon was also shown for a number of other tissue-specific genes, including beta-globin, factors VIIIc and IX, anti-Müllerian hormone, L-pyruvate kinase, retinal blue pigment, phenylalanine hydroxylase. The level of transcript in inappropriate cells is exceedingly low, perhaps one mRNA per 100-1000 cells. This low-level ubiquitous transcription of tissue-specific genes was called "illegitimate" or "ectopic" transcription, and has been proven to occur for 17 gene transcripts to date. The mechanism and biological significance of illegitimate transcription are still obscure, but, since illegitimate transcripts exhibit the same pathology as legitimate transcripts, they have been useful tool in the study of already 9 inherited diseases. This strategy will be applied widely for diseases where samples from the appropriate tissue for study is difficult to obtain, or where an mRNA is easier or more informative to study than a genomic DNA (as for large genes, or where alternative splicing is involved).