Figure 1.

Examples of the potential effects of different sequence polymorphisms on two hypothetical loci, A and B. In this scenario, locus A has two annotated transcripts (RNA-1 and RNA-2, dark blue), expressed in different tissues. Sequence polymorphism 1 would affect an annotated exon of locus A that occurs in the annotated transcript RNA-1 and in unannotated transcripts (RNA-4 and RNA-5, cyan) and not in RNA-2. Variant 2 would affect a coding exon that is present in both the annotated coding transcripts and also in the non-coding transcript RNA-7. These are examples of polymorphisms that would currently be considered to be the only likely 'functional' polymorphisms in locus A, as they are the only ones to affect the annotated transcripts, RNA-1 and RNA-2. Polymorphisms 3-6 are 'non-coding' polymorphisms, with polymorphism 6 being relatively distant from locus A. However, in this example, these polymorphisms in fact overlap unannotated transcripts (cyan) within locus A, some of which extend outside locus A or encode regulatory small RNA molecules that act in trans on other loci. Polymorphism 3 overlaps a novel exon that is a part of unannotated transcripts RNA-4, RNA-5 and RNA-6. It could thus affect transcripts derived from both locus A and locus B, whether the two loci are nearby or distant in the genome. Polymorphism 4 overlaps a regulatory region for unannotated transcripts RNA-5 and RNA-6 and the 5' untranslated region of RNA-4. It could thus also affect expression of transcripts from both locus A and locus B. Polymorphism 5 overlaps a regulatory region for a non-coding RNA (transcript RNA-7) that is a precursor for a small RNA, a miRNA (RNA-8). Thus, this polymorphism and polymorphism 2, which also overlaps this non-coding RNA, could affect expression of other loci regulated by this small RNA in trans. Polymorphism 6 affects a more distant region in the genome that is connected to locus A by transcript RNA-9. All transcripts are shown transcribed from left to right; non-coding portions of transcripts are represented as thin boxes; coding portions are represented as thicker boxes; introns are shown as thin lines; asterisks indicated polymorphisms.