Contemporary work is often complex because it is dynamic [47], and managers frame rules and procedures for workers in an effort to tame this complexity [48].
Taking into account the splice frame rules, we put forward here an original two-step model to account for the inclusion of H2d in vertebrate COE proteins (Fig. 4).
Taking into account the splice frame rules, we put forward here an original two-step duplication model to account for H2d inclusion in vertebrate COE proteins The vertebrate gene configuration is such that it remains possible to remove H2d through alternative splicing, through exon-skipping.
Comeback is too strong a word, but mainframes no longer look that outdated.Until the 1980s mainframes, so called because the processing unit was originally housed in a huge metal frame, ruled supreme in corporate data centres.
This reading frame rule holds true for ~91% of DMD cases [ 2] and has inspired the development of the exon skipping strategy, which employs antisense oligonucleotides (AONs).
One BMD patient had an out-of-frame duplication of exons 3 6 as an exception to the reading frame rule, one DMD patient showed an isolated duplication of exon 2, and one BMD patient had a deletion of exon 14.
BMD typically results from shortened, but in-frame, transcripts of the DMD gene that allow for expression of limited amounts of an internally truncated, but partially functional, protein (the reading frame rule) [ 31].
7, 8 More importantly, the reading frame rule offered two potential avenues for therapy: 1) Insert the dystrophin-coding sequence from mildly affected/asymptomatic BMD patients into viral vectors and exploit these smaller payloads.
An extension to the exon shuffling theory is the splice frame rule, which states that the phases of introns bordering domains tend to match following a successful shuffling event [ 27].
However, this exon was probably not symmetrical (see Fig. 2B) and, due the splice frame rule, only the ancestral or the duplicated exon could be incorporated in the coding transcript without disrupting the open reading frame, a classical case of mandatory alternative splicing [ 48, 49].
The reading frame rule holds true in the majority of dystrophin mutations, 6 with any discordance between the genotype and phenotype normally resolved by studying the dystrophin mRNA and identifying secondary effects on RNA processing as a consequence of the mutation.
