Rogan PK, Mucaki EJ. Comment on PMID 23169495: Analysis of the effects of rare variants on splicing identifies alterations in GABAA receptor genes in autism spectrum disorder individuals. In: PubMed Commons [Internet]. Bethesda (MD): National Library of Medicine; 2012 Nov 21 [cited 2017 Dec 12].
Regarding GABRQ:c.306G>C: Whereas none of the splicing analysis programs tested predict outcomes shown in the mini-gene construct shown in Figure 2A, information theory-based exon definition analyses using ASSEDA (Mucaki EJ, 2013) was completely concordant. A novel band 116nt longer than the product expected from the wild type exon is observed. The mutation reduces the strength of the natural donor splice site of exon 3 from 9.5 -> 4.5 bits (32 fold). The pre-existing intronic cryptic site 116 nt downstream (8.6 bits) is 17 fold stronger than the mutated splice site. ASSEDA indicates that the total exon information (Ri,total) of wildtype exon is reduced (19.8 -> 14.8 bits) and the corresponding strength of the gap-surprisal adjusted cryptic exon significantly exceeds this (17.7 bits). The wildtype exon is predicted to be ~5-6 fold more abundant than the cryptic exon BEFORE mutation, and the cryptic exon is predicted to be ~8 fold more abundant AFTER mutation.