Understanding human DNA variants affecting pre-mRNA splicing in the NGS era.

Understanding human DNA variants affecting pre-mRNA splicing in the NGS era. Adv Genet. 2019;103:39-90 Authors: Dufner-Almeida LG, do Carmo RT, Masotti C, Haddad LA Abstract Pre-mRNA splicing, an essential step in eukaryotic gene expression, relies on recognition of short sequences on the primary transcript intron ends and takes place along transcription by RNA polymerase II. Exonic and intronic auxiliary elements may modify the strength of exon definition and intron recognition. Splicing DNA variants (SV) have been associated with human genetic diseases at canonical intron sites, as well as exonic substitutions putatively classified as nonsense, missense or synonymous variants. Their effects on mRNA may be modulated by cryptic splice sites associated to the SV allele, comprehending exon skipping or shortening, and partial or complete intron retention. As splicing mRNA outputs result from combinatorial effects of both intrinsic and extrinsic factors, in vitro functional assays supported by computational analyses are recommended to assist SV pathogenicity assessment for human Mendelian inheritance diseases. The increasing use of next-generating sequencing (NGS) targeting full genomic gene sequence has raised awareness of the relevance of deep intronic SV in genetic diseases and inclusion of pseudo-exons into mRNA. Finally, we take advantage of recent advances in sequencing and computational technologies to analyze alternative splicing...
Source: Advances in Genetics - Category: Genetics & Stem Cells Authors: Tags: Adv Genet Source Type: research