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Review: Genotype-Phenotype Relationships in the Context of Transcriptional Adaptation and Genetic Robustness

Genotype-Phenotype Relationships in the Context of Transcriptional Adaptation and Genetic Robustness.
Jakutis G, Stainier DYR. Annu Rev Genet. 2021 Jul 27. doi: 10.1146/annurev-genet-071719-020342. Online ahead of print.
https://www.annualreviews.org/doi/pdf/10.1146/annurev-genet-071719-020342

Paper: Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotide

Mostly phosphorothioate work

Ham KA, Keegan NP, McIntosh CS, Aung-Htut MT, Zaw K, Greer K, Fletcher Sue, Wilton SD. Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides. Sci Rep. 2021;11(1):15137 doi:10.1038/s41598-021-94639-x
https://www.nature.com/articles/s41598-021-94639-x

Genetic compensation in soybean (no Morpholino)

Genetic compensation in soybean: I am putting this in the blog as an example of an organism distant from zebrafish which is also compensating for mutation.

Li X, Fang C, Yang Y, Lv T, Su T, Chen L, Nan H, Li S, Zhao X, Lu S, Dong L, Cheng Q, Tang Y, Xu M, Abe J, Hou X, Weller JL, Kong F, Liu B. Overcoming the genetic compensation response of soybean florigens to improve adaptation and yield at low latitudes. Curr Bio. 2021;[Epub] doi:10.1016/j.cub.2021.06.037
https://www.cell.com/current-biology/fulltext/S0960-9822(21)00832-0

Mutant-morphant mismatch but no genetic compensation

Zebrafish Chromosome 14 Gene Differential Expression in the fmr1 h u2787 Model of Fragile X Syndrome.
Barthelson K, Baer L, Dong Y, Hand M, Pujic Z, Newman M, Goodhill GJ, Richards RI, Pederson SM, Lardelli M. Front Genet. 2021 May 31;12:625466. doi: 10.3389/fgene.2021.625466. eCollection 2021.

https://www.frontiersin.org/articles/10.3389/fgene.2021.625466/full

A study of fmr1 in zebrafish assessed changes in related genes between mutants and wild-types, looking for evidence of genetic compensation. No such changes where found, though the mutant and morphant phenotypes were not in complete concordance.

Morphant vs mutant: "...this knockout line is deemed unsuitable for our study."

Here’s a nice description of why, in this study, morphants are preferable to mutants.

"To determine whether Par-3 is involved in polarizing the dynamics of Notch signaling endosomes, we disrupted the activity of the zebrafish orthologous gene pard3ab (theretofore referred to as par-3) via microinjection of a well-established antisense morpholino oligonucleotide (MO) (19, 20, 41). Despite the fact that a maternal zygotic germline pard3ab knockout has been previously generated, it has grossly normal brain morphology and survives largely to adulthood (42). This phenotype is distinct from defective brain morphology and abnormal proliferation/differentiation states observed in the morphants, suggesting that genetic compensation (43) is at play. Therefore, this knockout line is deemed unsuitable for our study."

Zhao X, Garcia JQ, Tong K, Chen X, Yang B, Li Q, Dai Z, Shi X, Seiple IB, Huang B, Guo S. Polarized endosome dynamics engage cytoplasmic Par-3 that recruits dynein during asymmetric cell division. Sci Adv. 2021;7(24):eabg1244. doi:10.1126/sciadv.abg1244

https://advances.sciencemag.org/content/7/24/eabg1244

Therapeutic Modulation of RNA Splicing in Malignant and Non-Malignant Disease (Review)

Therapeutic Modulation of RNA Splicing in Malignant and Non-Malignant Disease.
El Marabti E, Abdel-Wahab O. Trends Mol Med. 2021 May 13:S1471-4914(21)00100-3. doi: 10.1016/j.molmed.2021.04.005.
https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00100-3

SARS-CoV-2 RNA targets for steric blocking

Potantial targets for steric blocking on the SARS-CoV-2 genome and transcripts.

The SARS-CoV-2 RNA interactome.
Lee S, Lee YS, Choi Y, Son A, Park Y, Lee KM, Kim J, Kim JS, Kim VN. Mol Cell. 2021 Apr 27:S1097-2765(21)00327-0. doi: 10.1016/j.molcel.2021.04.022. Online ahead of print.

https://www.sciencedirect.com/science/article/pii/S1097276521003270

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