OMIA:001794-9940 : Cystic fibrosis in Ovis aries (sheep) |
In other species: domestic ferret , pig
Categories: Digestive / alimentary phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 219700 (trait) , 602421 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2017
Species-specific description: Fan et al. (2018) "describe the generation of a sheep model for CF using CRISPR/Cas9 genome editing and somatic cell nuclear transfer (SCNT) techniques" and propose "the generation of specific human CF disease–associated mutations in sheep [to] ...advance personalized medicine for this common genetic disorder."
The same research team later developed models for the most common CSFR mutations found in human patients in the USA: "we describe the generation of CFTR^F508del/F508del and CFTR^G542X/G542X lambs using CRISPR/Cas9 and somatic cell nuclear transfer (SCNT)." (Perisse et al., 2021)
(Genetically-modifed organisms; GMO)
(Entry was edited by Hannah Edgell 24/08/2022)
Molecular basis: Fan et al. (2028) " generated cells with CFTR gene disruption [in exon 2 and exon 11] and used them for production of CFTR–/– and CFTR+/– lambs. The newborn CFTR–/– sheep developed severe disease consistent with CF pathology in humans."
Perisse et al. (2021) "introduced either F508del or G542X mutations into sheep fetal fibroblasts that were subsequently used as nuclear donors for SCNT. The newborn CF lambs develop pathology similar to CFTR -/- sheep and CF patients. Moreover, tracheal epithelial cells from the CFTRF508del / F508del lambs responded to a human CFTR (hCFTR) potentiator and correctors, and those from CFTRG542X / G542X lambs showed modest restoration of CFTR function following inhibition of nonsense-mediated decay (NMD) and aminoglycoside antibiotic treatments."
Breed:
Romney (Sheep) (VBO_0001581).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| CFTR | cystic fibrosis transmembrane conductance regulator | Ovis aries | 4 | NC_056057.1 (52438143..52249612) | CFTR | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Inferred EVA rsID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1479 | Romney (Sheep) | Cystic fibrosis | CFTR | nonsense (stop-gain) | Genome-editing (CRISPR-Cas9) | Oar_rambouillet_v1.0 | 4 | g.57192317C>A | c.1621G>T | p.(G541*) | NM_001009781.1; NP_001009781.1; published as p.(G542X), coordinates in this table are updated to recent reference sequence | 2021 | 34632318 | ||||
| 1478 | Romney (Sheep) | Cystic fibrosis | CFTR | deletion, small (<=20) | Genome-editing (CRISPR-Cas9) | Oar_rambouillet_v1.0 | 4 | g.57218683_57218685del | c.1518_1520del | p.(F507del) | NM_001009781.1; NP_001009781.1; published as p.(F508del), coordinates are updated in this table to recent reference sequence | 2021 | 34632318 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001794-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2023 | Kerschner, J.L., Paranjapye, A., Schacht, M., Meckler, F., Huang, F., Bebek, G., Van Wettere, A.J., Regouski, M., Perisse, I.V., White, K.L., Polejaeva, I.A., Leir, S.H., Harris, A. : |
| Transcriptomic analysis of lung development in wildtype and CFTR-/- sheep suggests an early inflammatory signature in the CF distal lung. Funct Integr Genomics 23:135, 2023. Pubmed reference: 37085733 . DOI: 10.1007/s10142-023-01050-y. | |
| 2021 | Périssé, I.V., Fan, Z., Van Wettere, A., Liu, Y., Leir, S.H., Keim, J., Regouski, M., Wilson, M.D., Cholewa, K.M., Mansbach, S.N., Kelley, T.J., Wang, Z., Harris, A., White, K.L., Polejaeva, I.A. : |
| Sheep models of F508del and G542X cystic fibrosis mutations show cellular responses to human therapeutics. FASEB Bioadv 3:841-854, 2021. Pubmed reference: 34632318 . DOI: 10.1096/fba.2021-00043. | |
| 2020 | Menchaca, A., Dos Santos-Neto, P.C., Mulet, A.P., Crispo, M. : |
| CRISPR in livestock: From editing to printing. Theriogenology 150:247-254, 2020. Pubmed reference: 32088034 . DOI: 10.1016/j.theriogenology.2020.01.063. | |
| 2018 | Fan, Z., Perisse, I.V., Cotton, C.U., Regouski, M., Meng, Q., Domb, C., Van Wettere, A.J., Wang, Z., Harris, A., White, K.L., Polejaeva, I.A. : |
| A sheep model of cystic fibrosis generated by CRISPR/Cas9 disruption of the CFTR gene. JCI Insight 3:, 2018. Pubmed reference: 30282831 . DOI: 10.1172/jci.insight.123529. |
Edit History
- Created by Imke Tammen2 on 19 Apr 2021
- Changed by Imke Tammen2 on 24 Aug 2022