OMIA:002176-9940 : Meckel-like hepatorenal fibrocystic dysplasia syndrome in Ovis aries (sheep) |
Categories: Renal / urinary system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 607361 (trait) , 609884 (gene) , 610688 (trait) , 613550 (trait) , 216360 (trait)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2017
Molecular basis: Stayner et al. (2017) reported two almost adjacent missense mutations (p.Ile681Asn and p.Ile687Ser) in complete linkage disequilibrium (and which can, therefore, be regarded as a single variant) within the TMEM67 gene as being likely causal of this disorder in two flocks (one Perendale and one Coopworth) located 500 kms apart and with no history of interbreeding within the last 40 years.
Genetic engineering:
Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Stayner et al. (2017): "The kidney and liver abnormalities in the affected lambs were similar to those observed in the Meckel/Joubert/Nephronophthisis constellation of abnormalities in humans."
Pathology: Stayner et al. (2017): "Meckelin protein was expressed in affected and unaffected kidney epithelial cells by immunoblotting, and in primary cilia of lamb kidney cyst epithelial cells by immunofluorescence. In contrast to primary cilia of relatively consistent length and morphology in unaffected kidney cells, those of affected cyst-lining cells displayed a range of short and extremely long cilia, as well as abnormal morphologies, such as bulbous regions along the axoneme. Putative cilia fragments were also consistently located within the cyst luminal contents. The abnormal ciliary phenotype was further confirmed in cultured interstitial fibroblasts from affected kidneys. These primary cilia dysmorphologies and length control defects were significantly greater in affected cells compared to unaffected controls."
Breeds:
Coopworth (Sheep) (VBO_0001380),
Perendale (Sheep) (VBO_0001550).
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 |
|---|---|---|---|---|---|---|
| TMEM67 | transmembrane protein 67 | Ovis aries | 9 | NC_056062.1 (83421974..83377516) | TMEM67 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1042 | Coopworth (Sheep) Perendale (Sheep) | Meckel-like hepatorenal fibrocystic dysplasia syndrome | TMEM67 | haplotype | Naturally occurring variant | Oar_rambouillet_v1.0 | 9 | g.[91651651A>C;91651669A>T] | c.[2042T>A;2060T>G] | p.[(I681N);(I687S)] | Published as c.[2050T>A; 2068T>G]; protein and cDNA positions in the table are based on XP_012039520.2 and XM_012184130.2, respectively. | rs1086155906; rs1088172192 | 2017 | 28487520 | The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries. |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2020). OMIA:002176-9940: 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.
| 2017 | Stayner, C., Poole, C.A., McGlashan, S.R., Pilanthananond, M., Brauning, R., Markie, D., Lett, B., Slobbe, L., Chae, A., Johnstone, A.C., Jensen, C.G., McEwan, J.C., Dittmer, K., Parker, K., Wiles, A., Blackburne, W., Leichter, A., Leask, M., Pinnapureddy, A., Jennings, M., Horsfield, J.A., Walker, R.J., Eccles, M.R. : |
| An ovine hepatorenal fibrocystic model of a Meckel-like syndrome associated with dysmorphic primary cilia and TMEM67 mutations. Sci Rep 7:1601, 2017. Pubmed reference: 28487520. DOI: 10.1038/s41598-017-01519-4. | |
| 2005 | Johnstone, AC., Davidson, BI., Roe, AR., Eccles, MR., Jolly, RD. : |
| Congenital polycystic kidney disease in lambs. N Z Vet J 53:307-14, 2005. Pubmed reference: 16220122. DOI: 10.1080/00480169.2005.36565. |
Edit History
- Created by Frank Nicholas on 15 Mar 2019
- Changed by Frank Nicholas on 15 Mar 2019
- Changed by Frank Nicholas on 10 Mar 2020