OMIA:001595-9940 : Brachygnathia, cardiomegaly and renal hypoplasia syndrome in Ovis aries (sheep) |
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 612921 (trait) , 612921 (gene)
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: 2020
Cross-species summary: Short stature syndrome similar to 3M syndrome in humans
Species-specific symbol: BCRHS
History: This lethal disorder was first described by Shariflou et al. (2011). Its clinical signs are well described by its name.
Mapping: By genotyping 10 affected and 27 control Merinos, each with the Illumina Ovine SNP50 BeadChip (yielding 40,899 informative SNPs), Shariflou et al. (2013) used GWAS and homozygosity mapping to locate this disorder to "a region comprising 20 consecutive SNPs spanning 1.1 Mb towards the distal end of chromosome OAR2".
Molecular basis: Woolley et al. (2020) identified eight positional candidate genes in the interval identified by Shariflou et al. (2013) and "Obscurin like cytoskeletal adaptor 1 (OBSL1) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220,472,248delC within OBSL1. Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant." The likely disease-causing variant is predicted to result in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein.
Genetic engineering:
Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2.
Breed:
Merino (Sheep) (VBO_0001508).
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 |
|---|---|---|---|---|---|---|
| OBSL1 | obscurin-like 1 | Ovis aries | 2 | NC_056055.1 (221493937..221466653) | OBSL1 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1242 | Merino (Sheep) | Brachygnathia, cardiomegaly and renal hypoplasia syndrome | OBSL1 | deletion, small (<=20) | Naturally occurring variant | Oar_rambouillet_v1.0 | 2 | g.236304072del | c.1716del | p.(V573Wfs*119) | XM_027965226.1:c.1716delC | 2020 | 32933480 | The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager & Shernae Woolley, EMAI, NSW Department of Primary Industries. 210906 To conform with HGVS notation, FN removed the nucleotide from g.236304072delG and c.1716delC |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2020). OMIA:001595-9940: 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.
| 2020 | Woolley, S.A., Hayes, S.E., Shariflou, M.R., Nicholas, F.W., Willet, C.E., O'Rourke, B.A., Tammen, I. : |
| Molecular basis of a new ovine model for human 3M syndrome-2. BMC Genet 21:106, 2020. Pubmed reference: 32933480. DOI: 10.1186/s12863-020-00913-8. | |
| 2013 | Shariflou, M.R., Wade, C.M., Kijas, J., McCulloch, R., Windsor, P.A., Tammen, I., Nicholas, F.W. : |
| Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Merino sheep maps to a 1.1-megabase region on ovine chromosome OAR2. Anim Genet 44:231-3, 2013. Pubmed reference: 22762779. DOI: 10.1111/j.1365-2052.2012.02392.x. | |
| 2011 | Shariflou, M., Wade, C., Windsor, P., Tammen, I., James, J.W., Nicholas, F.W. : |
| Lethal genetic disorder in Poll Merino/Merino sheep in Australia. Aust Vet J 89:254-9, 2011. Pubmed reference: 21696373. DOI: 10.1111/j.1751-0813.2011.00789.x. |
Edit History
- Created by Frank Nicholas on 03 Aug 2011
- Changed by Frank Nicholas on 06 Jul 2012
- Changed by Frank Nicholas on 26 Aug 2013
- Changed by Imke Tammen2 on 18 Sep 2020
- Changed by Imke Tammen2 on 19 Sep 2020