OMIA:001686-9913 : Dwarfism, proportionate, with inflammatory lesions in Bos taurus (taurine cattle)
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s) (MIM number): 612598 (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: 2012
History: The history of RING fingers is most unusual. In 1991 Hanson et al. (Genomics, 10, 417-424) reported the discovery of four new genes of unknown function within the human major histocompatibility complex (HLA), which is the "engine room" of the immune response. These four new genes were designated RING 1-4, where RING stood for Really Interesting New Gene! Two years later, Lovering et al. (1993; PNAS 90, 2112-2116) reported that these genes encode a zinc-finger-like protein motif that occurs in many proteins and which is associated with DNA binding. Not surprisingly, they named this motif the "RING finger"! Now, with the report by Sartelet et al. (2012), we have the first case of a disorder resulting from a mutation in a RING finger gene.
Inheritance: This form of proportionate dwarfism is autosomal recessive. However, because up to 1/3 of affected calves die of severe inflammation (mainly pneumonia) within 6 months of birth, the expected autosomal recessive segregation ratios are not seen in surviving dwarf calves (Sartelet et al., 2012). The disorder is lethal in the sense that affected animals are never bred.
Molecular basis: Sartelet et al. (2012) identified the causative mutation as a "c124-2A>G splice variant in intron 1 of the RNF11 gene". This gene encodes RING finger protein 11, which is a key regulator in the A20 complex of the inflammatory response.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Prevalence: Sartelet et al. (2012) reported the surprising result "that 26% of healthy Belgian Blue animals" are carriers of the mutant allele, corresponding to a mutant-allele frequency of 13%. This is extraordinalrily high for an allele that is, in effect, lethal. These same authors provided evidence supporting selection favouring heterozygotes as being the most likely explanation. The traits undergoing such selection remain to be determined.
Belgian Blue (Cattle) (VBO_0000139).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RNF11||ring finger protein 11||Bos taurus||3||NC_037330.1 (95059039..95012093)||RNF11||Homologene, Ensembl , NCBI gene|
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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|
|376||Belgian Blue (Cattle)||Dwarfism, proportionate, with inflammatory lesions||RNF11||splicing||Naturally occurring variant||ARS-UCD1.2||3||g.95015373T>C||c.124-2A>G||NM_001077953.1||rs3423159409||2012||22438830||Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)|
Cite this entry
|2012||Sartelet, A., Druet, T., Michaux, C., Fasquelle, C., Géron, S., Tamma, N., Zhang, Z., Coppieters, W., Georges, M., Charlier, C. :|
|A splice site variant in the bovine RNF11 gene compromises growth and regulation of the inflammatory response. PLoS Genet 8:e1002581, 2012. Pubmed reference: 22438830. DOI: 10.1371/journal.pgen.1002581.|
- Created by Frank Nicholas on 24 Jan 2012
- Changed by Frank Nicholas on 25 Jan 2012
- Changed by Frank Nicholas on 11 Jul 2017