OMIA 001686-9913 : Dwarfism, proportionate, with inflammatory lesions in Bos taurus

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.

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.

Breed: Belgian Blue.

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Belgian Blue Dwarfism, proportionate, with inflammatory lesions RNF11 splicing UMD3.1 3 g.95601696A>G c.124-2A>G 2012 22438830 Breed and variant 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)

Reference


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.

Edit History


  • Created by Frank Nicholas on 24 Jan 2012
  • Changed by Frank Nicholas on 25 Jan 2012
  • Changed by Frank Nicholas on 11 Jul 2017