In other species: chicken , dog , American black bear , domestic cat , pig , goat , sheep , golden hamster , bongo , water buffalo

Categories: Endocrine / exocrine gland phene (incl mammary gland)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 274700 (trait) , 188450 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0010135: thyroid dyshormonogenesis 3

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Disease-related: yes

Key variant known: yes

Year key variant first reported: 1987

Cross-species summary: Goitre is the enlargement of the thyroid gland, causing a swelling in the front of the neck. The condition can develop due to nutritional iodine deficiencies but familial forms of this disorder have been identified in several species. The molecular basis been determined for familial goitre in cattle and goats. Also spelt goiter.

History: This disorder is the first in any domesticated animal species to be characterised at the DNA level.

Molecular basis: The causative mutation for this disorder was discovered via the candidate gene approach. Tassi et al. (1984) reported a 10-15-fold decrease in the concentration of TG mRNA in affected cattle; Ricketts et al. (1985) reported the use of S1 nuclease assays and electron microscopy to narrow down the location of the mutation to the junction of exon 9 and intron 9; and Ricketts et al. (1987) reported the use of cloning and sequencing of genomic DNA from affected and normal animals to discover the causal mutation: a C>T transition creating a stop codon at position 697 in exon 9. Interestingly, both normal and affected cattle produce a second, shortened TG transcript that lacks exon 9. The sequences obtained from normal (European) and mutant (Afrikander) genes also differ by a missense mutation at codon 699 (A>G; Ala>Gly; a conservative amino acid change) and a A>G transition 25 bases into intron 9. It is not known whether these polymorphisms exist within the Afrikander breed. The intronic transition generates a Pst recognition site.

Genetic testing: The C>T transition removes a recognition sequence for the restriction enzyme TaqI, thereby providing a genotyping test based on the actual causative mutation (Ricketts et al., 1987).

Breeds: Africander (Cattle) (VBO_0000094), Blanco Orejinegro, Colombia (Cattle) (VBO_0004602), Salers (Cattle) (VBO_0000366).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: