OMIA 000424-9913 : Goitre, familial in Bos taurus

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

Possibly relevant human trait(s) and/or gene(s) (MIM number): 274700

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1987

Cross-species summary: Enlargement of the thyroid gland, causing a swelling in the front of the neck. Familial forms of this disorder have been identified in several species. But only in cattle and goats has the molecular basis been determined. 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).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TG thyroglobulin Bos taurus 14 NC_037341.1 (8453438..8217497) TG 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
Afrikander Goitre, familial TG nonsense (stop-gain) UMD 3.1 14 g. 9487845C>T c.1963C>T p.R655* rs480120030 1987 3472203 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
2010 Watson, PJ., Scholes, SF. :
Congenital goitre and alopecia in pedigree Saler cattle. Vet Rec 166:29-30, 2010. Pubmed reference: 20045861. DOI: 10.1136/vr.b5598.
2006 Rivolta, C.M., Targovnik, H.M. :
Molecular advances in thyroglobulin disorders. Clin Chim Acta 374:8-24, 2006. Pubmed reference: 16870170. DOI: 10.1016/j.cca.2006.05.043.
1997 Wither, S.E. :
Congenital goiter in cattle Canadian Veterinary Journal - Revue Veterinaire Canadienne 38:178, 1997.
1993 Medeiros-Neto, G., Targovnik, H.M., Vassart, G. :
Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism. Endocr Rev 14:165-83, 1993. Pubmed reference: 8325250.
Mee, J.F. :
Goitre in Stillborn Calves Veterinary Record 133:404, 1993. Pubmed reference: 8310613.
1990 Ricketts, M.H., Vandenplas, S. :
DNA screening for hereditary goitre in Afrikander cattle. J S Afr Vet Assoc 61:9-10, 1990. Pubmed reference: 2269992.
1988 Hansen, C., Gerard, C., Vassart, G., Stordeur, P., Christophe, D. :
Thyroid-specific and cAMP-dependent hypersensitive regions in thyroglobulin gene chromatin. Eur J Biochem 178:387-93, 1988. Pubmed reference: 2850177.
1987 De Martynoff, G., Pohl, V., Mercken, L., van Ommen, GJ., Vassart, G. :
Structural organization of the bovine thyroglobulin gene and of its 5'-flanking region. Eur J Biochem 164:591-9, 1987. Pubmed reference: 3032624.
Ricketts, M.H., Simons, M.J., Parma, J., Mercken, L., Dong, Q., Vassart, G. :
A nonsense mutation causes hereditary goitre in the Afrikander cattle and unmasks alternative splicing of thyroglobulin transcripts Proceedings of the National Academy of Sciences of the United States of America 84:3181-3184, 1987. Pubmed reference: 3472203.
1985 Mercken, L., Simons, MJ., De Martynoff, G., Swillens, S., Vassart, G. :
Presence of hormonogenic and repetitive domains in the first 930 amino acids of bovine thyroglobulin as deduced from the cDNA sequence. Eur J Biochem 147:59-64, 1985. Pubmed reference: 3855750.
Mercken, L., Simons, MJ., Swillens, S., Massaer, M., Vassart, G. :
Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA. Nature 316:647-51, 1985. Pubmed reference: 3855243.
Ricketts, M.H., Pohl, V., Martynoff, G. de, Boyd, C.D., Bester, A.J., Jaarsveld, P.P. van, Vassart, G. :
Defective splicing of thyroglobulin gene transcripts in the congenital goitre of the Afrikander cattle EMBO Journal 4:731-737, 1985. Pubmed reference: 2988933.
Ricketts, M.H., Schulz, K., Zyl, A. van, Bester, A.J., Boyd, C.D., Meinhold, W., van Jaarsveld, P.P. :
Autosomal recessive inheritance of congenital goitre in Afrikander cattle Journal of Heredity 76:12-16, 1985. Pubmed reference: 3980970.
Ricketts, M.H., Vanderplas, S., Walt, M. van der, Jaarsveld, P.P. van, Bester, A.J., Boyd, C.D. :
Afrikander cattle congenital goiter: size heterogeneity in thyroglobulin mRNA Biochem. Biophys. Research Communcation 126:240-246, 1985.
1984 Tassi, V.P.N., Lauro, R. di, Jaarsveld, P.P. van, Alvino, C.G. :
Two abnormal thyroglobulin-like polypeptides are produced from Afrikander cattle congenital goitre mRNA Journal of Biological Chemistry 259:10507-10510, 1984. Pubmed reference: 6469973.
1983 Schulz, KC., Groenewald, JW. :
The familial incidence of "grey" Afrikander calves with and without goitre. J S Afr Vet Assoc 54:147-54, 1983. Pubmed reference: 6655652.
1982 Mercken, L., Simons, MJ., Vassart, G. :
The 5'-end of bovine thyroglobulin mRNA encodes a hormonogenic peptide. FEBS Lett 149:285-7, 1982. Pubmed reference: 7152045.
1981 Holmes, J.H., Humphrey, J.D., Walton, E.A., O'Shea, J.D. :
Cataracts, goitre and infertility in cattle grazed on an exclusive diet of Leucaena leucocephala. Aust Vet J 57:257-61, 1981. Pubmed reference: 7316890.
1978 Pammenter, M., Albrecht, C., Liebenberg, N.v.D.W. van, Jaarsveld, P. :
Afrikander cattle congenital goiter: characteristics of its morphology and iodoprotein pattern Endocrinology 102:954-965, 1978. Pubmed reference: 744001.
1962 Schulz, K.C.A. :
[First report of familial goitre in Afrikander cattle] Proceedings of the Second Congress of the South African Genetics Society, Victoria, October 1-4 :90-92 (abstract), 1962.

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  • Created by Frank Nicholas on 10 Sep 2005
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