OMIA:001009-9913 : Hemimelia, tibial in Bos taurus (taurine cattle)
In other species: indicine cattle (zebu)
Categories: Limbs / fins / digit / tail phene
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
Species-specific description: See also: 'OMIA:001009-9915 : Hemimelia, tibial in Bos indicus'
History: This disorder was first reported (in Galloways) in the UK by Young (1951) and in the USA and Germany by Ojo et a. (1974).
Mapping: Chromosome BTA15
Molecular basis: Deletion: around 45,694 bp including exon 1 of ALX4 of Shorthorns (Beever and Marron, 2012)
Duplication: 20bp duplication in exon 2 of ALX4 of Galloways; g.75154399_75154418dup (AC_000172; UMD3.1), creating a frameshift (Brenig et al., 2015)
Buitkamp et al. (2022) reported a 20-bp duplication in the ALX4 gene (called ALX4dup-LfL) as being the likely cause of the case of tibial hemimelia in a white Galloway calf born in Germany. These authors note that the likely causal variant reported by Brenig et al. (2015) (called ALX4dup-GAU) corresponds "exactly to the last 20 bp of exon 2, whereas the ALX4dup-LfL is shifted by 3 bp in the 5-prime direction".
Control: In the 1970s, the Galloway Cattle Society in Great Britain instigated what became a text-book example of how to control an autosomal-recessive disorder for which there was (at that time) no blood-based genotype test (Nicholas, 1987). The control programme comprised:
1. Maintaining a register of carriers, i.e. bulls and cows that had produced at least one affected calf
2. An insurance scheme, in which the purchaser of a young bull at any official breed society sale was insured against that young bull throwing affected offspring within 21 months following the sale (9 months gestation and 12 months use). It was compulsory for all young bulls sold at official sales to be insured, the vendor being obliged to pay the premium.
3. Maintaining a test herd of known carrier cows, through which young bulls could be progeny-tested for this disorder. The effectiveness of this progeny-testing was enhanced by the use of early pregnancy termination, made feasible by the disorder being visible in 90-day embryos (Pollock et al., 1979).
Genetic testing: A DNA test for this disorder in Shorthorns was described in 2006 in a patent published in 2012 (Beever and Marron, 2012).
Galloway (Cattle) (VBO_0000207),
Shorthorn (Cattle) (VBO_0000375).
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|
|ALX4||ALX homeobox 4||Bos taurus||15||NC_037342.1 (74417594..74373004)||ALX4||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|
|764||Shorthorn (Cattle)||Tibial hemimelia||ALX4||deletion, gross (>20)||Naturally occurring variant||15||Deletion of 45,694 bp including exon 1 of ALX4||2012||Reference not in PubMed; see OMIA 001009-9913 for reference details|
|763||Galloway (Cattle)||Tibial hemimelia||ALX4||ALX4dup-GAU||duplication||Naturally occurring variant||ARS-UCD1.2||15||g.74384916_74384935dup||UMD3.1 position is g.75154399_75154418dup. Duplication of 20bp in exon 2 is predicted to result in a frameshift leading to a premature stop codon and truncated protein.||2015||26076463||The genomic location on ARS-UCD1.2 was determined by Katie Eager and Shernae Woolley, EMAI, NSW. Department of Primary Industries. The same ARS-UCD1.2 location in the reverse order was included in the paper by Buitkamp et al. (2022). The allele name ALX4dup-GAU was also given by Buitkamp et al. (2022).|
|1516||Galloway (Cattle)||Tibial hemimelia||ALX4||ALX4dup-LfL||duplication||Naturally occurring variant||ARS-UCD1.2||15||g.74384938_74384919dup||Buitkamp et al. (2022): "The ALX4dup-LfL duplication results in a frameshift (amino acid position 151) leading to a truncated protein of 248 nt in length, compared with 303 nt of the wild-type protein (XP_027418402.1)".||2023||36585373|
Cite this entry
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.
|2023||Buitkamp, J., Semmer, J., Schmaußer, M., Schade, B. :|
|A case of tibial hemimelia in a German Galloway calf is associated with a novel mutation in the ALX4 gene. Anim Genet 54:220-221, 2023. Pubmed reference: 36585373 . DOI: 10.1111/age.13290.|
|2015||Brenig, B., Schütz, E., Hardt, M., Scheuermann, P., Freick, M. :|
|A 20 bp duplication in exon 2 of the aristaless-like homeobox 4 gene (ALX4) is the candidate causative mutation for tibial hemimelia syndrome in Galloway cattle. PLoS One 10:e0129208, 2015. Pubmed reference: 26076463 . DOI: 10.1371/journal.pone.0129208.|
|2012||Beever, J.E., Marron, B.M. :|
|Screening for the genetic defect causing tibial hemimelia in bovines. US Patent 8158356 B2 :, 2012.|
|2008||Whitlock, BK., Kaiser, L., Maxwell, HS. :|
|Heritable bovine fetal abnormalities. Theriogenology 70:535-49, 2008. Pubmed reference: 18514810 . DOI: 10.1016/j.theriogenology.2008.04.016.|
|2005||Marron, B.M., Thurnau, G., Hannon, C.P., Beever, J.E. :|
|Mapping of the locus causing tibial hemimelia (TH) in Shorthorn cattle. Plant & Animal Genomes XIII Conference :P534, 2005.|
|2000||Lapointe, J.M., Lachance, S., Steffen, D.J. :|
|Tibial hemimelia, meningocele, and abdominal hernia in Shorthorn cattle Veterinary Pathology 37:508-511, 2000. Pubmed reference: 11055885 .|
|1987||Nicholas, F.W. :|
|Veterinary Genetics. Oxford University Press, Oxford :, 1987.|
|1982||Salako, MA., Abdullahi, US. :|
|Tibial hemimelia in a Bunaji calf. Vet Rec 110:430, 1982. Pubmed reference: 7090160 .|
|1979||Pollock, DL., Fitzsimons, J., Deas, WD., Fraser, JA. :|
|Pregnancy termination in the control of the tibial hemimelia syndrome in Galloway cattle. Vet Rec 104:258-60, 1979. Pubmed reference: 473505 .|
|1978||Leipold, H.W., Saperstein, G., Swanson, R., Guffy, M.M., Schalles, R. :|
|Inheritance of tibial hemimelia in Galloway cattle. Zeitschrift fuer Tierzuechtung und Zuechtungsbiologie 94:291-295, 1978.|
|1977||Guffy, M.M., Leipold, H.N. :|
|Radiological diagnosis of economically important genetic defects in cattle Journal of the American Veterinary Radiology Society 18:109-116, 1977.|
|Leipold, H.W., Guffy, M.M., Cook, J.E. :|
|Tibial hemimelia in Galloway cattle. Comparative Pathology Bulletin 9:2-, 1977.|
|1976||Young, G.B. :|
|Some genetic defects in British livestock and their control Animal Breeding Research Organisation. Annual Report :31-35, 1976.|
|1974||Ojo, SA., Guffy, MM., Saperstein, G., Leipold, HW. :|
|Tibial hemimelia in Galloway calves. J Am Vet Med Assoc 165:548-50, 1974. Pubmed reference: 4416648 .|
|1951||Young, GB. :|
|A case of tibial hemimelia in cattle. Br Vet J 107:23-8, 1951. Pubmed reference: 14812141 .|
- Created by Frank Nicholas on 30 Mar 2011
- Changed by Frank Nicholas on 15 Aug 2012
- Changed by Frank Nicholas on 21 Jun 2015
- Changed by Frank Nicholas on 03 Jan 2023
- Changed by Imke Tammen2 on 19 Jun 2023