OMIA:002559-9913 : Persistent truncus arteriosus, GATA6-related in Bos taurus (taurine cattle)
Categories: Cardiovascular system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2022
Species-specific description: Besnard et al. (2022) monitored “sire-family calf mortality within the French and Walloon Holstein populations, and ... [used] this information to detect genetic defects that might have been overlooked by lack of specific symptoms. … After outlining the 5 worst bulls per category, [the authors] ... paid particular attention to the bulls Mo and Pa, because they were half-brothers. Using a battery of approaches, including necropsies, karyotyping, genetic mapping, and whole-genome sequencing, [the authors] ... described 2 new independent genetic defects in their progeny and their molecular etiology. … Pa was found to be mosaic for a dominant de novo nonsense mutation of GATA 6 binding protein (GATA6), causing severe cardiac malformations.”
Mapping: Besnard et al. (2022) "analyzed SNP array genotypes of 14 progeny that died during the preweaning period ... and 189 half-sib controls .... via transmission disequilibrium test. [The authors] ... mapped the TA [truncus arteriosus] locus on BTA24 between positions 19,505,558 (rs453420861) and 37,877,878 (rs723126921) bp on the ARS-UCD1 assembly."
Molecular basis: Whole genome sequencing of an affected animal and comparison to control animals identified "a thymine-to-adenine substitution in exon 2 of GATA6 predicted to introduce a premature stop codon (chr24: g.34,187,181T > A; GATA6 p.K417X)" as likely causal variant (Besnard et al., 2022). The variant was validated in additional animals and "2 orthologous human truncating mutations located closest to the present bovine nonsense variant (pS418fs and pG441X) have been reported to cause exactly the same phenotype" (Besnard et al.; 2022).
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Besnard et al. (2022): "8 [affected calves] showed symptoms compatible with severe heart defects either leading to premature death or justifying euthanasia on humane grounds."
Pathology: Besnard et al. (2022): "Autopsies gave results strikingly similar to the systematic observation of a persistent truncus arteriosus ... , sometimes associated with additional heart septation defects ...."
Holstein Friesian (Cattle) (VBO_0000239).
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|
|GATA6||GATA binding protein 6||Bos taurus||24||NC_037351.1 (34194339..34161968)||GATA6||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|
|1501||Holstein Friesian (Cattle)||Persistent truncus arteriosus||GATA6||nonsense (stop-gain)||Naturally occurring variant||ARS-UCD1.2||24||g.34187181T>A||c.1249A>T||p.K417X||ENSBTAT00000007537.6||2022||36333145|
Cite this entry
|2022||Besnard, F., Leclerc, H., Boussaha, M., Grohs, C., Jewell, N., Pinton, A., Barasc, H., Jourdain, J., Femenia, M., Dorso, L., Strugnell, B., Floyd, T., Danchin, C., Guatteo, R., Cassart, D., Hubin, X., Mattalia, S., Boichard, D., Capitan, A. :|
|Detailed analysis of mortality rates in the female progeny of 1,001 Holstein bulls allows the discovery of new dominant genetic defects. J Dairy Sci , 2022. Pubmed reference: 36333145. DOI: 10.3168/jds.2022-22365.|
- Created by Imke Tammen2 on 20 Jul 2022
- Changed by Imke Tammen2 on 14 Nov 2022
- Changed by Imke Tammen2 on 15 Nov 2022