OMIA:001817-9913 : Perinatal weak calf syndrome in Bos taurus (taurine cattle)

Categories: Mortality / aging (incl. embryonic lethal)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600709 (gene) , 617093 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

History: This disorder was first reported by Ogata et al. (1999).

Mapping: Hirano et al. (2013) conducted a genome scan on 30 affected and 30 normal offspring of a bull with an abnormally high incidence of this disorder, each offspring and the bull being genotyped with BovineSNP50 BeadChip, yielding 13,208 informative SNPs. Homozygosity mapping (supported by linkage mapping on the candidate chromosome) implicated a 4.04Mb region on chromosome BTA8, encompassing 29 annotated genes.

Molecular basis: Exome sequencing in the candidate region (see Mapping section) of 2 affected, one carrier and one homozygous normal animal enabled Hirano et al. (2013) to identify the causal mutation as a missense mutation (c.235G>C; p.Val79Leu) in the IARS gene which encodes isoleucyl-tRNA synthetase. Hirano et al. (2016) reported that "the [above] homozygous IARS mutation not only causes calf death, but also embryonic or fetal death.

Clinical features: This disorder is characterised by "neonatal weakness with intrauterine growth retardation" (Hirano et al., 2013). Islam et al. (2021): "There were no statistically significant differences between the carrier and wild-type cows with respect to either [metabolic profile test] MPT results or reproductive performance, indicating that the carrier cows have necessary IARS activity to maintain minimal health and reproductive potential."

Prevalence: Islam et al. (2021): "In 2009 and 2018, DNA samples were collected from 130 and 462 clinically healthy JB cows, respectively, in Kagoshima prefecture. ... Genotyping [for the c.235G>C mutation] revealed that the carrier rate was 6.9% in 2009 and 1.5% in 2018".

Control: Ikeda et al. (2017) reported the repair of the IARS likely causal variant in day-34 foetuses, following CRISPR/Cas9-assisted editing of "fetal fibroblast (BFF) cells isolated from a homozygous mutant calf".

Breed: Japanese Black, Japan (Cattle) (VBO_0004987).
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:

Symbol Description Species Chr Location OMIA gene details page Other Links
IARS isoleucyl-tRNA synthetase Bos taurus 8 NC_037335.1 (83918584..83837391) IARS Homologene, Ensembl , NCBI gene


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.

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 Year Published PubMed ID(s) Acknowledgements
204 Japanese Black, Japan (Cattle) Perinatal weak calf syndrome IARS missense Naturally occurring variant ARS-UCD1.2 8 g.83909754C>G c.235G>C p.(V79L) 2013 23700453 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001817-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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 Kalotay, E., Klugmann, M., Housley, G.D., Fröhlich, D. :
Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models. Front Neurosci 17:1182874, 2023. Pubmed reference: 37274208. DOI: 10.3389/fnins.2023.1182874.
2021 Islam, M.S., Shinya, U., Takagi, M., Akahoshi, T., Yabuki, A., Pervin, S., Rakib, T.M., Rahman, M.M., Tacharina, M.R., Yamato, O. :
Carrier rate of the c.235G>C mutation in the bovine isoleucyl-tRNA synthetase (IARS) gene of Japanese Black cows at Kagoshima prefecture, Japan, and analysis of the metabolic profiling and reproductive performance of heterozygous cows. J Vet Med Sci 83:254-259, 2021. Pubmed reference: 33298632. DOI: 10.1292/jvms.20-0356.
Sasaki, S., Watanabe, T., Ibi, T., Hasegawa, K., Sakamoto, Y., Moriwaki, S., Kurogi, K., Ogino, A., Yasumori, T., Wakaguri, H., Muraki, E., Miki, Y., Yoshida, Y., Inoue, Y., Tabuchi, I., Iwao, K., Arishima, T., Kawashima, K., Watanabe, M., Sugano, S., Sugimoto, Y., Suzuki, Y. :
Identification of deleterious recessive haplotypes and candidate deleterious recessive mutations in Japanese Black cattle. Sci Rep 11:6687, 2021. Pubmed reference: 33758295. DOI: 10.1038/s41598-021-86225-y.
Singh, P., Ali, S.A. :
Impact of CRISPR-Cas9-based genome engineering in farm animals. Vet Sci 8:122, 2021. Pubmed reference: 34209174. DOI: 10.3390/vetsci8070122.
2019 Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A., Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A. :
Screening genetic diseases prevalence in Braunvieh cattle. Trop Anim Health Prod 51:25-31, 2019. Pubmed reference: 30014197. DOI: 10.1007/s11250-018-1655-y.
2017 Hirano, T., Nishimura, S., Hara, H., Sugimoto, Y., Hanzawa, K. :
Mapping of calf death in Japanese Black cattle. Anim Biotechnol :1-6, 2017. Pubmed reference: 28103142. DOI: 10.1080/10495398.2016.1267643.
Ikeda, M., Matsuyama, S., Akagi, S., Ohkoshi, K., Nakamura, S., Minabe, S., Kimura, K., Hosoe, M. :
Correction of a disease mutation using CRISPR/Cas9-assisted genome editing in Japanese Black cattle. Sci Rep 7:17827, 2017. Pubmed reference: 29259316. DOI: 10.1038/s41598-017-17968-w.
2016 Hirano, T., Matsuhashi, T., Takeda, K., Hara, H., Kobayashi, N., Kita, K., Sugimoto, Y., Hanzawa, K. :
IARS mutation causes prenatal death in Japanese Black cattle. Anim Sci J 87:1178-81, 2016. Pubmed reference: 27229878. DOI: 10.1111/asj.12639.
2013 Hirano, T., Kobayashi, N., Matsuhashi, T., Watanabe, D., Watanabe, T., Takasuga, A., Sugimoto, M., Sugimoto, Y. :
Mapping and exome sequencing identifies a mutation in the IARS gene as the cause of hereditary perinatal weak calf syndrome. PLoS One 8:e64036, 2013. Pubmed reference: 23700453. DOI: 10.1371/journal.pone.0064036.
2008 Takasu, M., Shirota, K., Ohba, Y., Nishii, N., Murase, T., Miyazawa, K., Kitagawa, H. :
Thymic hypoplasia in Japanese black calves with stillbirth/perinatal weak calf syndrome. J Vet Med Sci 70:1173-7, 2008. Pubmed reference: 19057134.
1999 Ogata, Y., Nakao, T., Takahashi, K., Abe, H., Misawa, T., Urushiyama, Y., Sakai, J. :
Intrauterine growth retardation as a cause of perinatal mortality in Japanese black beef calves. Zentralbl Veterinarmed A 46:327-34, 1999. Pubmed reference: 10481611.

Edit History

  • Created by Frank Nicholas on 05 Jun 2013
  • Changed by Frank Nicholas on 05 Jun 2013
  • Changed by Frank Nicholas on 27 Aug 2017
  • Changed by Frank Nicholas on 21 Sep 2019
  • Changed by Imke Tammen2 on 18 Dec 2020
  • Changed by Imke Tammen2 on 06 Aug 2021
  • Changed by Imke Tammen2 on 11 Aug 2021
  • Changed by Imke Tammen2 on 17 Feb 2023