OMIA:001823-9913 : Haplotype with homozygous deficiency HH2, IFT80-related in Bos taurus (taurine cattle)

Categories: Mortality / aging (incl. embryonic lethal)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 611177 (gene) , 611263 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

Cross-species summary: This phene was previously called ‘Abortion due to halplotype HH2' and has been renamed to ‘Haplotype with homozygous deficiency-HH2, IFT80-related’.

Species-specific name: Haplotype HH2

Species-specific symbol: Hh2

Mapping: Using genotype data from tens of thousands of North American Holsteins, Jerseys and Brown Swiss cattle each genotyped with approximately 50K SNPs on the BovineSNP50 BeadChip, VanRaden et al. (2011) identified five new recessive lethal haplotypes by searching for common haplotypes that are never homozygous in live animals. Three of these haplotypes occur in Holsteins only, and (following a convention proposed by breed-association staff) VanRaden et al. (2011) named them HH1, HH2 and HH3, where the first H stands for Holstein and the second H for haplotype. The disorder described in this OMIA entry is HH2, which is located in chromosome BTA1, at 92-97Mb (UMD 3.0 genome assembly). McClure et al. (2014) refined the mapping of haplotype HH2 on chromosome BTA1 to 94,860,836 to 96,553,339 (UMD3.1).

Molecular basis: In an extensive study involving exome capture and next-gen sequencing, McClure et al. (2014) were not able to discover any potentially causal variant for haplotype HH2. Yang et al. (2021): "Short- and long-read WGS was performed on four carriers and four non-carriers of HH2 to screen for variants in concordance with HH2 haplotype status.Sequence variation analysis revealed five putative functional variants of protein-coding genes, including a frameshift mutation (g.107172616delT) in intraflagellar transport protein 80 (IFT80) gene. Transcriptome analysis of whole blood indicated that no gene exhibited significantly differential expression or allele-specific expression between carriers and non-carriers in the candidate region. This evidence points to g.107172616delT as the highest priority causative mutation for HH2." In presenting "a comprehensive framework for identification and validation of . . . [harmful recessive] genetic defects, including haplotype-based detection, variant selection from sequence data, and validation using knockout embryos", Ortega et al. (2022) confirmed that the IFT80 variant g.107172616delT (OMIA variant 1396) is the cause of homozygous lethality of haplotype HH2, and providing supporting evidence by showing that the development of IFT80-null embryos created via a CRISPR-Cas9 system is arrested at the 8-cell stage, when IFT80 is normally activated. The authors concluded that the "frameshift in IFT80 on chromosome 1 at 107,172,615 bp (p.Leu381fs) disrupts WNT and hedgehog signaling, and is responsible for the death of homozygous embryos".

Breed: Holstein (black and white) (Cattle) (VBO_0000237).
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
IFT80 intraflagellar transport 80 Bos taurus 1 NC_037328.1 (107079005..107210812) IFT80 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 Year Published PubMed ID(s) Acknowledgements
1396 Holstein Friesian (Cattle) Haplotype with homozygous deficiency-HH2 IFT80 deletion, small (<=20) Naturally occurring variant ARS-UCD1.2 1 g.107172616delT c.1140del p.(L381Ffs*3) g.107172616delT rs523422030 2021 34873723 ENSBTAT00000044761.4:c.1140del ENSBTAP00000042227.4:p.Leu381PhefsTer3

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001823-9913: 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.

2024 Khan, M.Y.A., Dai, D., Su, X., Tian, J., Zhou, J., Ma, L., Wang, Y., Wen, W., Zhang, Y. :
Multiplex fluorescent amplification-refractory mutation system PCR method for the detection of 10 genetic defects in Holstein cattle and its comparison with the KASP genotyping assay. Anim Genet , 2024. Pubmed reference: 38622758. DOI: 10.1111/age.13432.
2023 Ask-Gullstrand, P., Strandberg, E., Båge, R., Rius-Vilarrasa, E., Berglund, B. :
The effect of genetic defects on pregnancy loss in Swedish dairy cattle. J Dairy Sci , 2023. Pubmed reference: 37977438. DOI: 10.3168/jds.2023-24159.
2022 Ortega, M.S., Bickhart, D.M., Lockhart, K.N., Null, D.J., Hutchison, J.L., McClure, J.C., Cole, J.B. :
Truncation of IFT80 causes early embryonic loss in Holstein cattle associated with Holstein haplotype 2. J Dairy Sci , 2022. Pubmed reference: 36085107. DOI: 10.3168/jds.2022-21853.
2021 Yang, Y., Si, J., Lv, X., Dai, D., Liu, L., Tang, S., Wang, Y., Zhang, S., Xiao, W., Zhang, Y. :
Integrated analysis of whole genome and transcriptome sequencing reveals a frameshift mutation associated with recessive embryonic lethality in Holstein cattle. Anim Genet , 2021. Pubmed reference: 34873723. DOI: 10.1111/age.13160.
2016 Cole, J.B., Null, D.J., VanRaden, P.M. :
Phenotypic and genetic effects of recessive haplotypes on yield, longevity, and fertility. J Dairy Sci 99:7274-88, 2016. Pubmed reference: 27394947. DOI: 10.3168/jds.2015-10777.
Segelke, D., Täubert, H., Reinhardt, F., Thaller, G. :
Considering genetic characteristics in German Holstein breeding programs. J Dairy Sci 99:458-67, 2016. Pubmed reference: 26601581. DOI: 10.3168/jds.2015-9764.
2014 McClure, M.C., Bickhart, D., Null, D., Vanraden, P., Xu, L., Wiggans, G., Liu, G., Schroeder, S., Glasscock, J., Armstrong, J., Cole, J.B., Van Tassell, C.P., Sonstegard, T.S. :
Bovine exome sequence analysis and targeted SNP genotyping of recessive fertility defects BH1, HH2, and HH3 reveal a putative causative mutation in SMC2 for HH3. PLoS One 9:e92769, 2014. Pubmed reference: 24667746. DOI: 10.1371/journal.pone.0092769.
2011 VanRaden, P.M., Olson, K.M., Null, D.J., Hutchison, J.L. :
Harmful recessive effects on fertility detected by absence of homozygous haplotypes. J Dairy Sci 94:6153-61, 2011. Pubmed reference: 22118103. DOI: 10.3168/jds.2011-4624.

Edit History

  • Created by Frank Nicholas on 12 Jun 2013
  • Changed by Frank Nicholas on 12 Jun 2013
  • Changed by Frank Nicholas on 01 Apr 2014
  • Changed by Frank Nicholas on 24 Mar 2015
  • Changed by Imke Tammen2 on 16 Dec 2021
  • Changed by Frank Nicholas on 14 Sep 2022
  • Changed by Frank Nicholas on 15 Sep 2022