OMIA:001939-9913 : Haplotype with homozygous deficiency BH2, TUBD1-related in Bos taurus (taurine cattle)
Categories: Mortality / aging (incl. embryonic lethal)
Possibly relevant human trait(s) and/or gene(s) (MIM number): 607344 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive lethal
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2016
Cross-species summary: Phenes previously called ‘Abortion due to halplotype ….. ’ or ‘Abortion (embryonic lethality)’ , have been renamed to ‘Haplotype with homozygous deficiency, …’ or a phene name that is descriptive of the phenotype observed in homozygous affected animals [14/1/2022]
Species-specific symbol: BH2
History: After consultation with Schwarzenbacher and colleagues, this haplotype was named BH2 (Braunvieh haplotype 2) by VanRaden et al. (2013). It was previously called 424.49 by Vanraden et al. (2011) and BTA19-1 by Schwarzenbacher et al. (2012).
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 potential recessive lethal haplotypes by searching for common haplotypes that are never homozygous in live animals. One of these haplotypes (424.49) was roughly mapped to the region 7-16Mb on chromosome BTA19), but was not pursued further, by VanRaden et al. (2011). A subsequent study of another 2,959 Brown Swiss from Austria and Germany enabled Schwarzenbacher et al. (2012) to confirm the existence of this lethal haplotype and to refine its location to a region 10.140-11.049Mb on BTA19. However, its effect was still not clear: these authors noted that this haplotype "is suspect and needs further research". FN thanks Cole et al. (2014) for alerting him to the latter results.
In a preprint posted on the Cold Spring Harbor bioRxiv preprint server on 1st March 2016, Schwarzenbacher et al. (2016) documented the quite marked effects of this haplotype on mortality, and reported the discovery of its causal mutation as "a missense mutation in TUBD1 (rs383232842[T>C], p.H210R)". This is the first result from a preprint to be included in OMIA. A refereed version of this paper was published three months later in BMC Genomics (see reference list).
Häfliger et al. (2021) identified the same haplotype and same likely causal variant in Brown Swiss cattle in their investigation of Brown Swiss and Original Braunvieh populations reared in Switzerland - see OMIA002513-9913 for more detail.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: As reported by Schwarzenbacher et al. (2016),"Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia." As pointed out carefully by Schwarzenbacher et al. (2016), not all homozygotes die, i.e. the lethal allele has incomplete penetrance.
Prevalence: Wu et al. (2020) reported the frequency for this lethal haplotype as 4.4% in 19,309 Nordic Red Dairy cattle. Noting an inconsistency in this breed between the occurrence of the lethal haplotype and the likely causal variant (p.H210R) in Brown Swiss reported by Schwarzenbacher et al. (2016), Wu et al. (2020) noted that "it is highly likely that an additional recessive lethal mutation is segregating in this region in" Nordic Red Dairy cattle.
Brown Swiss (Cattle) (VBO_0000166),
Nordic Red (Cattle) (VBO_0016847).
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|
|TUBD1||tubulin delta 1||Bos taurus||19||NC_037346.1 (10840880..10816976)||TUBD1||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|
|776||Brown Swiss (Cattle) Simmental (Cattle)||Haplotype with homozygous deficiency BH2||TUBD1||missense||Naturally occurring variant||ARS-UCD1.2||19||g.10833921T>C||c.757T>C||p.(H210R)||rs383232842||rs383232842||2016||27225349||Some variant information kindly provided or confirmed by Hubert Pausch, including information from Additional Table 6 of Jansen et al. (2013) BMC Genomics201314:446 https://doi.org/10.1186/1471-2164-14-446|
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||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.|
|2021||Häfliger, I.M., Seefried, F.R., Spengeler, M., Drögemüller, C. :|
|Mining massive genomic data of two Swiss Braunvieh cattle populations reveals six novel candidate variants that impair reproductive success. Genet Sel Evol 53:95, 2021. Pubmed reference: 34915862. DOI: 10.1186/s12711-021-00686-3.|
|2020||Wu, X., Mesbah-Uddin, M., Guldbrandtsen, B., Lund, M.S., Sahana, G. :|
|Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle. J Dairy Sci 103:4570-4578, 2020. Pubmed reference: 32197842. DOI: 10.3168/jds.2019-17831.|
|2016||Biscarini, F., Schwarzenbacher, H., Pausch, H., Nicolazzi, E.L., Pirola, Y., Biffani, S. :|
|Use of SNP genotypes to identify carriers of harmful recessive mutations in cattle populations. BMC Genomics 17:857, 2016. Pubmed reference: 27809787. DOI: 10.1186/s12864-016-3218-9.|
|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.|
|Schwarzenbacher, H., Burgstaller, J., Seefried, F.R., Wurmser, C., Hilbe, M., Jung, S., Fuerst, C., Dinhopl, N., Weissenböck, H., Fuerst-Waltl, B., Dolezal, M., Winkler, R., Grueter, O., Bleul, U., Wittek, T., Fries, R., Pausch, H. :|
|A missense mutation in TUBD1 is associated with high juvenile mortality in Braunvieh and Fleckvieh cattle. BMC Genomics 17:400, 2016. Pubmed reference: 27225349. DOI: 10.1186/s12864-016-2742-y.|
|Schwarzenbacher, H. et al. :|
|A missense mutation in TUBD1 is associated with high juvenile mortality in Braunvieh and Fleckvieh cattle BioRchiv , 2016. DOI: 10.1101/041921 .|
|2014||Cole, J.B., VanRaden, P.M., Null, D.J., Hutchison, J.L., Cooper, T.A., Hubbard, S.M. :|
|Haplotype tests for recessive disorders that affect fertility and other traits. AIP RESEARCH REPORT GENOMIC3 (09-13); http://aipl.arsusda.gov/reference/recessive_haplotypes_ARR-G3.html , 2014.|
|2013||VanRaden, P., Null, D., Hutchison, J., Cooper, T. :|
|New fertility and stillbirth haplotypes and changes in haplotype status Website of the Council on Dairy Cattle Breeding: https://www.cdcb.us/reference/changes/eval1308.htm , 2013.|
|2012||Schwarzenbacher, H., Fuerst, C., Fuerst-Waltl, B., Dolezal, M. :|
|A genome-wide search for harmful recessive haplotypes in Brown Swiss and Fleckvieh cattle. EAAP annual meeting; http://old.eaap.org/Previous_Annual_Meetings/2012Bratislava/Papers/Published/22_Schwarzenbacher.pdf :Abstract p. 171, 2012.|
|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.|
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