OMIA 001939-9913 : Abortion due to haplotype BH2 in Bos taurus

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

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).

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.

Breed: Brown Swiss.

Associated gene:

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

Variants

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Brown Swiss Abortion due to haplotype BH2 TUBD1 missense UMD3.1 19 g.11063520T>C c.757T>C p.H210R 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

References


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.
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. et al. :
A missense mutation in TUBD1 is associated with high juvenile mortality in Braunvieh and Fleckvieh cattle BioRchiv :, 2016. DOI: 10.1101/041921 .
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.
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.

Edit History


  • Created by Frank Nicholas on 31 Oct 2014
  • Changed by Frank Nicholas on 31 Oct 2014
  • Changed by Frank Nicholas on 24 Mar 2015
  • Changed by Frank Nicholas on 03 Mar 2016
  • Changed by Frank Nicholas on 04 Mar 2016
  • Changed by Frank Nicholas on 02 Jun 2016