OMIA 001941-9913 : Abortion due to haplotype HH5 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 name: Haplotype HH5

Species-specific symbol: HH5

Species-specific description: [FN thanks Ekkehard Schütz for feedback on an earlier version of the text on this page]

Mapping: Using a strategy similar to that of VanRaden et al. (2011), Cooper et al. (2013) discovered reduced-fertility haplotype HH5, located on chromosome BTA9.

In their table of reduced-fertility haplotypes, Cole et al. (2014) list this haplotype as being located at 92,350,052 – 93,910,957bp on chromosome BTA9.

Schütz et al. (2016) fine-mapped the likely causal region of HH5 to be "an approximately 138kb region spanning 93.233Mb to 93.371Mb".

Molecular basis: Schütz et al. (2016) identified the likely causal mutation as "a deletion of 138kbp, spanning position 93,233kb to 93,371kb on chromosome 9 (BTA9), harboring only dimethyl-adenosine transferase 1 (TFB1M). The deletion breakpoints are flanked by bovine long interspersed nuclear elements Bov-B (upstream) and L1ME3 (downstream), suggesting a homologous recombination/deletion event. TFB1M di-methylates adenine residues in the hairpin loop at the 3’-end of mitochondrial 12S rRNA, being essential for synthesis and function of the small ribosomal subunit of mitochondria." The causality of this deletion is reinforced by the fact that homozygous TFB1M knockout mice are not viable and suffer fetal death (Schütz et al., 2016).

Prevalence: Using direct PCR for the deletion, Schütz et al (2016) estimated the prevalence of carriers to be 5.5% in the interrogated German Holstein population.

Breed: Holstein.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TFB1M transcription factor B1, mitochondrial Bos taurus 9 NC_037336.1 (91932613..91865417) TFB1M 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
Holstein Abortion due to haplotype HH5 TFB1M complex rearrangement "a deletion of 138kbp, spanning position 93,233kb to 93,371kb on chromosome 9 (BTA9), harboring only dimethyl-adenosine transferase 1 (TFB1M). The deletion breakpoints are flanked by bovine long interspersed nuclear elements Bov-B (upstream) and L1ME3 (downstream), suggesting a homologous recombination/deletion event." 2016 27128314

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 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.
Schütz, E., Wehrhahn, C., Wanjek, M., Bortfeld, R., Wemheuer, W.E., Beck, J., Brenig, B. :
The Holstein Friesian Lethal Haplotype 5 (HH5) Results from a Complete Deletion of TFB1M and Cholesterol Deficiency (CDH) from an ERV-(LTR) Insertion into the Coding Region of APOB. PLoS One 11:e0154602, 2016. Pubmed reference: 27128314. DOI: 10.1371/journal.pone.0154602.
Schütz, E., Wehrhahn, C., Wanjek, M., Bortfeld, R., Wemheuer, W.E., Beck, J., Brenig, B. :
Correction: The Holstein Friesian Lethal Haplotype 5 (HH5) Results from a Complete Deletion of TBF1M and Cholesterol Deficiency (CDH) from an ERV-(LTR) Insertion into the Coding Region of APOB. PLoS One 11:e0157618, 2016. Pubmed reference: 27280705. DOI: 10.1371/journal.pone.0157618.
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 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 Cooper, T.A., Wiggans, G.R., VanRaden, P.M., Hutchison, J.L., Cole, J.B., Null, D.J. :
Genomic evaluation of Ayrshire dairy cattle and new haplotypes affecting fertility and stillbirth in Holstein, Brown Swiss and Ayrshire breeds. ADSA-ASAS Joint Annual Meeting :poster T206, 2013.
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 02 May 2016
  • Changed by Frank Nicholas on 03 May 2016