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: