Categories: Mortality / aging (incl. embryonic lethal)

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 611237 (gene) , 603337 (gene) , 138750 (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

Species-specific description: Stillbirth occurs in many different forms, many of which are not inherited, some are multifactorial and others are single locus disorders.

Mapping: From a GWAS on 4.631 Nordic Red bulls, Sahana et al. (2016) identified a QTL for birth index on chromosome BTA23. Further research indicated a deletion of approximately 500kb in the region 12.28Mb and 12.81Mb on BTA23, acting as an autosomal recessive lethal for still births. As reported by Sahana et al. (2016), three genes (BTBD9, GLO1 and DNAH8) are known to be located in the deleted region, but it was not evident why lack of any of these genes would result in still births.

Mesbah-Uddin et al. (2017) "identified and confirmed the breakpoint of [the above] ∼525 KB deletion on Chr23:12,291,761-12,817,087 (overlapping BTBD9, GLO1 and DNAH8)".

Fonseca et al. (2022) identified “candidate genomic regions associated with stillbirth using a haplotype library and a repeated measures model and …[prioretized] potential functional candidate genes associated with biological processes associated with stillbirth in dairy cattle. … 10,570 cows and 50,541 birth records were used to perform a haplotype-based GWAS. A total of 41 significantly associated pseudo-SNPs (haplotypes within haplotype blocks converted to a binary classification) were identified after Bonferroni adjustment for multiple tests. A total of 117 positional candidate genes were annotated within or close (in a 200-kb interval) to significant pseudo-SNPs (haplotype blocks). The guilt-by-association functional prioritization identified 31 potential functional candidate genes for reproductive performance …”

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Prevalence: Wu et al. (2020) reported the frequency of a tag haplotype for this lethal effect as 4.1% in 19,309 Nordic Red Dairy cattle.

Breed: 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

Associated genes: