Categories: Mortality / aging (incl. embryonic lethal)

Mendelian trait/disorder: unknown

Disease-related: yes

Species-specific name: HH3 HH5 HH13 HH18 HH19 HH20 HH21 HH22 HH23 HH24 HH25 HH26 HH27 HH28 HH29 HH30 HH31 HH32 HH33 HH34 HH35 HH36 HH37 HH38

Species-specific description: Häfliger et al. (2022) "performed haplotype screenings on almost 53 thousand genotyped [Holstein] animals including 114 k SNP data with two different approaches. We revealed significant haplotype associations to several survival, birth and fertility traits. Within haplotype regions, we mined WGS data of hundreds of bovine genomes for candidate causal variants, which were subsequently evaluated by using a custom genotyping array in several thousand breeding animals. With this approach, we confirmed the known deleterious SMC2:p.Phe1135Ser missense variant associated with Holstein haplotype (HH) 3 [see OMIA 001824-9913]. For ... previously reported deficient homozygous haplotypes that show negative associations to female fertility traits, we propose candidate causative loss-of-function .. [variant]: the HH13-related KIR2DS1:p.Gln159* nonsense variant [see OMIA 001836-9913] ... . In addition, we propose the RIOX1:p.Ala133_Glu142del deletion [see OMIA 002547-9913] as well as the PCDH15:p.Leu867Val missense variant [see OMIA 002548-9913] to explain the unexpected low number of homozygous haplotype carriers for HH25 and HH35, respectively."

Mapping: Häfliger et al. (2022) identified several haplotypes with homozygous deficiency, some of these had been previously reported. Likely causal variants have been confirmed for haplotype HH3 and identified for haplotypes HH13, 25 and 35 (see haplptype specific OMIA entries for these haplotypes). A reported variant in the NOTCH3 gene was later identified to not be causal for HH21 (Cord Drögemüller, pers. communication). Detail of chromosomal location of all identified haplotypes are listed below: Name chr:Pos in Mb in ARS-UCD1.2 (Comment) HH3 8:90.959–92.085 (see OMIA 001824-9913, haplotype previously described) HH5 9:90.928–91.824 (haplotype previously described) HH13 18:60.932–62.101 and 62.070–63.045 (see OMIA 001836-9913, haplotype previously described) HH18 1:10.302–104.376 HH19 1:139.874–140.643 (haplotype co-localises with previously described haplotype) HH20 2:134.477–135.148 HH21 7:7.872–10.433 (haplotype previously described, reported NOTCH3 variant is not causal) HH22 7:93.582–94.642 HH23 8:15.562–16.863 HH24 8:66.699–68.006 HH25 10:86.876–87.773 (see OMIA 002547-9913) HH26 11:4.531–5.362 HH27 13:7.083–8.297 HH28 14:24.591–24.827 HH29 14:58.128–59.238 HH30 21:7.844–8.671 HH31 22:59.811–60.704 HH32 23:32.773–33.726 and 33.545–34.948 HH33 24:44.693–45.678 HH34 25:36.162–37.330 HH35 26:3.359–4.235 (see OMIA 002548-9913) HH36 28:28.541–29.736 and 29.731–30.877 HH37 28:40.348–41.271 HH38 29:14.243–15.317

Breed: Holstein Friesian (Cattle) (VBO_0000239).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).