OMIA 002505-9913 : Haplotype with homozygous deficiency SH5, DIS3-related in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 607533 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific description: Häfliger et al. (2021) “report the result of a large-scale reverse genetic screen in the Swiss Simmental population …. We used 115,000 phased SNP data of almost 10 thousand cattle with pedigree data. This revealed evidence for 11 genomic regions … with haplotypes (SH1 to SH11) showing a significant depletion in homozygosity and an allele frequency between 3.2 and 10.6%. For the proposed haplotypes, it was unfortunately not possible to evaluate associations with fertility traits as no corresponding data were available. …. Subsequent mining of single-nucleotide variants and short indels in the genomes of 23 sequenced haplotype carriers allowed us to identify three perfectly linked candidate causative protein-changing variants … [for haplotypes SH5, SH8 and SH9]. … Four selected haplotypes (SH5, SH7, SH8, and SH10) presented a complete deficit of observed homozygous animals, whereas the others showed a partial deficiency ranging from 85 to 96% of the expected homozygotes….”

Mapping: Häfliger et al. (2021): “Due to the application of several routinely available SNP arrays ranging from 9000 to 150,000 SNPs, the [genotyping] data had to be imputed …. haplotypes showing a deviation from the HWE, indicated by depletion of homozygosity, were identified. The first subset of data analyzed included only fully genotyped trios where the complete trio (sire, dam, and offspring) were genotyped (n = 2626), further called “trio” approach. The second dataset analyzed included genotyped trios where an offspring and two paternal animals (sire and maternal grandfather) were genotyped (n = 3969), subsequently called parent–grandparent “pgp” approach.”

The SH5 haplotype was mapped to ARS-UCD1.2 Chr12:46.828–47.837 MB using the trio approach and Chr:12: 46.831–47.843 MB using the pgp approach (depletion of homozygosity =100%, allele frequency = 0.062).

Molecular basis: Häfliger et al. (2021): “With the selected haplotypes, we predicted individual diplotypes that represent if an animal carries one, two, or no copies of the haplotype. Based on these diplotypes, we selected three carrier animals for whole-genome sequencing (WGS) for each haplotype region. … For three deficient homozygous haplotypes (SH5, SH8, and SH9), by linkage disequilibrium analysis, we found perfectly linked (r2 = 1) candidate causal variants. … None of these variants occurred in homozygous state in any of more than 5200 sequenced cattle of various breeds. Selection against these alleles in order to reduce reproductive failure and animal loss is recommended.”

SH5: DIS3 c.2032dupA, p.Ile678AsnTer2 (XM_025000110.1)

Breed: Simmental.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
DIS3 DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease Bos taurus 12 NC_037339.1 (47532768..47504541) DIS3 Homologene, Ensembl, NCBI gene


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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.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1412 Simmental Haplotype with homozygous deficiency SH5 DIS3 SH5 insertion, small (<=20) Naturally occurring variant ARS-UCD1.2 12 g.47511687_47511687insT c.2032dup p.(I678N*2) NP_025000110.1, XM_025000110.1 2021 34944310


2021 Häfliger, I.M., Seefried, F.R., Drögemüller, C. :
Reverse genetic screen for deleterious recessive variants in the local Simmental cattle population of Switzerland. Animals (Basel) 11:3535, 2021. Pubmed reference: 34944310. DOI: 10.3390/ani11123535.

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  • Created by Imke Tammen2 on 13 Jan 2022