OMIA:001952-9940 : Microtia in Ovis aries (sheep)
In other species: pig
Categories: Hearing / vestibular / ear phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2020
Species-specific description: Hereditary underdevelopment of the ear
Mapping: Having genotyped 8 affected and 12 non-affected sheep each with the Illumina OvineSNP50® chip, Jawasreh et al. (2016) reported that "a single-locus analysis revealed a statistically significant association (P = 0.012, genome-wide) with a SNP at basepair 34 647 499 on OAR23. This marker is adjacent to the gene encoding transcription factor GATA-6, which has been shown to play a role in many developmental processes, including chondrogenesis. The lack of extended homozygosity in this region suggests a fairly ancient mutation, and the time of occurrence was estimated to be approximately 3000 years ago."
Mastrangelo et al. (2018) obtained a strong signal on a different chromosome in the Valle del Belice breed: "A total of 40 individuals, 20 with microtia and 20 normal, were genotyped with the Illumina OvineSNP50 BeadChip. The comparison among the results from a genome-wide association study, Fisher's exact test and FST analysis revealed a single strong association signal: rs419889303 on chromosome 1, located within intron 3 of the CLRN1 gene. Our study suggests for the first time that this novel candidate gene is responsible for microtia in sheep."
In the Altay breed, a GWAS by He et al. (2020) identified a region on chromosome OAR6.
Molecular basis: Within the candidate region on chromosome OAR6, He et al. (2020) identified a 76-bp duplication in the HMX1 gene that was completely concordant with microtia in their sample of 129 Altay sheep, and is absent from 6 other breeds investigated.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Awassi (Sheep) (VBO_0001308).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|HMX1||H6 family homeobox 1||Ovis aries||6||NC_056059.1 (115750422..115745800)||HMX1||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|
|1153||Altay Fat-Rumped, China (Sheep)||Microtia||HMX1||duplication||Naturally occurring variant||Oar_rambouillet_v1.0||6||He et al. (2020): "a 76 bp duplication of HMX1" (duplication of 76bp segment 6:126893417-126893492)||2020||31691317|
Cite this entry
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.
|2020||He, S., Zhang, Z., Sun, Y., Ren, T., Li, W., Zhou, X., Michal, J.J., Jiang, Z., Liu, M. :|
|Genome-wide association study shows that microtia in Altay sheep is caused by a 76 bp duplication of HMX1. Anim Genet 51:132-136, 2020. Pubmed reference: 31691317. DOI: 10.1111/age.12876.|
|2018||Mastrangelo, S., Sottile, G., Sutera, A.M., Di Gerlando, R., Tolone, M., Moscarelli, A., Sardina, M.T., Portolano, B. :|
|Genome-wide association study reveals the locus responsible for microtia in Valle del Belice sheep breed. Anim Genet 49:636-640, 2018. Pubmed reference: 30160299. DOI: 10.1111/age.12719.|
|2016||Jawasreh, K., Boettcher, P.J., Stella, A. :|
|Genome-wide association scan suggests basis for microtia in Awassi sheep. Anim Genet 47:504-6, 2016. Pubmed reference: 26990958. DOI: 10.1111/age.12431.|
|2002||Porter, V. :|
|Mason's World Dictionary of Livestock Breeds, Types and Varieties. 5th edn. C.A.B International, Wallingford, UK. , 2002.|
|1930||Lush, J.L. :|
|Earlessness in Karakul sheep Journal of Heredity 21:107-112, 1930.|
- Created by Frank Nicholas on 26 Mar 2016
- Changed by Frank Nicholas on 03 Sep 2018
- Changed by Frank Nicholas on 31 Jan 2020