OMIA 001931-9913 : Depigmentation associated with microphthalmia in Bos taurus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 193510 , 103500

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Molecular basis: Having access to tissue from just a single affected calf and its normal parents, and having noted the calf's resemblance to disorders in humans (see OMIM links above) and various animal species (including horse {OMIA 000214-9796, OMIA 001688-9796}, cattle {OMIA 000214-9913, OMIA 001680-9913, OMIA 001931-9913}, and dog {OMIA 000214-9615}) due to mutations in the MITF gene, Wiedemar and Drögemüller (2014) sequenced "all exons of the MITF gene in the calf, mother and father . . . to look for possible de novo mutations". Although no potential causal variants were detected, the authors did notice that "there were three intronic and four exonic SNPs for which the father showed homozygosity for one allele, the mother for the other allele and, surprisingly, the calf was not heterozygous in these SNPs as expected but carried the maternal alleles only", implying deletion of the paternal chromosome in the calf. Having verified correct parentage via the ISAG bovine parentage microsatellite panel, the authors genotyped the calf and its parents with the Illumina BovineHD BeadChip (777 962 SNPs), which revealed that of the 855 SNPs exhibiting non-Mendelian inheritance, 307 were located within a 17.2 Mb region of chromosome BTA22 containing the MITF gene, and for each of these markers, the calf had inherited only the maternal allele. Subsequent analysis of all BTA22 SNPs enabled Wiedemar and Drögemüller (2014) to conclude that this disorder is due to a de novo deletion of a 19.1 Mb region of BTA22 from 28 835 247–47 983 179 which "contains 132 annotated genes and loci" including MITF. It remains an open question as to whether the disorder is due solely to the deletion of MITF or to the deletion of some other genes as well.

Clinical features: As reported by Wiedemar and Drögemüller (2014), "the calf shows a complete absence of pigment, small eyes and musculoskeletal malformations affecting all four limbs. It seems not to be able to fully stretch its limbs and, in addition, it shows visible muscular atrophy."

Breed: Holstein.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MITF microphthalmia-associated transcription factor Bos taurus 22 NC_037349.1 (31843514..31614654) MITF Homologene, Ensembl, NCBI gene

Variants

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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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Holstein Depigmentation associated with microphthalmia MITF deletion, gross (>20) a de novo deletion of a 19.1 Mb region of BTA22 from 28 835 247-47 983 179 2014 25199536

Reference


2014 Wiedemar, N., Drögemüller, C. :
A 19-Mb de novo deletion on BTA 22 including MITF leads to microphthalmia and the absence of pigmentation in a Holstein calf. Anim Genet :, 2014. Pubmed reference: 25199536. DOI: 10.1111/age.12213.

Edit History


  • Created by Frank Nicholas on 22 Sep 2014
  • Changed by Frank Nicholas on 22 Sep 2014