Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 193510 (trait) , 103500 (trait) , 156845 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: 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 (black and white) (Cattle) (VBO_0000237).
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).

Associated gene: