In other species: pig

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 200110 (trait) , 209885 (trait) , 227260 (trait) , 607556 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: no

Key variant known: yes

Year key variant first reported: 2017

Species-specific name: Belted

History: As reported by Awasthi Mishra et al. (2017): "A 15th century painting from Austria already depicts a belted ox suggesting that this allele is at least 600 years or roughly 200 generations old (S1 Fig). Historic records are in agreement with a central European origin of the bt allele and indicate that the bt allele may subsequently have spread north-west and been introgressed into Dutch cattle to eventually form the Dutch Belted cattle and into Scottish cattle to eventually form the Belted Galloways"

Mapping: Drögemüller et al. (2009) mapped this locus in Brown Swiss cattle to a 922 kb region on chromosome BTA3. In a second paper in the same year, the authors reported narrowing down the candidate region to 336 kb. No compelling functional candidate gene could be identified in the interval.

Molecular basis: Awasthi Mishra et al. (2017) reported a likely causal variant for this classic phene: "The belt-associated variant was a copy number variant (CNV) involving the quadruplication of a 6 kb non-coding sequence located approximately 16 kb upstream of the TWIST2 gene. Increased copy numbers at this CNV were strongly associated with the belt phenotype in a cohort of 333 cases and 1322 controls. We hypothesized that the CNV causes aberrant expression of TWIST2 during neural crest development, which might negatively affect melanoblasts. Functional studies showed that ectopic expression of bovine TWIST2 in neural crest in transgenic zebrafish led to a decrease in melanocyte numbers." In the first reported use of long-read (Oxford Nanopore) sequencing for investigating a single-locus trait in domestic animals, Rothammer et al. (2018) confirmed the quadruplication variant reported by Awasthi Mishra et al. (2017), and extended the number of breeds in which this variant occurs.

Prevalence: A survey of 333 belted cattle from three belted breeds (Brown Swiss, Belted Galloway and Lakenvelder) and 1322 non-belted cattle by Awasthi Mishra et al. (2017) showed that "copy numbers varied between 2 and 12 with the most frequently observed values being 2, 5 and 8, which most likely corresponded to the copy number genotypes 1/1, 1/4, and 4/4. The belt phenotype was strongly associated with an increased copy number at the CNV . . . . The copy number was not associated with the width, position, or regularity of the belt."

Breeds: Belted Galloway (Cattle) (VBO_0000142), Brown Swiss (Cattle) (VBO_0000166), Dutch Belted (Cattle) (VBO_0000197), Lakenvelder (Cattle) (VBO_0000267), Yakutskii Skot, Russian Federation (Cattle) (VBO_0004351).
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: