OMIA:000031-9913 : Coat colour, dilution, MLPH-related in Bos taurus
In other species: dog , domestic cat , rabbit , American mink , sheep
Categories: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 609227 (trait) , 606526 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2015
Cross-species summary: FN acknowledges invaluable feedback from Cord Drögemüller that has led to the name of this phene being changed from "Coat colour, diluted" to "Coat colour, dilution, MLPH-related". At the same time, a new phene "Coat colour, dilution, generic" was created.
Species-specific name: Cool gray; Larson Blue
Species-specific description: In a reversal of the normal sequence of discovery, Li et al. (2016) discovered this phenotype AFTER identifying the causal mutation, by noticing that all Belgian Blue cattle with a particular mutation (MLPH: c.87_96del; p.Glu32Aspfs*1), which inactivates MLPH, have an expected dilution phenotype which the authors called "cool gray".
History: Dikmen et al. (2017) reported "a previously undescribed coat color phenotype in Holstein cattle. Larson Blue Holsteins, located on a dairy in south Florida, exhibit a coloration pattern that is similar to that of black and white or red and white Holsteins except that, instead of being black or red, darker regions of the body vary in color from gray to taupe. The Larson Blue phenotype was readily apparent in young calves."
Molecular basis: As reported by Li et al. (2016) [published online in 2015], "In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein." Belgian Blue cattle homozygous for this mutant (and with the appropriate genotype at the epistatic KIT locus) all exhibited a dilution coat colour phenotype (as expected with a mutation that inactivates MLPH), which the authors called "cool gray".
Having shown that the Larson Blue "phenotype is not due to inheritance of known mutations causing coat color variation in cattle, including dominant red, Telstar, silver color dilutor, or Dun color", Dikmen et al. (2017) whole-genome sequenced two Larson Blue cows and identified "Three variants with moderate effects on the melanophilin (MLPH) gene were identified in 2 Larson blue cows" but noted that "tools for prediction of the simultaneous effect of 3 missense mutations on the MLPH protein are not available, so additional research is needed to confirm the effect of these AA changes on MLPH function. It is also not known whether the variants identified in MLPH exist in wild-type cows in the Larson herd."
Prevalence: Li et al. (2016) reported a 5% frequency of the p.Glu32Aspfs*1 allele in Belgian Blue cattle.
Breed: Belgian Blue (Cattle) (VBO_0000139).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MLPH||melanophilin||Bos taurus||3||NC_037330.1 (116959514..117005443)||MLPH||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|
|553||Belgian Blue (Cattle)||Coat colour, cool gray||MLPH||deletion, small (<=20)||Naturally occurring variant||ARS-UCD1.2||3||g.116966611_116966620del||c.87_96del||p.(E32Dfs*1)||2016||26582259||The genomic location on ARS-UCD1.2 was determined by Katie Eager & Shernae Woolley, EMAI, NSW Department of Primary Industries.|
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.
|2017||Dikmen, S., Dahl, G.E., Cole, J.B., Null, D.J., Hansen, P.J. :|
|The Larson Blue coat color phenotype in Holsteins: Characteristics and effects on body temperature regulation and production in lactating cows in a hot climate. J Anim Sci 95:1164-1169, 2017. Pubmed reference: 28380539 . DOI: 10.2527/jas.2016.1148.|
|2016||Li, W., Sartelet, A., Tamma, N., Coppieters, W., Georges, M., Charlier, C. :|
|Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle. Anim Genet 47:110-3, 2016. Pubmed reference: 26582259 . DOI: 10.1111/age.12383.|
- Changed by Frank Nicholas on 13 Sep 2018
- Created by Frank Nicholas on 13 Sep 2018
- Changed by Frank Nicholas on 02 Mar 2020