OMIA:000031-9986 : Coat colour, dilution, MLPH-related in Oryctolagus cuniculus (rabbit)
Categories: Pigmentation phene
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: 2013
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.
Molecular basis: By sequencing the MLPH gene in two dilute and one black rabbits, Lehner et al. (2013) discovered a "c.111-5C>A splice acceptor mutation within the polypyrimidine tract of intron 2", resulting in "p.QGL[37-39]QWA and a premature stop codon at p.K40*" as being a likely causal mutation for dilute. They also reported another likely causal mutation, namely a "frame shift mutation within exon 6 (c.585delG)"
Adopting a comparative candidate gene strategy, Fontanesi et al. (2014) sequenced the rabbit MLPH gene and identified the same likely causal mutation mentioned by Lehner et al. (2013), namely "a deletion of one nucleotide in exon 5 (g.549853delG) that causes a shift in the reading frame that determines a completely different protein from the beginning of this exon . . . until the second half of exon 8 in which a stop codon would be introduced".
By comparing the segregation of both variants with coat colour in 73 animals from two breeds, Demars et al. (2018) showed that only the deletion variant segregated perfectly with coat colour. Combining these results with other evidence, Demars et al. (2018) concluded that "The c.585delG variant remains as the most likely causative variant for coat color dilution in multiple rabbit breeds."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Netherland dwarf (Rabbit) (VBO_0001266).
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|
|MLPH||melanophilin||Oryctolagus cuniculus||NW_026259270.1 (743904..707632)||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|
|932||Lionhead Dwarf Loh Netherland dwarf (Rabbit)||Coat colour, dilute||MLPH||deletion, small (<=20)||Naturally occurring variant||OryCun2.0||NW_003159466.1||g.549853del||c.586del||p.(E196fs)||NM_001297485.1; NP_001284414.1; published as g.549853delG, c.585delG, p.(L195Lfs*123) - information in this table has been updated to reflect HGVS nomenclature recommendations||2013||24376820|
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.
|2021||Dorożyńska, K., Maj, D. :|
|Rabbits - their domestication and molecular genetics of hair coat development and quality. Anim Genet 52:10-20, 2021. Pubmed reference: 33216407. DOI: 10.1111/age.13024.|
|Jia, X., Ding, P., Chen, S., Zhao, S., Wang, J., Lai, S. :|
|Analysis of MC1R, MITF, TYR, TYRP1, and MLPH genes polymorphism in four rabbit breeds with different coat colors. Animals (Basel) 11, 2021. Pubmed reference: 33466315. DOI: 10.3390/ani11010081.|
|2020||Li, J., Chen, Y., Liu, M., Chen, Q., Wu, X. :|
|Association of melanophilin (MLPH) gene polymorphism with coat colour in Rex rabbits World Rabbit Sci 28:29, 2020. DOI: doi: 10.4995/wrs.2020.12082.|
|2018||Demars, J., Iannuccelli, N., Utzeri, V.J., Auvinet, G., Riquet, J., Fontanesi, L., Allain, D. :|
|New insights into the Melanophilin MLPH) Gene Affecting Coat Color Dilution in Rabbits. Genes (Basel) 9, 2018. Pubmed reference: 30142960. DOI: 10.3390/genes9090430.|
|2014||Fontanesi, L., Scotti, E., Allain, D., Dall'olio, S. :|
|A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds. Anim Genet 45:248-55, 2014. Pubmed reference: 24320228. DOI: 10.1111/age.12104.|
|2013||Lehner, S., Gähle, M., Dierks, C., Stelter, R., Gerber, J., Brehm, R., Distl, O. :|
|Two-exon skipping within MLPH is associated with coat color dilution in rabbits. PLoS One 8:e84525, 2013. Pubmed reference: 24376820. DOI: 10.1371/journal.pone.0084525.|
|2012||Fontanesi, L., Scotti, E., Dall'Olio, S., Oulmouden, A., Russo, V. :|
|Identification and analysis of single nucleotide polymorphisms in the myosin VA (MYO5A) gene and its exclusion as the causative gene of the dilute coat colour locus in rabbit. World Rabbit Science 20:35-41, 2012.|
|1958||Robinson, R. :|
|Genetic studies of the rabbit. Bibliographia Genetica 17:229–558, 1958.|
|1909||Castle, W.E., Walter, H.E., Mullenix, R.C., Cobb, S. :|
|Studies of Inheritance in Rabbits. Carnegie Institute Washington Publication, Washington. series no. 114 , 1909.|
- Created by Frank Nicholas on 15 Sep 2018
- Changed by Imke Tammen2 on 09 Apr 2021
- Changed by Imke Tammen2 on 06 Mar 2023