Association of Melanophilin (MLPH) gene polymorphism with coat colour in Rex rabbits

J. Li, Y. Chen, M. Liu, Q. Chen, J. Zhou, G. Bao, X. Wu
DOI: https://doi.org/10.4995/wrs.2020.12082

Abstract

Rex rabbit, with multiple phenotypes and colourful fur, is an interesting model for assessing the effect of coat colour gene mutations on characteristic pigmentation phenotype. Based on previous study, the melanophilin (MLPH) gene is a positional candidate gene related coat colour dilution. The fur colours are a lighter shade, e.g. grey instead of black. We sequenced 1689 base pairs of the MLPH gene in Chinchilla and black Rex rabbit. A total of 13 polymorphisms were identified, including seven missense mutations. The rabbit MLPH gene has a very high GC content and the protein shows 64.87% identity to the orthologous human protein (lack of homologous amino acids encoded by human MLPH exon 9). Hardy-Weinberg test showed that, except for the g.606C>A single nucleotid polymorphism (SNP), all other SNPs were in Hardy-Weinberg equilibrium. Haplotype analysis revealed that the seven missense mutation SNPs of two strains of Rex rabbits formed 10 haplotypes, but there were only seven major types of haplotypes (haplotype frequency P>0.05). The major haplotypes of the Chinchilla and black Rex rabbits were H1/H2/H3/H4/H5 and H1/H2/H3/H6/H8, respectively. The special haplotypes of Chinchilla Rex rabbit (H4, H5, H7) were consistently associated with the Chinchilla phenotype. This study provides evidence that different coat colour formation may be caused by one or more mutations within MLPH gene in several Rex rabbit strains. The data on polymorphisms that are associated with the Chinchilla phenotype facilitate the breeding of rabbits with defined coat colours.

Keywords

MLPH; Rex rabbit; polymorphism; coat colour

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References

Ardlie K.G., Kruglyak L., Seielstad M. 2002. Patterns of linkage disequilibrium in the human genome. Nature Reviews Genetics, 3: 299-309. https://doi.org/10.1038/nrg777

Barral D.C., Seabra M.C. 2004. The Melanosome as a Model to Study Organelle Motility in Mammals. Pigment Cell Res., 17: 111-118. https://doi.org/10.1111/j.1600-0749.2004.00138.x

Bauer A., Kehl A., Jagannathan V., Leeb T. 2018. A novel MLPH variant in dogs with coat colour dilution. Animal Genet., 49: 94-97. https://doi.org/10.1111/age.12632

Bennett D.C., Lamoreux M.L. 2003. The Colour Loci of Mice - A Genetic Century. Pigm. Cell Res., 16: 333-344. https://doi.org/10.1034/j.1600-0749.2003.00067.x

Cao Q.J., Zhang N., Zhou R., Yao L.L., Li X.D. 2019. The cargo adaptor proteins RILPL2 and melanophilin co-regulate myosin-5a motor activity. J. Biol. Chem., 294: 11333-11341. https://doi.org/10.1074/jbc.RA119.007384

Choudhury B. 1987. Visual cortex in the albino rabbit. Exp.Brain Res., 66: 565-571. https://doi.org/10.1007/BF00270689

Cirera S., Markakis M.N., Christensen K., Anistoroaei R. 2013. New insights into the melanophilin (MLPH ) gene controlling coat colour phenotypes in American mink. Gene, 527: 48-54. https://doi.org/10.1016/j.gene.2013.05.047

Eiberg H., Mohr J. 1996. Assignment of genes coding for brown eye colour (BEY2) and brown hair colour (HCL3) on chromosome 15q. Eur. J. Human Gen., 4: 237-241. https://doi.org/10.1159/000472205

Fontanesi L., Scotti E., Allain D., Dall'Olio S. 2014. A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds. Animal Genet., 45: 248-255. https://doi.org/10.1111/age.12104

Fontanesi L., Scotti E., Dall'Olio S., Oulmouden A., Russo V. 2012. 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 Sci., 20: 35-41. https://doi.org/10.4995/wrs.2012.1033

Fukuda M., Kuroda T.S., Mikoshiba K. 2002. Slac2-a/melanophilin, the missing link between Rab27 and myosin Va - Implications of a tripartite protein complex for melanosome transport. J. Biol. Chem., 277: 12432-12436. https://doi.org/10.1074/jbc.C200005200

Hume A.N., Tarafder A.K., Ramalho J.S., Sviderskaya E.V., Seabra M.C. 2006. A Coiled-Coil Domain of Melanophilin Is Essential for Myosin Va Recruitment and Melanosome Transport in Melanocytes. Mol. Biol. Cell, 17: 4720-4735. https://doi.org/10.1091/mbc.e06-05-0457

Ishida Y., David V.A., Eizirik E., Schäffer A.A., Neelam B.A., Roelke M.E., Hannah S.S., O'Brien S.J., Menotti-Raymond M. 2006. A homozygous single-base deletion in MLPH causes the dilute coat colour phenotype in the domestic cat. Genomics, 88: 698-705. https://doi.org/10.1016/j.ygeno.2006.06.006

Krawczak M., Reiss J., Cooper D.N. 1992. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet., 90: 41-54. https://doi.org/10.1007/BF00210743

Lehner S., Gähle M., Dierks C., Stelter R., Gerber J., Brehm R., Distl O. 2013. Two-Exon Skipping within MLPH Is Associated with Coat Colour Dilution in Rabbits. Plos One, 8: e84525. https://doi.org/10.1371/journal.pone.0084525

Li X.D., Ikebe R., Ikebe M. 2005. Activation of Myosin Va Function by Melanophilin, a Specific Docking Partner of Myosin Va. J. Biol. Chem., 280: 17815-17822. https://doi.org/10.1074/jbc.M413295200

Matesic L.E., Yip R., Reuss A.E., Swing D.A., O'Sullivan T.N., Fletcher C.F., Copeland N.G., Jenkins N.A. 2001. Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice. In Proc: National Academy of Sciences of the United States of America, 98: 10238-10243. https://doi.org/10.1073/pnas.181336698

Ménasché G., Chen H.H., Sanal O., Feldmann J., Basile G.D.S. 2003. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J. Clin. Invest., 112: 450-456. https://doi.org/10.1172/JCI200318264

Mengel-From J., Wong T.H., Morling N., Rees J.L., Jackson I.J. 2009. Genetic determinants of hair and eye colours in the Scottish and Danish populations. BMC Genet., 10: 88. https://doi.org/10.1186/1471-2156-10-88

Mercer J.A., Seperack P.K., Strobel M.C., Copeland N.G., Jenkins N.A. 1991. Novel myosin heavy chain encoded by murine dilute coat colour locus. Nature, 349: 709-713. https://doi.org/10.1038/349709a0

Nagashima K., Torii S., Yi Z., Igarashi M., Okamoto K., Takeuchi T., Izumi T. 2002. Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions. FEBS Lett., 517: 0-238. https://doi.org/10.1016/S0014-5793(02)02634-0

Philipp U., Hamann H., Mecklenburg L., Nishino S., Mignot E., Günzelapel A.R., Schmutz S.M., Leeb T. 2005. Polymorphisms within the canine MLPH gene are associated with dilute coat colour in dogs. BMC Genet., 6: 34. https://doi.org/10.1186/1471-2156-6-34

Reed R. 1989. The organization of 3' splice-site sequences in mammalian introns. Gene. Dev., 3: 2113-2123. https://doi.org/10.1101/gad.3.12b.2113

Roscigno R.F., Weiner M., Garcia-Blanco M.A. 1993. A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing. J. Biol. Chem., 268: 11222-11229.

Sckolnick M., Krementsova E.B., Warshaw D.M., Trybus K.M. 2013. More Than Just a Cargo Adapter, Melanophilin Prolongs and Slows Processive Runs of Myosin Va. J. Biol. Chem., 288: 29313-29322. https://doi.org/10.1074/jbc.M113.476929

Shifman S., Kuypers J., Kokoris M., Yakir B., Darvasi A. 2003. Linkage disequilibrium patterns of the human genome across populations. Hum. Mol. Genet., 12: 771-776. https://doi.org/10.1093/hmg/ddg088

Strom, M. 2002. A Family of Rab27-binding Proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport. J. Biol. Chem., 277: 25423-25430. https://doi.org/10.1074/jbc.M202574200

Wilson S.M., Yip R., Swing D.A., O'Sullivan T.N., Zhang Y., Novak E.K., Swank R.T., Russell L.B., Copeland N.G., Jenkinks N.A. 2000. A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. In Proc.: National Academy of Sciences of the United States of America, 97: 7933-7938. https://doi.org/10.1073/pnas.140212797

Wu X.S., Rao K., Zhang H., Wang F., Sellers J.R., Matesic L.E., Copeland N.G., Jenkins N.A., Hammer J.A. 2002. Identification of an organelle receptor for myosin-Va. Nature Cell Biol., 4: 271-278. https://doi.org/10.1038/ncb760

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