OMIA 000209-9823 : Coat colour, dominant white in Sus scrofa

In other species: rabbit , cattle , dog , horse , domestic cat , llama , alpaca , Arctic fox , ass , raccoon dog

Possibly relevant human trait(s) and/or gene(s) (MIM number): 172800

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 1996

Cross-species summary: The dominant white gene is one of a number of genes that regulate normal growth and proliferation of cells. In fact, it encodes a protein that protrudes through the cell membrane, relaying 'messages' across the membrane, from outside to inside the cell. The transmembrane domain of the protein is a receptor for a growth factor (a protein produced by one type of cell, that acts on another type of cell). The domain inside the cell has tyrosine kinase activity. When a growth factor binds to the receptor on the outside of the cell, this stimulates tyrosine kinase activity inside the cell, which sets off a cascade of phosphorylations, resulting in activation of transcription factors, which in turn activate genes, resulting in multiplication of stem cells, including melanocyte precursor cells, in the developing embryo. This whole process is known as a signal transduction pathway. During embryonic development, the melanosome precursor cells migrate from the neural crest down either side of the body. Under normal circumstances, they eventually meet at the centre of the belly. The cells then proliferate in all directions until they meeting neighbouring cells, thereby filling up all available areas, resulting in a solid mass of melanocytes over the entire body. The dominant white allele produces a defective transmembrane protein which is unable to relay 'messages', resulting in a lack of melanocytes, and hence white coat colour. An interesting aspect of the dominant white gene is that if it is activated at the wrong time, the result can be excess and uncontrolled proliferation of stem cells; in other words, cancer. In fact, at some time in the past, a feline retrovirus (the Hardy-Zuckerman 4 feline sarcoma virus) 'picked up' (by transduction) a copy of the dominant white gene from a cat, and incorporated this gene into its own genome. When this retrovirus infects cats, it activates its own copy of the gene at inappropriate times, causing sarcoma - a malignant tumour of cells derived from connective tissue. Retroviral genes that cause cancer are called oncogenes. The original host version of an oncogene is called a proto-oncogene. Thus, the dominant white gene is actually a proto-oncogene. In this particular case, the oncogene was discovered and named v-kit (where 'v' indicates a viral version of the gene) long before its association with white coat colour was established. The corresponding proto-oncogene is called c-kit, where 'c' stands for cellular. After the discovery and cloning of v-kit in the feline retrovirus by Besmer et al. (1986; Nature 320:415-421), c-kit was identified and mapped first in humans, by Mattei et al. (1987; Cytogenetics and Cell Genetics 46:657 only), and then in mice (Chabot et al., 1988; Nature 335:88-89, 1988), where it was shown to be identical with the long-recognised white-spotting (W) locus. Three years later, Giebel and Spritz (1991; Proceedings of the National Academy of Sciences 88:8696-8699) showed that mutations at the c-kit gene in humans cause piebaldism, which is the human homologue of white spotting (see the MIM entry at the top of this page)

Inheritance: The dominant autosomal inheritance of white coats in pigs was determined soon after the re-discovery of Mendelism, by Spillman (1906). The results of Rubin et al. (2012) indicate four alleles at this locus, namely Wild-type, Dominant white (this entry), Patch (OMIA 001743-9825) and Belt (OMIA 001745-9825). (with thanks to Leif Andersson)

Mapping: In 1992, Johansson et al. showed that the porcine dominant white locus (designated I) is located on pig chromosome SSC8, in a region homologous with the region of mouse chromosome 5 that contains three white-spotting genes, including the c-kit proto-oncogene, which is the gene for dominant white spotting (W) in the mouse. This gene encodes the mast/stem cell growth factor receptor (MGFR). This result of Johansson et al. (1992) immediately suggested KIT as a very likely comparative positional candidate gene for dominant white spotting in pigs.

Molecular basis: In another excellent example of the power of comparative mapping (similar to the case of malignant hyperthermia in pigs), Johansson Moller et al. (1996) investigated the porcine KIT gene as a comparative positional candidate gene for dominant white spotting (based on the mapping results of Johansson et al. (1992) described above). Johansson Moller et al. (1996) were able to show that KIT is, indeed, the gene for dominant white in pigs: the white allele contains a duplication of part or all of the KIT gene, and this duplication results in a lack of melanocytes in the skin. In 1998, Marklund et al reported the molecular details of variants at this locus: the fully dominant white allele results from a splice mutation (a substitution of A for G in the first nucleotide of intron 17, resulting in the loss of exon 17), which is presumed to give rise to a MGFR with impaired or absent tyrosine kinase activity. Another white allele, which is only partially dominant, results from a duplication of the KIT gene, which presumably affects gene expression.

Following analysis of whole-genome resequencing data from tens of pigs from a wide range of breeds, Rubin et al. (2012) have enhanced our understanding of this intriguing locus: the Dominant white allele carries at least three causal polymorphisms, namely a 450 kb duplication (also present in Patch - see OMIA 001743-9825), the splice mutation mentioned above (unique to Dominant white) and smaller duplication(s) (that occur within the 450kb duplication) causing Belt (see OMIA 001745-9825).(with thanks to Leif Andersson)

Genetic testing: Li et al. (2018) reported "a simple, rapid method, with high specificity and stability, for the detection of the KIT genotype in pigs was established using TaqMan MGB probe real-time quantitative PCR."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Sus scrofa 8 NC_010450.4 (41402334..41492306) KIT Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Dominant white KIT splicing a substitution of A for G in the first nucleotide of intron 17, resulting in the loss of exon 17 1998 9724328
Dominant white KIT complex rearrangement This dominant white allele carries at least three causal polymorphisms, namely a 450 kb duplication (also present in Patch - see OMIA 001743-9825), the splice mutation reported by Marklund et al. (1998) (unique to Dominant white) and smaller duplication(s) (that occur within the 450kb duplication) causing Belt (see OMIA 001745-9825).(with thanks to Leif Andersson) 2012 23151514

References


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.
2019 Qin, K., Liang, X., Sun, G., Shi, X., Wang, M., Liu, H., Chen, Y., Liu, X., He, Z. :
Highly efficient correction of structural mutations of 450 kb KIT locus in kidney cells of Yorkshire pig by CRISPR/Cas9. BMC Mol Cell Biol 20:4, 2019. Pubmed reference: 31041890. DOI: 10.1186/s12860-019-0184-5.
Wu, Z., Deng, Z., Huang, M., Hou, Y., Zhang, H., Chen, H., Ren, J. :
Whole-Genome Resequencing Identifies <i>KIT</i> New Alleles That Affect Coat Color Phenotypes in Pigs. Front Genet 10:218, 2019. Pubmed reference: 30949195. DOI: 10.3389/fgene.2019.00218.
2018 Li, X., Li, X., Luo, R., Wang, W., Wang, T., Tang, H. :
Detection of KIT Genotype in Pigs by TaqMan MGB Real-Time Quantitative PCR. DNA Cell Biol :, 2018. Pubmed reference: 29485917. DOI: 10.1089/dna.2017.4070.
Niu, L., Shi, K., Xie, J.J., Liu, S., Zhong, T. :
KIT Gene in European and Asian Domestic Pig Breeds. Biomed Res Int 2018:8932945, 2018. Pubmed reference: 30211229. DOI: 10.1155/2018/8932945.
2012 Rubin, C.J., Megens, H.J., Barrio, A.M., Maqbool, K., Sayyab, S., Schwochow, D., Wang, C., Carlborg, O., Jern, P., Jørgensen, C.B., Archibald, A.L., Fredholm, M., Groenen, M.A., Andersson, L. :
Strong signatures of selection in the domestic pig genome. Proc Natl Acad Sci U S A :, 2012. Pubmed reference: 23151514. DOI: 10.1073/pnas.1217149109.
2009 Andersson, L. :
Studying phenotypic evolution in domestic animals: a walk in the footsteps of Charles Darwin. Cold Spring Harb Symp Quant Biol 74:319-25, 2009. Pubmed reference: 20375320. DOI: 10.1101/sqb.2009.74.039.
2007 Lai, F., Ren, J., Ai, H., Ding, N., Ma, J., Zeng, D., Chen, C., Guo, Y., Huang, L. :
Chinese White Rongchang Pig Does Not Have the Dominant White Allele of KIT but Has the Dominant Black Allele of MC1R. J Hered 98:84-87, 2007. Pubmed reference: 17150979. DOI: 10.1093/jhered/esl053.
Pielberg, G., Andersson, L. :
Gene copy number detection in animal studies. Methods Mol Biol 373:147-56, 2007. Pubmed reference: 17185764.
Seo, BY., Park, EW., Ahn, SJ., Lee, SH., Kim, JH., Im, HT., Lee, JH., Cho, IC., Kong, IK., Jeon, JT. :
An accurate method for quantifying and analyzing copy number variation in porcine KIT by an oligonucleotide ligation assay. BMC Genet 8:81, 2007. Pubmed reference: 18036219. DOI: 10.1186/1471-2156-8-81.
2006 Fésüs, L., Sarlós, P., Osváth, Z., Zsolnai, A., Komlósi, I., Rátky, J. :
Influence of the dominant white/KIT genotypes on the reproductive organs of pigs. J Reprod Dev 52:707-13, 2006. Pubmed reference: 16960427.
Shi, KR., Wang, AG., Yuan, XF., Deng, XM., Li, N. :
Analysis of the MC1R, KIT and ASIP loci in Chinese and European pigs. Anim Genet 37:300-2, 2006. Pubmed reference: 16734703. DOI: 10.1111/j.1365-2052.2006.01446.x.
2005 Johansson, A., Pielberg, G., Andersson, L., Edfors-Lilja, I. :
Polymorphism at the porcine Dominant white/KIT locus influence coat colour and peripheral blood cell measures. Anim Genet 36:288-96, 2005. Pubmed reference: 16026338. DOI: 10.1111/j.1365-2052.2005.01320.x.
2003 Pielberg, G., Day, AE., Plastow, GS., Andersson, L. :
A sensitive method for detecting variation in copy numbers of duplicated genes. Genome Res 13:2171-7, 2003. Pubmed reference: 12952884. DOI: 10.1101/gr.1188203.
2002 Giuffra, E., Tornsten, A., Marklund, S., Bongcam-Rudloff, E., Chardon, P., Kijas, J.M.H., Anderson, S.I., Archibald, A.L., Andersson, L. :
A large duplication associated with dominant white color in pigs originated by homologous recombination between LINE elements flanking KIT Mammalian Genome 13:569-577, 2002. Pubmed reference: 12420135. DOI: 10.1007/s00335-002-2184-5.
Pielberg, G., Olsson, C., Syvanen, A.C., Andersson, L. :
Unexpectedly high allelic diversity at the KIT locus causing dominant white color in the domestic pig Genetics 160:305-311, 2002. Pubmed reference: 11805065.
1999 Giuffra, E., Evans, G., Tornsten, A., Wales, R., Day, A., Looft, H., Plastow, G., Andersson, L. :
The Belt mutation in pigs is an allele at the Dominant white (I/KIT) locus Mammalian Genome 10:1132-1136, 1999. Pubmed reference: 10594235.
1998 Marklund, S., Kijas, J., Rodriguezmartinez, H., Ronnstrand, L., Funa, K., Moller, M., Lange, D., Edforslilja, I., Andersson, L. :
Molecular basis for the dominant white phenotype in the domestic pig Genome Research 8:826-833, 1998. Pubmed reference: 9724328.
1996 Inoue, K., Tanaka, S., Kashiwazaki, N., Nakao, H., Nakatsuji, N., Sakaki, N., Tojo, H., Tachi, C. :
Quantitative analysis of striped coat-color patterns in large white-]duroc chimeric pigs with special reference to the genetic control mechanisms of the dominant black-eyed white phenotype Pigment Cell Research 9:289-297, 1996. Pubmed reference: 9125752.
Johansson Moller, M., Chaudhary, R., Hellmén, E., Höyheim, B., Chowdhary, B., Andersson, L. :
Pigs with the dominant white coat color phenotype carry a duplication of the KIT gene encoding the mast/stem cell growth factor receptor. Mamm Genome 7:822-30, 1996. Pubmed reference: 8875890.
Sakurai, M., Zhou, J.H., Ohtaki, M., Itoh, T., Murakami, Y., Yasue, H. :
Assignment of c-kit gene to swine chromosome 8P12-P21 by fluorescence in situ hybridization Mammalian Genome 7:397, 1996. Pubmed reference: 8661742.
1992 Johansson, M., Ellegren, H., Marklund, L., Gustavsson, U., Ringmarcederberg, E., Andersson, K., Edfors-Lilja, I., Andersson, L. :
The Gene for Dominant White Color in the Pig Is Closely Linked to ALB and PDGFRA on Chromosome-8 Genomics 14:965-969, 1992. Pubmed reference: 1362182.
1979 Lauvergne, J.J., Canope, I. :
Study of some colour variants of Creole pigs from Guadeloupe [French] Annales de Genetique Selection Animale 11:381-390, 1979.
1948 Hetzer, H.O. :
Inheritance of coat colour in swine. VII. Results of Landrace by Hampshire crosses. J Hered 39:122-8, 1948. Pubmed reference: 18865775.
1946 Hetzer, H.O. :
Inheritance of coat colour in swine. V. Results of Landrace by Duroc-Jersey crosses J Hered 37:217-24, 1946. Pubmed reference: 20281701.
1945 Hetzer, H.O. :
Inheritance of coat colour in swine. IV. Analysis of hybrids of Landrace and Large Black Journal of Heredity 36:309-312, 1945.
Hetzer, H.O. :
Inheritance of coat colour in swine. II. Results of Landrace by Poland China crosses Journal of Heredity 36:187-192, 1945.
Hetzer, H.O. :
Inheritance of coat colour in swine. III. Results of Landrace by Berkshire crosses Journal of Heredity 36:255-256, 1945.
1923 Wentworth, E.N., Lush, J.L. :
Inheritance in swine Journal of Agricultural Research 23:557-582, 1923.
1906 Spillman, W.J. :
Inheritance of color coat in swine. Science 24:441-3, 1906. Pubmed reference: 17801430. DOI: 10.1126/science.24.614.441.

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