OMIA 000209-9685 : Coat colour, dominant white in Felis catus

In other species: rabbit , pig , cattle , dog , horse , 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: 2014

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)

Species-specific name: Deaf white cat

Molecular basis: David et al. (2014) reported the causal mutation of dominant white to be an insertion of a long terminal repeat (LTR) of a feline endogenous retrovirus (FERV1) of the KIT gene.

This causal mutation was confirmed by Frischknecht et al. (2015).

Clinical features: As noted by Darwin in the first (1859) edition of Origin of Species, "What can be more singular than the relation between blue eyes and deafness in cats"? (page 144). In the second volume of his 1868 book entitled The Variation of Plants and Animals Under Domestication, he also mentioned the association with white coat colour: "white cats with blue eyes are almost always deaf" (page 354). This association has been much studied since then, but it is still poorly understood. Available data (summarised by Strain, 2007) suggests that the incidence of deafness amongst white cats is around 50%, comprising 40% bilateral and 10% unilateral. For cats with two, one or no blue eyes, the incidence of deafness (both bilateral and unilateral) is around 70%, 40% and 20%, respectively. And in one of the best-documented studies, Bergsma and Brown (1971) reported that around 40% of white cats have blue eyes. A segregation analysis of deafness and blue eyes by Geigy et al. (2007) suggested a gene of major effect affecting both traits, but this conclusion may be compromised by inbreeding in the population studied.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Felis catus B1 NC_018726.3 (164039337..163952966) 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
Domestic Longhair Coat colour, dominant white KIT insertion, gross (>20) B1 "a FERV1 long terminal repeat (LTR) is associated with all Dominant White individuals" 2014 25085922

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.
2015 Frischknecht, M., Jagannathan, V., Leeb, T. :
Whole genome sequencing confirms KIT insertions in a white cat. Anim Genet 46:98, 2015. Pubmed reference: 25515300. DOI: 10.1111/age.12246.
2014 David, V.A., Menotti-Raymond, M., Wallace, A.C., Roelke, M., Kehler, J., Leighty, R., Eizirik, E., Hannah, S.S., Nelson, G., Schäffer, A.A., Connelly, C.J., O'Brien, S.J., Ryugo, D.K. :
Endogenous retrovirus insertion in the KIT oncogene determines white and white spotting in domestic cats. G3 (Bethesda) 4:1881-91, 2014. Pubmed reference: 25085922. DOI: 10.1534/g3.114.013425.
2009 Cvejic, D., Steinberg, TA., Kent, MS., Fischer, A. :
Unilateral and bilateral congenital sensorineural deafness in client-owned pure-breed white cats. J Vet Intern Med 23:392-5, 2009. Pubmed reference: 19192155. DOI: 10.1111/j.1939-1676.2008.0262.x.
2007 Strain, G.M. :
Deafness in blue eyed white cats: the uphill road to solving polygenic disorders. Vet J 173:471-2, 2007. Pubmed reference: 17317244. DOI: 10.1016/j.tvjl.2006.01.015.
2004 Kretzmer, EA., Meltzer, NE., Haenggeli, CA., Ryugo, DK. :
An animal model for cochlear implants. Arch Otolaryngol Head Neck Surg 130:499-508, 2004. Pubmed reference: 15148168. DOI: 10.1001/archotol.130.5.499.
2003 Ryugo, DK., Cahill, HB., Rose, LS., Rosenbaum, BT., Schroeder, ME., Wright, AL. :
Separate forms of pathology in the cochlea of congenitally deaf white cats. Hear Res 181:73-84, 2003. Pubmed reference: 12855365.
2002 Ponton, CW., Eggermont, JJ. :
Of kittens and kids: altered cortical maturation following profound deafness and cochlear implant use. Audiol Neurootol 6:363-80, 2002. Pubmed reference: 11847464.
Redd, E.E., Cahill, H.B., Pongstaporn, T., Ryugo, D.K. :
The effects of congenital deafness on auditory nerve synapses: Type I and type II multipolar cells in the anteroventral cochlear nucleus of cats J Assoc Res Otolaryngol 3:403-417, 2002. Pubmed reference: 12486596. DOI: 10.1007/s101620020043.
2000 Christensen, A.C. :
Cats as an aid to teaching genetics. Genetics 155:999-1004, 2000. Pubmed reference: 10880464.
Redd, EE., Pongstaporn, T., Ryugo, DK. :
The effects of congenital deafness on auditory nerve synapses and globular bushy cells in cats. Hear Res 147:160-74, 2000. Pubmed reference: 10962182.
1998 Heid, S., Hartmann, R., Klinke, R. :
A model for prelingual deafness, the congenitally deaf white cat - population statistics and degenerative changes Hearing Research 115:101-112, 1998. Pubmed reference: 9472739.
Ryugo, D.K., Rosenbaum, B.T., Kim, P.J., Niparko, J.K., Saada, A.A. :
Single unit recordings in the auditory nerve of congenitally deaf white cats - morphological correlates in the cochlea and cochlear nucleus Journal of Comparative Neurology 397:532-548, 1998. Pubmed reference: 9699914.
1997 Hartmann, R., Shepherd, R.K., Heid, S., Klinke, R. :
Response of the primary auditory cortex to electrical stimulation of the auditory nerve in the congenitally deaf white cat Hearing Research 112:115-133, 1997. Pubmed reference: 9367234.
Heid, S., Jähn-Siebert, T.K., Klinke, R., Hartmann, R., Langner, G. :
Afferent projection patterns in the auditory brainstem in normal and congenitally deaf white cats. Hear Res 110:191-9, 1997. Pubmed reference: 9282901.
Huchton, DM., Pongstaporn, T., Niparko, JK., Ryugo, DK. :
Ultrastructural changes in primary endings of deaf white cats. Otolaryngol Head Neck Surg 116:286-93, 1997. Pubmed reference: 9121779.
Ryugo, D.K., Pongstaporn, T., Huchton, D.M., Niparko, J.K. :
Ultrastructural analysis of primary endings in deaf white cats - morphologic alterations in endbulbs of held Journal of Comparative Neurology 385:230-244, 1997. Pubmed reference: 9268125.
1996 Saada, A.A., Niparko, J.K., Ryugo, D.K. :
Morphological changes in the cochlear nucleus of congenitally deaf white cats Brain Research 736:315-328, 1996. Pubmed reference: 8930338.
1992 Larsen, SA., Kirchhoff, TM. :
Anatomical evidence of synaptic plasticity in the cochlear nuclei of white-deaf cats. Exp Neurol 115:151-7, 1992. Pubmed reference: 1728561.
1987 Wagner, A., Wolsan, M. :
Pelage mutant allele frequencies in domestic cat populations of Poland. J Hered 78:197-200, 1987. Pubmed reference: 3611716.
1982 Schwartz, IR., Higa, JF. :
Correlated studies of the ear and brainstem in the deaf white cat: changes in the spiral ganglion and the medial superior olivary nucleus. Acta Otolaryngol 93:9-18, 1982. Pubmed reference: 7064701.
1981 Rebillard, M., Pujol, R., Rebillard, G. :
Variability of the hereditary deafness in the white cat. II. Histology. Hear Res 5:189-200, 1981. Pubmed reference: 7309638.
Rebillard, M., Rebillard, G., Pujol, R. :
Variability of the hereditary deafness in the white cat. I. Physiology. Hear Res 5:179-87, 1981. Pubmed reference: 7309637.
1980 Pedersen, EK., Mair, IW., Elverland, HH. :
Hereditary deafness in the cat: an electron-microscopic study of the tectorial membrane. Arch Otorhinolaryngol 229:55-68, 1980. Pubmed reference: 7469938.
1977 Pujol, R., Rebillard, M., Rebillard, G. :
Primary neural disorders in the deaf white cat cochlea. Acta Otolaryngol 83:59-64, 1977. Pubmed reference: 842327.
1976 Rebillard, G., Rebillard, M., Carlier, E., Pujol, R. :
Histo-physiological relationships in the deaf white cat auditory system. Acta Otolaryngol 82:48-56, 1976. Pubmed reference: 948985.
1975 Elverland, HH., Godtliebsen, OB., Kayed, K., Mair, IW. :
Non-surgical recording of auditory pathway function in cats. Arch Otorhinolaryngol 211:249-57, 1975. Pubmed reference: 1243645.
1973 Mair, IW. :
Hereditary deafness in the white cat. Acta Otolaryngol Suppl 314:1-48, 1973. Pubmed reference: 4363431.
West, C.D., Harrison, J.M. :
Transneuronal cell atrophy in the congenitally deaf white cat Journal of Comparative Neurology 151:377-398, 1973. Pubmed reference: 4754840. DOI: 10.1002/cne.901510406.
1971 Bergsma, D.R., Brown, K.S. :
White fur, blue eyes and deafness in the domestic cat Journal of Heredity 62:171-185, 1971. Pubmed reference: 5137350.
Brown, KS., Bergsma, DR., Barrow, MV. :
Animal models of pigment and hearing abnormalities in man. Birth Defects Orig Artic Ser 07:102-9, 1971. Pubmed reference: 5173333.
1966 Bosher, SK., Hallpike, CS. :
Observations on the histogenesis of the inner ear degeneration of the deaf white cat and its possible relationship to the aetiology of certain unexplained varieties of human congenital deafness. J Laryngol Otol 80:222-35, 1966. Pubmed reference: 5907833.
Todd, NB. :
The independent assortment of dominant white and polydactyly in the cat. J Hered 57:17-18, 1966. Pubmed reference: 5917255.
1965 Bosher, SK., Hallpike, CS. :
OBSERVATIONS ON THE HISTOLOGICAL FEATURES, DEVELOPMENT AND PATHOGENESIS OF THE INNER EAR DEGENERATION OF THE DEAF WHITE CAT. Proc R Soc Lond B Biol Sci 162:147-70, 1965. Pubmed reference: 14285813.
1942 Wolff, D. :
Three generations of deaf white cats Journal of Heredity 33:39-43, 1942.
1918 Wright, S. :
Color inheritance in mammals. X. The cat - Curious association of deafness with blue-eyed white color and femaleness with tortoise-shelled color, long known - variations of tiger pattern present in interesting features Journal of Heredity 9:139-144, 1918.
1884 Bell, A.G. :
Deafness in white cats, and statistics of deafness and epilepsy in America. Science 3:243-4, 1884. Pubmed reference: 17808809. DOI: 10.1126/science.ns-3.56.243-a.
Bell, A.G. :
Deafness in white cats. Science 3:171, 1884. Pubmed reference: 17738188. DOI: 10.1126/science.ns-3.54.171.
1883 Tait, L. :
Notes on Deafness in White Cats Nature 29:164 only, 1883. DOI: 10.1038/029164a0.
1873 Tait, L. :
Note on a Polydactylous Cat from Cookham-Dean. Nature 7:323 only, 1873. DOI: 10.1038/007323b0 .

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  • Created by Frank Nicholas on 09 Sep 2008
  • Changed by Frank Nicholas on 29 Aug 2014
  • Changed by Frank Nicholas on 16 Apr 2015