SHORT COMMUNICATION
doi:10.1111/j.1365-2052.2005.01389.x
White spotting in the domestic cat (Felis catus) maps near KIT on
feline chromosome B1
M. P. Cooper*, N. Fretwell†, S. J. Bailey† and L. A. Lyons*
*Population Health and Reproduction, School of Veterinary Medicine, University of California – Davis, Davis, CA 95616 USA. †WALTHAM
Centre for Pet Nutrition, Melton Mowbray, Leics, UK
OnlineOpen: This article is available free online at www.blackwell-synergy.com
Summary
Five feline-derived microsatellite markers were genotyped in a large pedigree of cats that
segregates for ventral white spotting. Both KIT and EDNRB cause similar white spotting
phenotypes in other species. Thus, three of the five microsatellite markers chosen were on
feline chromosome B1 in close proximity to KIT; the other two markers were on feline
chromosome A1 near EDNRB. Pairwise linkage analysis supported linkage of the white
spotting with the three chromosome B1 markers but not with the two chromosome A1
markers. This study indicates that KIT, or another gene within the linked region, is a
candidate for white spotting in cats. Platelet-derived growth factor alpha (PDGFRA) is also a
strong candidate, assuming that the KIT–PDGFRA linkage group, which is conserved in
many mammalian species, is also conserved in the cat.
Keywords cat, feline, KIT, PDGFRA, spotting, white.
White spotting pelage and skin phenotypes have been
investigated in a variety of mammals. In cats, the white
spotting locus (S), appears to affect melanocyte migration.
Heterozygous animals (Ss) have a ventral white pattern
(Whiting 1919), not spots, as the name would suggest. This
ventral white pattern, known as bicolour by cat fanciers, is
considered to be dominant to solid colour, with an additive
effect of the dominant allele. Full solid colour (ss) is recessive, while the van pattern, in which colour is limited to the
head and tail regions, is postulated as homozygous SS
(Kuhn & Kroning 1928). Various other white spotting
phenotypes show spotting at the ventral midline, such as
lockets and belly spots, or white at the extremities, such as
gloves and mittens. These other white presentations are
anticipated to be allelic to ventral white (Whiting 1919). In
addition, dominant white (W), which is associated with blue
eye colour and deafness in the cat, may be allelic to white
spotting (Whiting 1919; Bergsma & Brown 1971); however, epistasis has complicated allele assignments.
The gene(s) responsible for white spotting in the domestic
cat have not yet been identified. In several mammals,
mutations in loci including EDNRB, KIT and PDGFRA
(Smith et al. 1991; Stephenson et al. 1991, 1998) have
Address for correspondence
L. A. Lyons, Population Health and Reproduction, School of Veterinary
Medicine, University of California – Davis, Davis, CA 95616 USA.
E-mail: [email protected]
Accepted for publication 18 September 2005
been shown to be causative for the dominant white and/or
the white spotting phenotypes. We hypothesized that
mutations in EDNRB, KIT, or PDGFRA control at least one
type of white spotting pattern in the domestic cat, and we
performed a linkage analysis of ventral (bicolour) white
spotting using a panel of five microsatellites spanning these
three genes.
An extended pedigree of 114 cats segregating for white
spotting (Fig. S1) from the WALTHAM Centre for Pet
Nutrition (Melton Mowbray, Leics, UK) was used for the
linkage analysis. Three white spotting cat phenotypes were
assigned according to the white pattern grading system
proposed by Robinson (1959): solid, bicoloured and van
(Fig. 1). Solid coloured cats had no evidence of white spotting. Bicolour cats had a ventral white pattern with
approximately 50% or more of the coat having pigment.
Van patterned cats had small spots of colour near the head
and tail, and occasionally one or a few pigmented spots on
the dorsal or lateral side; hence a more extreme white
expression than bicolour. Buccal cells were obtained noninvasively by swabbing the internal cheek of each cat with a
cytological brush. DNA was extracted as previously described (Oberbauer et al. 2003).
Five feline-derived microsatellites (FCA097, FCA149,
FCA152, FCA229 and FCA453) that flanked KIT and
EDNRB were selected from the feline linkage (MenottiRaymond et al. 1999, 2003) and radiation hybrid (Murphy
et al. 2000) maps. PDGFRA is not mapped in the cat;
however, a KIT-PDGFRA linkage group is found in several
2005 The Authors, Journal compilation 2005 International Society for Animal Genetics, Animal Genetics, 37, 163–165
163
164
Cooper et al.
the white spotting locus was conducted as previously described (Lyons et al. 2005) using the LINKAGE software
program (Lathrop et al. 1984). The expression of bicolour
and van was highly variable, so a clear distinction between
bicolour vs. van was difficult for a few cats. Thus, the
linkage analysis was conducted by coding the non-white,
solid coloration as a homozygous recessive trait with complete penetrance and non-variable expression.
All pairwise analyses are presented in Table 1. Significant
linkage was found between microsatellite FCA097 and
white spotting (Z ¼ 9.072, h ¼ 0.04). Pairwise analyses
supported linkage of FCA149 and FCA152 to FCA097. In
addition, FCA149 and FCA152 appeared to be linked to the
white spotting locus, although the LOD scores were not significant. FCA097, which we predicted to be 4 cM from white
spotting, was previously demonstrated to be approximately
22.15 cM centromeric to KIT (Menotti-Raymond et al.
2003). PDGFRA has not been localized to feline chromosome B1; however, the KIT-PDGFRA linkage group is highly
conserved in other species. Additional markers would help
to resolve the genetic map of the cat in this region and
to better define the positions of KIT, PDGFRA and white
spotting.
Additionally, two markers on cat chromosome A1 near
EDNRB were excluded for linkage with white spotting
(Z £ )2.0, h £ 0.199 for FCA229; Z £ )2.0, h £ 0.233 for
FCA453). Based on the radiation hybrid map, one marker,
FCA229, is 5.05 cM from EDNRB; thus, the excluded
region surrounding this marker suggests that EDNRB does
not influence the white spotting phenotype in cats.
This study examined a closed cat colony. A caveat to
using a closed colony or family is that the linkage between microsatellites and white spotting could be specific
to that colony or family. White spotting is a heterogeneous phenotype, and similar colour patterns found in other
families may be caused by different genes. Testing for
linkage in families of different breeds could provide additional evidence for KIT or PDGFRA as candidate genes for
white spotting in cats. Further investigations of the genes
near FCA097 are necessary to provide conclusive evidence of their contribution to white spotting in the
domestic cat.
Figure 1 White spotting classifications in the WALTHAM pedigree.
(a) High white or van patterned, (b) bicolour pattern and (c) solid colour
pattern.
mammalian species. Thus, the analysis of markers near KIT
would also likely implicate PDGFRA in the cat. Three of the
markers (FCA097, FAC149 and FCA152) were on feline
chromosome B1 within close proximity to the KIT-PDGFRA
region, whereas two of the markers (FCA229 and FCA453)
were on feline chromosome A1 near EDNRB. Genotyping of
these markers was as performed as described by Grahn et al.
(2004). Two-point linkage between the microsatellites and
Acknowledgements
Funding for this project was provided to L. A. Lyons from
NIH-NCRR RR016094, the Winn Feline Foundation, and
the George and Phyllis Miller Feline Health Fund, Center for
Companion Animal Health, School of Veterinary Medicine,
University of California, Davis. We acknowledge the National Cancer Institute for allocation of computing time and
staff support at the Advanced Biomedical Computing Center
of the Frederick Cancer Research and Development Center.
Technical assistance for the project was provided by Mark T.
Ruhe and Carolyn A. Erdman.
2005 The Authors, Journal compilation 2005 International Society for Animal Genetics, Animal Genetics, 37, 163–165
White spotting in F. catus
Table 1 LOD scores for pairwise comparisons between white spotting and microsatellite markers.
Recombination rate, Q
Marker 1
Marker 2
0.00
0.01
0.05
0.10
0.20
0.30
Max LOD, Z
Q at Max LOD, Z
Q at Z ¼ )2.0
Spotting
Spotting
Spotting
Spotting
Spotting
FCA097
FCA097
FCA149
FCA299
FCA299
FCA299
FCA453
FCA453
FCA453
FCA097
FCA149
FCA152
FCA229
FCA453
FCA149
FCA152
FCA152
FCA097
FCA149
FCA152
FCA097
FCA149
FCA152
)¥
)¥
)¥
)¥
)¥
)¥
)¥
)¥
)¥
)¥
)¥
)¥
)¥
)¥
8.52
0.23
)5.79
)13.13
)17.82
0.24
)1.73
)5.58
)28.55
)30.11
)33.62
)24.99
)33.27
)28.74
9.05
1.85
)0.60
)6.96
)9.09
4.84
4.28
3.62
)13.94
)15.22
)16.91
)11.62
)16.39
)13.39
8.53
2.15
1.27
)4.36
)5.62
5.95
5.98
6.43
)8.29
)9.23
)10.32
)6.40
)9.65
)7.42
6.75
1.85
2.16
)1.98
)2.59
5.62
6.12
7.23
)3.60
)3.97
)4.63
)2.12
)3.84
)2.50
4.54
1.22
1.70
)0.87
)1.13
4.06
4.64
5.73
)1.62
)1.61
)2.01
)0.51
)1.34
)0.61
9.07
2.16
2.16
–
–
6.07
6.35
7.33
–
–
–
–
–
–
0.04
0.11
0.20
–
–
0.13
0.15
0.17
–
–
–
–
–
–
–
–
–
0.20
0.23
–
–
–
0.27
0.28
0.30
0.21
0.27
0.22
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Supplementary Material
The following supplementary material is available for this
article online at http://www.blackwell-synergy.com
Figure S1. WALTHAM cat pedigree segregating for white
spotting.
2005 The Authors, Journal compilation 2005 International Society for Animal Genetics, Animal Genetics, 37, 163–165
165