Download Microsatellite mapping of the bovine roan locus: a major determinant

Mammalian Genome 7, 138–142 (1996).
© Springer-Verlag New York Inc. 1996
Microsatellite mapping of the bovine roan locus: a major determinant
of White Heifer Disease
C. Charlier,1 B. Denys,1 J.I. Belanche,1 W. Coppieters,1 L. Grobet,1 M. Mni,1 J. Womack,2 R. Hanset,1
M. Georges1
1
2
Département de Génétique, Faculté de Médecine Vétérinaire, Université de Liège, 20 Boulevard de Colonster (B43), B4000-Liège, Belgium
Department of Veterinary Pathobiology, Texas A&M, College Station, Texas, USA
Received: 30 May 1995 / Accepted: 6 September 1995
Abstract. In the Belgian Blue Cattle breed, coat color variation is
mainly under the influence of a single autosomal locus, the roan
locus, characterized by a pair of codominant alleles: r+ (black) and
R (white). Heterozygous r+R animals have intermingled black and
white hairs, yielding the ‘‘blue’’ phenotype typical of the breed.
Major interest for the roan locus stems from its pleiotropic effect
on fertility, owing to the critical role of the R allele in the determinism of White Heifer Disease. We describe the linkage mapping
of the roan locus to bovine Chromosome (Chr) 5, in the interval
between microsatellite markers BPI and AGLA293, with an associated lodscore of 11.2. Moreover, we map a candidate gene, the
Steel locus coding for the mast cell growth factor, to bovine Chr 5.
Introduction
Despite its name, the Belgian Blue cattle breed is characterized by
a coat color polymorphism dominated by three distinct phenotypes: black spotted, blue spotted, and white animals (Fig. 1).
Closer scrutiny of the pigmented sectors in blue animals reveals a
mixture of black and white hairs. This trimorphism is reminiscent
of the well-known coat color pattern found in the Shorthorn breed
with its red spotted, roan (red and white hairs intermingled) spotted, and white individuals. As early as 1905, Barrington and Pearson (1906) used segregation data of these Shorthorn phenotypes to
test Mendel’s theory of particulate inheritance. A model assuming
a single diallelic locus with two codominant alleles fitted the observed segregation ratios reasonably well. However, the occurence
of a nonneglectable proportion of cases violating Mendel’s rules
led Barrington and Pearson to question the relevance of Mendel’s
theory. Subsequently several authors proposed more elaborate
models to account for the occasional exceptions (for example,
Evvard et al. 1930), but it was Wright (1917) who concluded that
if the more complicated models explained the exceptions, the original simple model proposed, though questioned by Barrington and
Pearson themselves, explained the overall data best by far, and that
it was, therefore, likely that one autosomal locus with a pair of
codominant alleles played a major role in the determination of the
observed trimorphism.
More recently, Hanset (1959, 1985) pointed towards the close
resemblance between the segregation ratios observed in the Belgian Blue cattle breed for the black, blue, and white phenotypes,
and in the Shorthorn breed for the red, roan, and white phenotypes.
As Wright did earlier in Shorthorn, Hanset concluded from these
studies that a single diallelic locus–the roan locus–, with codominant alleles r+ (black) and R (white), was superior to any other
Correspondence to: C. Charlier
model in explaining the overall observations. Exceptions could
virtually all be accounted for by assuming incomplete penetrance
for the Rr+ or blue genotype, a proportion of Rr+ animals being
recorded as white (.9%) or black (.9%). This is actually not
unexpected in light of the documented variation in the ratio of
white to black hairs in blue sectors, yielding very light to dark blue
animals. Circumstantial evidence indicates that this varying blackto-white-hair ratio may be under genetic control, but to the best of
our knowledge this has not been studied in detail. Moreover, while
in the Belgian Blue cattle breed the recessive s allele at the Self
locus [responsible for piebald spotting, (e.g., Ibsen 1993)] is virtually fixed, there is substantial variation in the expressivity of the
piebald trait, with some extreme animals being nearly completely
devoid of pigmented sectors. Finally, some poorly characterized
phenotypes such as the ‘‘colorsided’’ spotting attributed to the
segregation of a dominant Sc factor at the same Self locus (Wriedt,
1925), are segregating in the Belgian Blue population at low frequency, potentially complicating the classification of animals into
discrete phenotypic classes.
The segregation of the same roan locus in both the Shorthorn
and Belgian Blue cattle breed would not be surprising given the
important migration of Shorthorn genes that occurred into the Belgian cattle population during the 19th century. The fact that the
pigmented hairs are red in Shorthorn while black in the Belgian
Blue reflects the high frequency of the dominant E allele at the
Extension locus (Charlier et al. 1995b), probably imported through
Dutch black and white animals. Occasionally, however, red spotted or red-roan spotted animals are still encountered in the Belgian
Blue breed, pointing towards the segregation of the e allele or ‘‘red
factor’’ in this population albeit at low frequency.
Besides the fact that it attracted the attention of famous geneticists in the beginning of this century, the roan locus has intrigued
scientists because of its predominant role in the determinism of
White Heifer Disease. This disorder is characterized by a range of
anomalies of the female genital tract resulting from the aberrant
development of the Müllerian ducts. Lesions include the occurrence of a posterior vaginal occlusion, absence or incompletely
developed vagina, cervix, uterine body, and one or both uterine
horns; these different lesions occur either isolated or in conjunction. Ovaries are invariably found not to be affected in White
Heifer Disease (Hanset and Ansay 1961).
As its name implies, a striking feature of this disorder is its
high frequency in association with the white coat color phenotype
in cattle populations segregating for the roan locus. These include
in particular the Shorthorn and Belgian Blue cattle breeds. In the
Belgian Blue cattle breed, more than 90% of affected animals have
the white phenotype, the remainder being more often blue than
black. Studies in this breed (Hanset 1969a) led to the conclusion
that White Heifer Disease has a multifactorial basis, including
genetic and environmental components. The roan locus would be
C. Charlier et al.: Bovine roan locus and White Heifer Disease
139
Fig. 1. Illustration of the coat-color polymorphism segregating in the Belgian Blue cattle population, characterized by the three genotypes: white, black,
and blue.
the major genetic determinant, acting in conjunction with one or,
more probably, several auxiliary genes. The heritability of the
defect within the white phenotype has been estimated at 0.2–0.25.
Evidence was given that the involvement of the roan locus is
probably due to a direct effect of the R allele, rather than to a
closely linked gene, or separate allele at the roan locus itself. In the
Belgian Blue cattle breed, the incidence of this disorder has been
as high as 5–10% of the cow population in the 1950s. Because of
systematic selection against the auxiliary genes, through the elimination of affected females and progeny testing of sires, the incidence of the disease has been reduced to 1.5% (Hanset 1969b).
In this paper, we describe the localization of the bovine roan
locus to Chromosome (Chr) 5, in the interval between microsatellite markers BP1 and AGLA293. Since the linkage analysis was
based on the hypothesis of a simple monogenic determinism of the
coat color trimorphism with two codominant alleles r+ (black) and
R (white), this study supports the validity of the corresponding
model. Moreover, using somatic cell hybrids, we map a candidate
gene, the Steel locus coding for the ligand of the c-kit tyrosine
kinase receptor, to the same bovine chromosome.
Materials and methods
Pedigree material: the ‘‘Sart-Tilman’’ pedigree. To map the roan
locus, we used a pedigree composed of six white Belgian Blue sires mated
to 37 black spotted Friesian cows. All six sires have been extensively
progeny tested in the Belgian Blue cattle population, and their proportions
of white, blue, and black offspring indicate that they are all of the RR
genotype. Conversely, all Friesian cows are assumed to be of r+r+ genotype, as the roan phenotype is not segregating in this population. The
resulting 37 ‘‘F1’’ cows were all phenotypically blue, as predicted from the
monogenic model with a pair of codominant alleles. The F1 r+R cows were
backcrossed to three progeny-tested white Belgian Blue sires (RR), yielding 105 backcross (BC) offspring segregating at the roan locus. ‘‘F1’’ and
‘‘BC’’ animals were held at the Sart-Tilman experimental station and
phenotyped for coat color by repeated visual examination; 59 blue spotted
and 46 white BC offspring were obtained (x21 = 1.6, p ≈ 0.2).
The described animals are part of a larger pedigree (the Sart-Tilman
pedigree) initially constructed to map the mh locus (Charlier et al. 1995a).
One branch of this pedigree was ignored in this analysis as it segregates for
the ‘‘colorsided’’ or Sc factor (Wriedt, 1925) that interacts with the expression of the roan locus.
The IBRP panel of international bovine reference families was used for
map construction (Barendse et al. 1994).
Marker genotyping. A battery of 213 microsatellite markers distributed
over the 29 bovine autosomes and compiled from three partially overlap-
ping and recently published bovine maps (Barendse et al. 1994; Bishop et
al. 1994; Georges et al. 1995), was chosen to allow for a systematic
scanning of the bovine genome. The primer sequences used for the amplification of the Chr 5 microsatellites are reported in Table 1. Microsatellite genotyping was performed essentially as previously reported
(Georges et al. 1995).
Linkage analysis. Linkage analyses were performed on a Sun Sparc
Classic workstation with version 5.0 of the LINKAGE programs (Lathrop
and Lalouel 1984). To deal with the large number of marriage loops, the
‘‘roan’’ pedigree was split into 37 nuclear families, each corresponding to
a single F1 cow, with respective Belgian Blue sire, Friesian dam, Belgian
Table 1. Primer sequences used for the amplification of the seven chromosome
5-specific microsatellite markers.
BM6026.UP1
BM6026.DN1
BP1.UP1
BP1.DN1
AGLA293.UP1
AGLA293.DN1
AGLA254.UP1
AGLA254.DN1
IGFL.UP1
IGFI.DN1
BM315.UP1
BM315.DN1
GCAAGTAAGACCCAACCAAC
ACTGATGTGCTCAGGTATGACG
AAAATCCCTTCATAACAGTGCC
CATCGTGAATTCCAGGGTTC
GAAACTCAACCCAAGACAACTCAAG
ATGACTTTATTCTCCACCTAGCAGA
GCTGCTTGGCACAGGCAAA
GGATTAATTTCTGGACTCTG
GGGTATTGCTAGCCAGCTGGT
CATATTTTTCTGCATAACTTGAACCT
TGGTTTAGCAGAGAGCACATG
GCTCCTAGCCCTGCACAC
Fig. 2. Sequence alignment of the fifth exon of the bovine (Zhou et al.
1994), human (Martin et al. 1990), and murine (Brannan et al. 1992) mast
cell growth factor gene. The location of the primers used to generate a
bovine-specific 106-bp STS are underlined.
140
C. Charlier et al.: Bovine roan locus and White Heifer Disease
Table 2. Lodscore tables obtained by pair-wise linkage analysis between the roan locus and the corresponding Chr 5
microsatellite marker. The IGFI microsatellite proved monomorphic in our pedigree material, therefore yielding no
information (NI).
u
Marker
0
0.01
0.05
0.1
0.2
0.3
0.40
BM6026
BP1
AGLA293
AGLA254
IGFI
BM315
−`
−`
−`
−`
NI
−`
−0.93
11.10
0.83
−24.55
NI
−51.67
3.85
11.47
3.14
−9.40
NI
−27.10
5.20
10.75
3.70
−3.67
NI
−17.03
5.32
8.56
3.53
0.70
NI
−7.86
4.20
5.91
2.73
1.92
NI
−3.39
2.39
2.97
1.54
1.57
NI
−1.02
Fig. 3. Lodscore curve obtained with the LINKMAP program (Lathrop and Lalouel 1984), by sliding the roan locus through the fixed Chr 5 marker
map. Recombination rates between adjacent markers were converted to centiMorgan with Haldane’s mapping function.
Blue mate(s), and resulting BC offspring. Coat color phenotypes were
encoded as a ‘‘numbered alleles’’ system (11: white; 12: blue; 22: black),
or as an ‘‘affection status’’ (1: white; 2: blue or black) to test the effects of
misclassification by varying the penetrance for the three different genotypes.
Synteny mapping of the Steel locus. Primers that should amplify part
of exon 5 of the bovine Steel gene were designed from the published
bovine stem cell factor cDNA sequence (Zhou et al. 1994), assuming
conservation of intron position between bovine, human, and mice. The
primers were targeted towards poorly conserved segments of the exon to
specifically amplify bovine product, while avoiding cross-amplification of
rodent product in particular (Fig. 2). These primers were shown to amplify
the expected 106-bp fragment from bovine genomic DNA, while yielding
no product from genomic DNA of the rodent species used to construct the
somatic cell hybrid panel (data not shown).
A previously described panel of somatic cell hybrids (Dietz et al. 1992)
was tested for the segregation of this Steel STS. The resulting segregation
patterns were analyzed according to Chevalet and Carpet (1986).
Results
To find a marker for the roan locus, we undertook a systematic
chromosome-by-chromosome genome scan, using a selected panel
of 213 microsatellite markers (see Materials and methods) spread
across the bovine autosomes with average spacing of 15 cM. Sequential pair-wise linkage analysis was performed between the
genotyped microsatellite markers and the roan locus, with the
MLINK program. When a set of seven markers covering bovine
Chr 5 was screened, four of the tested markers yielded positive
pair-wise lodscores with roan: BM6026, BP1, AGLA293, and
AGLA254 (Table 2). According to previously published maps
(Bishop et al. 1994; Georges et al. 1995), these correspond to the
microsatellites located on the centromeric side of the Chr 5 linkage
group.
To more precisely determine the relative map positions of
these four microsatellites, we genotyped the IBRP pedigrees with
the corresponding markers. Genotypic data from the roan and
IBRP pedigrees were combined to construct male and female linkage maps using the ILINK program. Maximum likelihood order
and associated male and female recombination rates between adjacent markers, for the centromeric side of the Chr 5 microsatellite
map, are respectively: Cen–BM6026(14.1-8.2)–BP1(23.3-10.3)–
AGLA293(22.8-40.6)–AGLA254. The most likely locus order
given our data set is in agreement with a previously reported map
of bovine Chr 5 involving the same markers (Bishop et al. 1994).
The odds versus the next most likely order (positioning AGLA254
on the centromeric side of the linkage group) was 69:1 given our
data. To position the roan locus on the established map, its location
was varied with respect to the microsatellite markers held at fixed
positions, and corresponding lodscores were computed with
LINKMAP (Fig. 3). As all informative meioses for the segregation
of the roan locus were female, the position of this locus is given
with respect to the female marker map. This analysis points towards the most likely position of the roan locus in the interval
between BP1 and AGLA293, at 3.7 cM from the former and with
an associated lodscore of 11.2. Positions yielding a lodscore one
unit below the maximum of 11.2 roughly define a 95% confidence
interval of 11.8 cM.
As deviations from a strictly Mendelian inheritance pattern
have repeatedly been documented for the studied coat color tri-
C. Charlier et al.: Bovine roan locus and White Heifer Disease
141
Table 3. Effect of misclassification on the positioning of the roan locus with respect
to microsatellite marker BP1, and on the likelihood of the pedigree data.
% Misclassification
Distance from BP1 (cM)
Odds
0
2.5
5
10
3.7
2.8
1
0
1
2.6
3.3
1.3
morphism, we looked for evidence of phenotypic misclassifications in the analyzed data set. Frequent misclassification would
manifest itself by a high incidence of double recombinants. Analysis of the individual genotypes revealed only one such offspring
in the BP1–roan–AGLA293 chromosome segment assuming that
order, which is not unexpected given the number of analyzed
backcross offspring (108) and the estimated distance between BP1
and AGLA293 (10.3%). Moreover, a high incidence of double
recombinants would confuse the multipoint analysis, generating
discrepancies with the two-point analysis. It can be seen that the
closest microsatellite marker as determined by two-point analysis
(BP1) also appears as the closest marker when performing multipoint analysis. To more formally address the misclassification
issue, lodscore curves were regenerated with LINKMAP as described, but allowing for a varying percentage of misclassification
in the backcross generation, that is, 2.5%, 5%, or 10% of genetically white (RR) offspring would be classified as blue (r+R), and
vice versa. The genotypes of the parental and F1 generations were
considered unambiguous, as all used Belgian Blue sires (RR) have
been progeny tested for coat color genotype in the commercial
population, and the Black and White Friesian dams come from a
monomorphic black (r+r+) population. As shown in Table 3, allowing for misclassification yielded for a marginal increase in
likelihood at best, while shifting the roan locus closer to BP1.
Altogether, these results point towards absence of significant phenotypic misclassification in our data set.
As microsatellite marker BP1 was shown to be very closely
linked to the myogenic factor-5 (Myf5) gene (Bishop et al. 1994),
the present linkage study positions the roan locus to a chromosome
segment bounded by two anchored reference loci: Myf5 and IGFI.
These two type I markers are also syntenic in human as well as
mice, where they map to Chr 12 and 10 respectively (Taylor et al.
1993). Intriguingly, the corresponding chromosome segment is
know to harbor the Sl or Steel locus in mice, positioned at approximately 8.5 cM from Myf5 and 11 cM from IGFI (Taylor et al.
1993). The Sl locus codes for the mast cell growth factor (Brannan
et al. 1992), and mutations at this locus invariably affect coat color
pigmentation (Green 1990). Although the phenotypic expression
of the murine Sl mutations differs in several points from the bovine
roan phenotype and associated White Heifer Disease (see Discus-
sion), it would nevertheless qualify as a reasonable candidate gene
if it mapped to the corresponding chromosomal region. To start
answering that question, we typed a bovine somatic cell hybrid
panel for a bovine-specific Sequence Tagged Site developed from
the bovine stem cell factor cDNA sequences (see Materials and
methods). Table 4 summarizes the obtained results, clearly demonstrating that the homolog of the murine steel locus indeed maps
to bovine Chr 5.
Discussion
The observation of an entirely blue F1 generation obtained by
crossing white Belgian Blue sires with black Friesian dams, and
the subsequent 50%–50% segregation of blue and white offspring
in a backcross to white Belgian Blue sires, clearly supports a
monogenic hypothesis with a pair of codominant alleles to explain
the coat color trimorphism observed in the Belgian Blue Cattle
breed. This assumption is dramatically strengthened by the identification in this study of a genetic marker on bovine Chr 5 that
cosegregates with the postulated roan locus.
Given the similarities between the coat color polymorphism in
the Belgian Blue and Shorthorn populations, as well as the documented links between both populations, it is reasonable to extend
our conclusions to the Shorthorn population and to assume that the
same roan locus with the same r+ and R alleles determines the coat
color patterns observed in both breeds. The black versus red color
of pigmented hairs in Belgian Blue and Shorthorn respectively is
assumed to reflect the near fixation in both populations of different
alleles at the unlinked Extension locus. As the Extension locus has
recently been identified in cattle (Charlier, in preparation), this
hypothesis becomes easily testable.
Comparative mapping data allow us to predict that the bovine
roan locus maps to an evolutionary conserved chromosome segment bounded by the Myf5 and IGF-I loci. Interestingly, a possible
candidate for the bovine roan gene has previously been assigned to
this conserved chromosome fragment: the steel or Sl locus mapping to Chr 10 in mice.
Mutations at the Sl locus in mice (coding for the mast cell
growth factor, now known to be the ligand of the c-kit tyrosinase
kinase receptor), like mutations at the W locus (coding for the c-kit
tyrosinase kinase receptor), cause a reduction in pigmentation,
sterility, and macrocytic anemia (for example, Green 1990; Jackson 1994). Generally speaking, the reduction in pigmentation manifests itself as black-eyed white animals in homozygotes, and as a
diluted coat color with some white spotting in heterozygotes. The
coat color manifestations, however, are quite heterogeneous, and
features of some Sl or W mutations can be considered reminiscent
of the studied bovine coat color trimorphism. Indeed, black-eyed
white animals homozygous for a number of Sl and W mutations
Table 4.
Synt.
Chr.
Mark.
Conc.
Corr
Synt.
Chr.
Mark.
Conc.
Corr
U1
U2
U3
U4
U5
U6
U7
U8
U9
U10
U11
U12
U13
U14
U15
16
9
5
21
10
3
25
29
18
1
13
22
4
27
6
RDB23
ESR
IFNG
RF131
TCRa
AMY1
IGF2
COL1A
UPK1
RDB21
OT
GPX
PGY3
PLAT
CASK
59%
45%
94%
54%
50%
50%
54%
60%
43%
45%
76%
73%
54%
53%
28%
.04
−.12
.89
−.11
−.05
−.18
−.04
.13
−.39
−.12
.45
.38
−.04
−.01
−.48
U16
U17
U18
U19
U20
U21
U22
U23
U24
U25
U26
U27
U28
U29
X
11
2
8
15
23, 20
19
7
17
14
27
26
12
24
28
X
POMC
FUCA1
IFNO
CD3e
PL
GMP
INSR
ALDH2
TG
ANT
OAT
F10
MBP
ACTA
DMD
53%
59%
73%
48%
52%
43%
45%
50%
45%
45%
59%
73%
65%
50%
57%
−.07
.09
.42
−.22
−.16
−.28
−.35
−.05
−.18
−.17
−.16
.42
.48
.00
−.08
142
exhibit pigmentation of the ears and/or snout as observed in some
white individuals from the Belgian Blue Cattle breed. Moreover,
mice heterozygous for some mutations at the same loci exhibit
white speckling or interspersed white hairs, yielding a phenotype
referred to as roan. The sterility characterizing most Sl and W
homozygous mutants results from the absence of primordial germ
cells from the gonads. These symptoms, therefore, differ dramatically from the lesions characterizing White Heifer Disease, which
result from the aberrant development of the Müllerian ducts. Interestingly, however, a neutron irradiation-induced mutation—the
cloud-gray mutation—has been described in mice (Kelly 1974),
for which 17 out of 53 analyzed homozygous females and one out
of 66 heterozygous females showed imperforate vaginas, reminiscent of the symptoms observed in White Heifer Disease. As its
name implies, this mutation also has a diluting effect on coat color.
As this mutation did not recombine with the Sl mutations in 98
offspring from double heterozygous mice, it was assumed to be a
new Sl allele (Slcg), although it could as well be a mutation in a
very closely linked gene. While mice homozygous for Sl or W
mutations exhibit severe anemia, in cattle to the best of our knowledge no association has been reported between coat color phenotype and haematopoietic parameters.
The Steel factor is the ligand for the c-kit tyrosine kinase
receptor and is thought to be involved in the migration and/or
differentiation of the melanoblasts (reviewed in Jackson 1994).
The phenotypes associated with the three genotypes at the bovine
roan locus are in reasonable agreement with the expected effects of
a mutation in the Steel gene. Melanoblast migration could be completely impaired in RR animals, resulting in unpigmented hairs. In
r+R animals, a proportion of the hair bulbs would fail to be colonized by melanoblasts. This would imply that the number of melanoblasts originally colonizing the hair bulb is very low, either
generally or more specifically in r+R individuals. Colonization by
a single melanoblast, however, would be sufficient to generate the
number of melanocytes required for full pigmentation of the hair,
explaining why hairs from heterozygous r+R animals are apparently either fully pigmented or completely white.
The availability of the bovine Steel cDNA sequence should
allow us to rapidly test whether this gene cosegregates with the
roan locus and, if this eventually proves to be the case, to look for
causal mutation(s).
Mapping the roan gene is the first step towards its isolation and
characterization, which should shed some light on how a gene
affecting coat color exercises a pleiotropic effect on the development of the Müllerian ducts.
Acknowledgments. The financial support of the Institut pour l’Encouragement de la Recherche Scientifique dans l’Industrie et l’Agriculture (IRSIA)
is greatly acknowledged. We thank Dr. Leif Andersson for stimulating
discussions. We are indepted to Dr. Jay Hetzel, Dr. Alan Teale, and the
BOVMAP consortium for providing us with DNA from the IBRP reference
pedigrees. We are indepted to Prof. J.M. Bienfait, Prof. L. Istasse, and Dr.
I. Dufrasne for their help in generating the Sart-Tilman pedigree.
References
Barendse, W., Armitage, S.M., Kossarek, L.M., Shalom, A., Kirkpatrick,
B.W., Ryan, A.M., Clayton, D., Li, L., Neibergs, H.L., Zhang, N.,
Grosse, W.M., Weiss, J., Creighton, P., McCarthy, R., Ron, M., Teale,
A.J., Fries, R., McGraw, R.A., Moore, S.S., Georges, M., Soller, M.,
Womack, J.E., Hetzel, D.J.S. (1994). A genetic linkage map of the
bovine genome. Nature Genet. 6, 227–235.
Barrington, A., Pearson, K. (1906). On the inheritance of coat color in
cattle. Biometrika 4, 427–464.
C. Charlier et al.: Bovine roan locus and White Heifer Disease
Bishop, M.D., Kappes, S.M., Keele, J.W., Stone, R.T., Senden, S.L.F.,
Hawkins, G.A., Solinas Toldo, S., Fries, R., Grosz, M.D., Yoo, J.,
Beattie, C.S. (1994). A genetic linkage map for cattle. R. (1990).
Brannan, C.I., Bedell, M.A., Resnick, J.L., Eppig, J.J., Handel, M.A.,
Williams, D.E., Lyman, S.D., Donovan, P.J., Jenkins, N.A., Copeland,
N.G. (1992). Developmental abnormalities in Steel (17H) mice result
from a splicing defect in the Steel factor cytoplasmic tail. Genes Dev. 6,
1832–1842.
Charlier, C., Coppieters, W., Farnir, F., Grobet, L., Leroy, P., Michaux, C.,
Mni, M., Schwers, A., Vanmanshoven, P., Hanset, R., Georges, M.
(1995a). The mh gene causing double-muscling in cattle maps to bovine
chromosome 2. Mamm. Genome, in press.
Charlier, C., Belanche, I., Brouwers, B., Coppieter, W., Karim, L., Vanmanshoven, P., Womack, J., Georges, M. (1995b). Mutations in the
MSH receptor underly coat color polymorphism in cattle. In preparation.
Chevalet, C., Carpet, F. (1986). Statistical decision rules concerning synteny or independence between markers. Cytogenet. Cell Genet. 43, 132–
139.
Dietz, A.B., Georges, M., Threadgill, D.W., Womack, J.E., Schuler, L.A.
(1992). Somatic cell mapping, polymorphism, and linkage analysis of
bovine prolactin-related proteins and placental lactogen. Genomics 14,
137–143.
Evvard, J.M., Shearer, P.S., Lindstrom, E.W., Smith, A.D.B. (1930). The
inheritance of color and horns in blue gray cattle. Iowa Agric. Exp. Stn.
Res. Bull. 133, 1–16.
Georges, M., Nielsen, D., Mackinnon, M., Mishra, A., Okimoto, R., Pasquino, A.T., Sargeant, L.S., Sorensen, A., Steele, MR.R., Zhao, X.,
Womack, J.E., Hoeschele, I. (1995). Mapping quantitative trait loci controlling milk production by exploiting progeny testing. Genetics 139,
907–920.
Green, M.C. (1990). Catalog of mutant genes and polymorphic loci. In
Genetic Variants and Strains of the Laboratory Mouse, M.F. Lyon, A.G.
Searle, eds. (Oxford: Oxford University Press), pp. 333–335.
Hanset, R. (1959). L’hérédité des robes dans la race bleu-blanc de
Moyenne et Haute Belgique. Ann. Méd. Vét. 3, 161–188.
Hanset, R. (1969a). Croisements expérimentaux avec des génisses atteintes
de la White Heifer Disease. Ann. Méd. Vét. 113, 3–11.
Hanset, R. (1969b). La White Heifer Disease dans la race bovine de
Moyenne et Haute Belgique: un bilan de dix années. Ann. Méd. Vét.
113, 12–21.
Hanset, R. (1985). Coat colour inheritance in the Belgian White and Blue
cattle breed. Génét. Sél. Evol. 17, 443–458.
Hanset, R. Ansay, M. (1961). La White Heifer Disease: nouvelle description et essai de classification rationnelle de ses différentes formes. Ann.
Méd. Vét. 105, 133–146.
Ibsen, H.L. (1933). Cattle inheritance. Genetics 18, 441–482.
Jackson, I.J. (1994). Molecular and developmental genetics of mouse coat
color. Annu. Rev. Genet. 28, 189–217.
Kelly, E.M. (1974). Mouse News Lett. 50, 52.
Lathrop, M., Lalouel, J.M. (1984). Easy calculations of lodscores and
genetic risk on small computers. Am. J. Hum. Genet. 36, 460–465.
Martin, F.H., Suggs, S.V., Langley, K.E., Lu, H.S., Ting, J., Okino, K.H.,
Morris, C.F., McNiece, I.K., Jacobsen, F.W., Mendiaz, E.A., Birkett,
N.C., Smith, K.A., Johnson, M., Parker, V.P., Flores, J.C., Patel, A.C.,
Fisher, E.F., Erjavec, H.O., Herrera, C.J., Wypych, J., Sachdev, R.K.,
Pope, J.A., Leslie, I., Wen, D., Lin, C.H., Cupples, R.L., Zsebo, K.M.
(1990). Primary structure and functional expression of rat and human
stem cell factor DNAs. Cell 63, 203–211.
Taylor, B.A., Frankel, W.N., Burmeister, M., Bryda, E. (1993). Mouse
Chromosome 10. Mamm. Genome 4 (Suppl.), S154–S163.
Wriedt, C. (1925). Color-sided cattle. J. Hered. 16, 51–56.
Wright, S. (1971). Color inheritance in mammals: cattle. J. Hered. 8, 521–
527.
Zhou, J.-H., Hikono, H., Ohtaki, M., Kubota, T., Sakurai, M. (1994).
Cloning and characterization of cDNAs encoding two normal isoforms
of bovine stem cell factor. Biochim. Biophys. Acta 1223, 148–150.