The Sheep Gene Map
Thomas E. Broad, Diana F. Hill, Jillian F. Maddox,
Grant W. Montgomery, and Frank W. Nicholas
INTRODUCTION
Since their domestication around 7000 to 9000 BC, sheep
have significantly influenced the economic, social, and cultural fabric of human society. The volume entitled "The
Genetics of Sheep," edited by Piper and Ruvinsky (1997),
contains comprehensive reviews of several aspects outlined
in the following brief discussion of the sheep gene map.
Only summary details of these aspects are included below.
Taxonomy
The genus Ovis (Figure 1) comprises several wild and domesticated species (Maijala 1997). This taxonomical usage
is controversial since all of these so-called "species" can
interbreed (Franklin 1997). However, based on chromosome
number, 4 cytogenetic groupings of at least 8 species of sheep
are recognized at the time of this writing:
2n=52
2n=54
2n=56
2n=58
Ovis nivicola (snow sheep or Siberian bighorn)
Ovis aries (domestic sheep)
Ovis canadensis (bighorn)
Ovis dalli (thinhorn or Dall's sheep)
Ovis musimon (European mouflon)
Ovis orientalis (Asiatic mouflon, Urial)
Ovis ammon (Arkhar-Argali, giant wild sheep)
Ovis ammon severtzovi (Severtzov wild sheep)
(Lyapunova and others 1997)
Ovis vignei (Oriental steppe sheep)
The name Ovis aries, which has been given to the domestic sheep apparently to distinguish it from the wild sheep,
is thought to be derived from Ovis orientalis (the Asiatic
mouflon, which may also be the ancestor of the European
mouflon [Maijala 1997]). Of the wild sheep, the thinhorn,
Thomas E. Broad, B.V.Sc. (Hons), M.Sc, Ph.D., is Senior Scientist in the
AgResearch Molecular Biology Unit; Grant W. Montgomery, B.Ag.Sc.
(Hons), Ph.D., is Program Leader of the AgResearch Molecular Biology
Unit; Diana F. Hill, B.Sc, Ph.D., is Director of the Molecular Biology Unit
and Associate Professor in the Department of Biochemistry, University of
Otago, Dunedin, New Zealand. Jillian F. Maddox, B.V.Sc, Ph.D.,
G.Dip.Inf.Sci., is Senior Research Fellow of the Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville,
Australia; and Frank W. Nicholas, B.Ag.Sc, Ph.D., is Associate Professor
in the Department of Animal Science, University of Sydney, Camperdown,
Australia.
160
FIGURE 1 Three medium-wool sheep of the New Zealand Romney breed of the domestic sheep (Ovis aries). Farmed for both wool
and meat production, this breed makes up the majority of the national flock in New Zealand. Ovis aries is 1 of several species of
sheep, which diverged from goats about 5 million yr ago and from
cattle about 25 million yr ago. At the time of this writing, the sheep
gene map is being constructed to identify genes of economic and
medical importance and to understand—through comparisons with
their bovid cousins and more distantly related mammals—how
subtle rearrangements in genome organization result in widely
different biological functions. Photograph reproduced with kind
permission from Wools of New Zealand.
bighorn, and snow sheep have never been domesticated
(Maijala 1997). Most if not all of the gene mapping work has
been, and continues to be, done on various breeds of the
domestic sheep, Ovis aries. For details of these breeds, see
Maijala (1997).
The genus Ovis is one of the 10 genera usually included
in the subfamily Caprinae. A variety of evidence suggests
that Ovis diverged contemporaneously from the goats
(Capra) and chamois (Rupicapra) approximately 5 million
yr ago (Franklin 1997).
The subfamily Caprinae is one of the 9 subfamilies that
comprise the family Bovidae, which includes the subfamily
Bovinae and comprises the bison, buffalo, and wild and domestic cattle. The Caprinae are believed to have diverged
from the Bovinae and other bovid species approximately 17
to 25 million yr ago (Franklin 1997). Robertsonian translocations appear to be common in many of the bovid lineages
and result in the differences in chromosome number between
them. Thus, 3 centric fusion events account for the differences in chromosome number of sheep compared with goats
ILAR Journal
and cattle (2n=60). Apart from a few other minor chromosomal rearrangements, there is a very high level of banding
similarity between the chromosomes of sheep, goats, and
cattle. This similarity has enabled the nomenclature of the
karyotypes of these species to be correlated (Popescu and
others 1996), a development that together with their close
evolutionary relatedness, has been particularly important for
the mapping of the genomes of all 3 genera.
The family Bovidae (cattle, sheep, and goats) is a member of the suborder Ruminantia. The deer also comprise a
large grouping (family Cervidae) of this suborder. These
groupings also have important implications for the mapping
of the sheep genome, as discussed below. (The true ruminants, with 3-chambered stomachs, are classified into the
Pecoran infraorder.) The suborders Ruminantia (deer, cattle,
goats, and sheep), Tylopoda (camelids), and Suiformes (pigs,
peccaries, and hippopotamus) are members of the order Artiodactyla (Franklin 1997). Thus, a relatively close evolutionary relationship can be seen to exist between sheep, goats,
cattle, deer, and pigs.
Genetic Nomenclature
Following the recommendations of the International Society
for Animal Genetics, mapped loci on sheep and other farmed
animal genomes are named using human nomenclature
guidelines. These human guidelines are designed to facilitate
the identification of orthologues in sheep, reflecting the extensive past and current use made of heterologous (particularly human) gene probes and nucleotide sequence data in
the mapping of these genomes. The names and symbols of
human genes can be obtained on the World Wide Web
(Web1) from the Genome Database (http://gdbwww.gdb.org/
gdb/gdbtop.html) and the Human Genome Organization
(HUGO) Genome Database Nomenclature Committee (http:/
/www.gene.uci.ac.uk/nomenclature/). Condensed guidelines
containing rules for homologies with other species have recently been published by White and others (1997).
For all other loci, or those for which no human equivalent was available at the time of preparation, the naming of
sheep loci followed the recommendations of the Committee
on Genetic Nomenclature of Selected Animal Genera
(COGNOSAG1). Recommendations of COGNOSAG are
published in reports of the COGNOSAG Ad Hoc Committee
(1995), Lauvergne and others (1996), and Dolling (1997). In
these guidelines, the nomenclature for the keratins—especially the wool keratins and associated proteins—are from
Powell and Rogers (1994).
'Abbreviations used in this paper: CAB, Center for Animal Biotechnology;
COGNOSAG, Committee on Genetic Nomenclature of Selected Animal
Genera; CSIRO, Commonwealth Scientific and Industrial Research Organization; FAO, Food and Agriculture Organization; FISH, fluorescence in situ
hybridization; IMF, International Mapping Flock; NCL, neuronal ceroid
lipofuscinosis; USDA, US Department of Agriculture; Web, World Wide
Web.
Volume 39, Numbers 2 and 3
1998
REASONS FOR MAPPING THIS SPECIES
As is the case for most species, gene mapping of the sheep is
being performed mainly for the following purposes:
(1) to enhance the quality and diversity of sheep and their
products by positive or negative marker-assisted selection;
(2) to improve animal health and welfare by marker-assisted
selection to eliminate diseases and to protect the environment by reducing the need for widespread use of agrochemicals;
(3) to investigate aspects of speciation and evolution;
(4) to establish models for elucidating the etiology and treatment of human genetic disease; and
(5) to protect genetic diversity and rare breeds and species.
CURRENT MAP STATUS
Maps and associated sheep genome mapping data in the public domain are compiled and available on the Web in
SheepBase (http://zaphod.invermay.cri.nzf). As of December 3, 1997, 627 loci, of which 245 are known genes, have
been mapped in sheep. These loci are graphically displayed
in 2 linkage maps and 1 cytogenetic map, depending on the
method of their mapping. The linkage maps are (1) SMI,
which is a static framework linkage map of Crawford and
others (1995) constructed using the International Mapping
Flock (IMF1) pedigrees; and (2) SMC, a dynamic consensus
sheep linkage map, calculated using SMI as a framework,
containing newly published loci. Included in SMC is a map
of the X chromosome based on the publication of Galloway
and others (1996). The cytogenetic map contains mainly
physically mapped loci. Loci that have been assigned only
to a syntenic group are listed in the Locus Manager of
SheepBase.
The framework linkage map of Crawford and others
(1995) has been updated by a second-generation linkage map
based on the IMF and US Department of Agriculture
(USDA1) Meat Animal Research Center (Clay Center,
Nebraska) pedigrees (De Gortari and others 1998). This map
has 519 markers, including 504 microsatellites of which 74%
have also been mapped in cattle, and a total autosomal length
of 3063 cM. Work is under way to install it in SheepBase
where it will be displayed together with the first-generation
framework map of Crawford and others (1995).
A third-generation autosomal linkage map with an estimated length of 3492 cM is presently under construction at
the time of this writing (Dr. Jill Maddox, Centre for Animal
Biotechnology (CAB1), University of Melbourne, personal
communication, 1998). Based on and extending the firstand second-generation maps (see above), the CAB map is
3270 cM long. A list of markers that are included in the
third-generation map and CAB map is presently accessible
on the Web at http://rubens.its.unimelb.edu.au/~jillm/
JILL.HTM. Comparative data on the relative lengths of each
161
of the autosomes in the CAB second- and third-generation
maps and the numbers of markers mapped on each autosome
are also available at this site. The third-generation map gives
an average coverage of 4.2 cM between markers on the sheep
genome except for regions missing from ends of chromosomes as deduced from comparisons among cattle and sheep
maps (Table 1) and regions of the sheep map with gaps
greater than 20 cM as deduced from comparisons among
cattle and sheep maps (Table 2).
APPROACHES USED TO DEVELOP
THE MAP
Physical (cytogenetic) and genetic (linkage) mapping procedures constitute the main mapping approaches for sheep.
Both have been reviewed (Broad and others 1997; Montgomery and Crawford 1997).
Physical Mapping
Several attempts have been made since 1976 to produce a
globally accepted standard karyotype for the sheep (Ansari
and others 1994). Agreement was reached in Texas in 1995
for a standard sheep karyotype that was correlated with the
cattle standard on the basis of similar banding patterns and
gene loci (Broad and others 1997). The G-/Q- and R-banded
idiograms of Ansari and others (1996), derived from sequentially Q- to G-banded and Q- to R-banded metaphase spreads,
are fully consistent with the 1995 (Texas) standard sheep
TABLE 1 Regions of the third-generation ovine map
lacking markers at the ends of sheep chromosomes
Chromosome
Region
Distance (cM)
4
5
12
13
18
Top (cen): BMC1410
Top (cen):TGLA176
Top (cen): BMS357
HUJ625: bottom
Top (cen): BM8115
8
14
8
7
17
karyotype. These karyotypes were constructed by conventional cytogenetic procedures from sheep with 3 different
Robertsonian chromosomes that served as morphological
markers. Nucleolar organizer chromosomes were used as
cytological markers.
At the lowest level of resolution, loci may be mapped to
individual chromosomes by analysis of somatic cell hybrids.
A cytogenetically characterized panel of 30 sheep-hamster
cell hybrids representing the complete sheep genome has
been produced for this purpose (Burkin and others 1997a).
Alternatively, mapping to synteny groups (which have now
been assigned to specific ovine chromosomes) can be performed using the panel of hamster-sheep cell hybrids developed by Saidi-Mehtar, Hors Cayla, and colleagues (ImamGhali and others 1991). The production of individually
flow-sorted sheep chromosomes (Burkin and others 1997b)
complements these cell hybrids as an additional resource for
assigning loci to sheep chromosomes.
At a higher level of resolution, loci may be assigned to
subchromosomal regions by in situ hybridization using isotopically or fluorescently labeled probes (reviewed in Broad
and others 1997). Whereas the level of resolution achievable
by fluorescence in situ hybridization (FISH1) on metaphase
or premetaphase chromosomes is generally recognized to be
about 1% of the length of the genome, considerably higher
resolution (to between 200 and 300 kb) can be obtained using fiber FISH (Mann and others 1997).
Beyond this chromosomal level of resolution, physical
mapping is performed by molecular techniques using a sheep
yeast artificial chromosome library with an average insert
size of approximately 650 kb (Broom and Hill 1994), and a
sheep bacterial artificial chromosomal library with an average insert length of 100 kb (C. Bottema, University of
Adelaide, Waite Campus, South Australia, personal communication, 1998). Cosmid and plasmid libraries of the sheep
genome have been constructed in commercial laboratories
such as Clontech and various research institutions (including
AgResearch in New Zealand; CAB, Commonwealth Scientific and Industrial Research Organization (CSIRO), and
Howard Florey in Australia; and Basel Institute for Immunology in Switzerland). Specific libraries may be available
on request from particular laboratories.
Linkage Mapping
TABLE 2 Regions of the sheep genome without
markers in the third-generation ovine map
Chromosome
7
8
11
13
21
23
162
Region
Distance (cM)
BM3033:BM1237
INRA127:McMA5
MAP2C: CSSM08
BM9202: BMS745
BL42: BMS995
McM541L:McM135
McM136: URB031
22
36
-25
25
>40
39
28
Laboratories in New Zealand, Australia, and the United
States have collaborated to develop the sheep linkage map
using a common set of reference pedigrees. The first linkage
map was published in 1995 using the AgResearch International Mapping Flock (IMF, Crawford and others 1995). The
map contained 232 markers covering 2070 cM with an average distance of 14.4 cM between markers (Crawford and
others 1995). This map represented approximately 75% coverage of the sheep autosomes.
The IMF flock, on which this first map was based, comprises 9 3-generation full-sib pedigrees with 222 informaILAR Journal
tive meioses. DNA from these families has been distributed
to 14 laboratories worldwide. Subsequently, additional
families were developed by the USDA at Clay Center, Nebraska (De Gortari and others 1998). These families consist
of 247 backcross progeny from mating 4 Fl Romanov-cross
rams to Romanov ewes The combined set of reference
pedigrees was used for the second-generation linkage map
(De Gortari and others 1998). This map containing 519
markers increases the coverage of the map by approximately
1000 cM and consolidates all of the linkage groups into 1
per chromosome. A third set of sheep mapping pedigrees
has been developed by CSIRO and comprises 15 3-generation full-sib families of 182 progeny produced by mating 2
Romney rams carrying the tj and t2 Robertsonian translocations with 9 fine-wool Merino ewes carrying the Booroola
fecundity gene. The largest of these families has 29 offspring. Combined with the other flocks, this is the basis of
the third-generation map (see above) of 3492 cM comprising 829 markers.
An important feature of the sheep linkage map has been
the extensive use of cattle microsatellite markers, which
greatly facilitates the comparison of the ovine and bovine
maps. Approximately 50% of bovine microsatellite primer
pairs amplify informative markers in sheep (De Gortari and
others 1997): 402 (80%) of the linked microsatellites in the
second-generation sheep map are bovine primer pairs, and
553 (67%) in the third-generation map are bovine in origin.
The ovine and bovine maps show extensive conservation of
marker order within linkage groups, with some exceptions.
One such exception is sheep chromosome 9 whose proximal region appears to have been translocated from the
subtelomeric end of cattle chromosome 9 to fuse with cattle
chromosome 14, which has conserved linkage with the remainder of sheep chromosome 9 (Crawford and others
1995). An equivalent translocation event is observed in
goats (Vaiman and others 1996).
In addition to the reference families used for the framework maps, several groups are mapping in resource families
(see below) as part of searches to identify quantitative trait
loci or for positional cloning projects. A map of sheep chromosome 6 was developed using the IMF pedigrees together
with families segregating for the Booroola fecundity gene
(Lord and others 1996). A map of the sheep X chromosome
with 14 markers and 7 genes was reported by Galloway and
others (1996). A detailed map of the distal region of sheep
chromosome 18, which harbors the Callipyge gene, has been
reported by Cockett and others (1996).
Although the large majority of markers are microsatellites,
other categories of markers are single-strand conformation
polymorphisms, restriction fragment length polymorphisms,
minisatellites, and protein polymorphisms (Montgomery and
Crawford 1997). Random-amplified polymorphisms have
been developed and mapped by Cushwa and others (1996);
and more recently, amplified fragment length polymorphism
markers have also been mapped in sheep (J. Lumsden,
AgResearch Molecular Biology Unit, Dunedin, New Zealand,
personal communication, 1998).
Volume 39, Numbers 2 and 3
1998
AVAILABLE FLOCKS FOR MAPPING
Reference Flocks
Three flocks have been generated specifically for mapping
(see above also): (1) IMF, comprising 9 pedigrees each of 3
generations (Crawford and others 1995); (2) the CSIRO
mapping flock of 15 3-generation full-sib families (Dr. Beryl
van Hest, CSIRO Prospect, NSW, Australia, personal communication, 1998); and (3) the USDA Meat Animal Research Center Clay Center flock (De Gortari and others
1998). DNA from these flocks is available on request for
mapping purposes. The widespread use of these flocks (particularly the IMF early on) by the sheep genome mapping
community has been instrumental in coordinating the global
development of a single major map for the species.
Resource Flocks
The wealth of material generated in both single and quantitative trait loci selection lines for genetic studies may also be
of value in genetic studies in other species. Because of the
potential comparative benefit of this material, we briefly list
and describe this material below. However, it should be
noted that this compilation is not comprehensive.
Disease-resistant Flocks
Parasite resistance. Eight independent lines of sheep
have been selected in New Zealand and Australia for resistance and susceptibility to internal parasites (see Morris
1998). In New Zealand, gene mapping studies have focused
primarily on divergent fecal egg count lines of Romney sheep
that have now diverged by a population standard deviation of
2.6. Rams produced by reciprocal crosses between these
lines have been outcrossed to unselected Coopworth ewes,
and the progeny that exhibit variation in their resistance to
parasites (from susceptible to tolerant/resistant) are being
genotyped using a full genomic scan (Crawford and others
1997a). Work is under way to genotype a Haemonchus selection flock between Dr. Jill Maddox of Melbourne University, Melbourne, Australia, and Dr. Jim Miller of Louisiana
State University, Baton Rouge, Louisiana.
Facial eczema. Facial eczema is a mycotoxicosis
caused by the ingestion of the hepatotoxin sporedesmin
produced by the fungus Pithomyces chartarum, which
lives on rye grass litter in pasture. Since 1975, resistant
and susceptible lines of Romney sheep have been bred
while being monitored by the serum concentrations of the
hepatic enzyme gamma glutamyl transpeptidase after oral
administration of the toxin. The lines have now diverged
by 2.3 standard deviations (Morris and others 1995b).
The selection lines were crossed in 1992, and 4 Fl rams
were outcrossed to unselected Romney ewes. The resulting progeny are being genotyped using both a candidate
163
gene and genomic scan approach (Crawford and others
1997b).
Rye grass staggers. The toxin lolitrem B of an endophytic fungus in rye grass produces rye grass staggers. A
genetic correlation of 0.3 has been found between this condition and facial eczema, suggesting possible common pathways of detoxification. Based on natural challenge, selection
lines in Romney sheep established since 1993 show a divergence of 0.8 phenotypic standard deviations (Morris and others 1995a). Genotypic analysis is presently limited to the
investigation of candidate genes from the facial eczema study.
Footrot. Morris (1998) lists heritability estimates in
Australian Merino and New Zealand Romney sheep for susceptibility to footrot, a disease produced by the bacterium
Dichelobacter nodosus. Selection lines were established in
Australian Merinos in 1993 (Raadsma and others 1996).
Candidate genes are being tested in half-sib families that
have been scored for clinical and antibody response to infection and vaccination.
Medical Models
Cystic fibrosis. A DNA variant has been found of the
ovine cystic fibrosis transmembrane conductance regulator
(CFTR) gene that was previously reported as a putative mutation causing cystic fibrosis in humans (Tebbutt and others
1996). Using multiple ovulation-embryo transfer techniques,
a ram lamb carrying this mutation in the homozygous state
has been produced and will be used to generate progeny for
subsequent clinical and genetic investigation. The advantages of an ovine model for cystic fibrosis have been discussed by Harris (1997).
Batten disease/neuronal ceroid lipofuscinosis (NCL1):
Batten disease is the most common of the neuronal ceroid
lipofuscinoses. An ovine form of this storage disorder, which
results in progressive neuronal degeneration and leads to
blindness, deafness, and death, has been extensively characterized by Jolly and colleagues (1992) in South Hampshire
sheep in New Zealand. Although a small nucleus flock of
affected animals is maintained, a substantial archive of more
than 300 DNA samples from 60 pedigrees has been established and is being used to genetically characterize the disease, initially by gene mapping. In humans, at least 6 variants of NCL have been described. The genes for only 3 of
these are known at the time of this writing, but mapping has
excluded them from involvement in the ovine NCL (Dr. M.
Broom, Molecular Biology Unit, Biochemistry Department,
University of Otago, Dunedin, New Zealand, personal communication, 1998). Analysis of regions of the genome harboring the other variants is under way at the time of this
writing.
Congenital cataract. Sheep with congenital cataract
were identified by Dr. R. D. Jolly, Department of Veterinary
Pathology and Public Health, Massey University, Palmerston
North, New Zealand. At the time of this writing, 3 carrier
rams descended from these animals are being mated to un164
selected ewes at AgResearch Invermay, Mosgiel, New Zealand, to generate a nucleus flock in which the affected gene is
segregating.
Noneruption of incisor teeth. It appears that a recessive
gene originating in a carrier ram in an unselected line of
Coopworth sheep (Broad and others 1996) results in noneruption of incisor teeth and leads to death after weaning. At
the time of this writing, a nucleus flock harboring the gene is
being established for subsequent candidate gene and clinical
investigation.
Inherited deafness. Sheep obtained from at least 3 independent flocks have been demonstrated by electrophysiology testing to be profoundly deaf. Breeding of affected individuals is under way for candidate gene studies.
Chromosome translocation flocks. Nucleus flocks are
being maintained of sheep carrying the following Robertsonian translocations: t, {rob 6;24), t2 {rob 9; 10), t3 {rob
7;25), and t5 {rob 8; 22) (Ansari and others 1993; Pearce and
others 1994). Sheep with the first 3 of these centric fusions
are derived from those initially detected by Bruere and others (1974) in New Zealand Romney sheep. All except the
last are maintained in a homozygous state, and a flock carrying multiple translocations has been established in which the
2n chromosome number of several animals is 48.
Body Composition Traits
Backfat. Beginning in 1981, high (fat), low (lean), and
control lines of Coopworth sheep were established at
Invermay based on ultrasonic fat depth scans over the last
rib, corrected for body weight. In birth years 1991 and
1992—the last 2 yr of selection—the fat and lean lines had
diverged 2.08 and —0.85 mm in fat depth from the control
line (equivalent to +2.50 and -1.03 phenotypic standard deviations, respectively). Large responses were recorded in
live weight between the lines, with the fat and lean lines
averaging 34.0 and 40.2 kg compared with 38.0 kg for the
controls (Morris and others 1997). In 1993, the fat and lean
lines were crossed: Fl rams were subsequently backcrossed
with both selection lines in 1995 and 1996 (Jopson and others 1998). At the time of this writing, progeny born from
these reciprocal backcrosses are being subjected to candidate
gene genotypic analyses. High and low backfat Southdown
selection lines of sheep were also established in 1979 (Carter
and others 1989), but these have been the subject of limited
physiological analyses.
Glucose clearance. A nucleus is being maintained of a
flock of Coopworth sheep that were selected on the basis of
the plasma clearance of a bolus intravenously injected dose of
glucose. There was an initial but no subsequent divergence of
the selection lines, with the slow-clearance line having a 3%
higher basal plasma glucose level than the control line and the
fast line 10% lower than the controls. The fast-clearance line
had higher plasma insulin levels during the test and 11 % more
subcutaneous fat at the same carcass weight than the slowclearance line (Francis and others 1994).
ILAR Journal
A recessive pigmentation gene suspected to be a homologue of the mouse agouti gene has been reported in the
progeny derived from a "self color" grandsire crossed to
white dams and subsequently backcrossed to self-color ewes
(Parsons and others 1997).
Muscling. The Callipyge gene, which produces muscular hyperplasia in sheep (particularly of the hindquarters),
has been mapped to the distal region of sheep chromosome
18. Only the paternally inherited copy of Callipyge appears
to be expressed (Cockett and others 1996). The gene was
first detected in a ram called "Solid Gold" in a commercial
Dorset flock in Oklahoma and was subsequently found to
transmit the unusual phenotype to its descendants. Several
flocks containing the gene have now been established in the
United States, Canada, and Europe. Work is under way to
identify the gene by positional cloning.
The Carwell locus, which increases the size of the ribeye (longissimus dorsi) muscle in sheep, has been detected in
the progeny of rams derived from the Carwell Poll Dorset
stud, Armidale, NSW, Australia (Nicoll and others 1998).
The Carwell locus maps to a similar region of sheep chromosome 18 as the Callipyge gene. Work is under way to study
the inheritance of the locus in commercial synthetic flock of
sheep (Nicoll and others 1997) and to determine whether it is
allelic to Callipyge.
Milk and meat traits. In 1995, Raadsma and Nicholas
at the University of Sydney began the establishment of a
resource flock for milk, fleece, and meat traits by crossing
Awassi rams with finewool Merino ewes. Backcross progeny are being scored for the widest possible range of traits:
Female progeny are being recorded for all the important milk
yield and composition traits throughout a lactation; male
progeny are being scored for food intake, growth, and meat
quality traits; and all progeny are being recorded for a wide
range of scoreable traits including coat color, breed type, and
tail length. All progeny are also being subjected to a genome
scan with 150 markers.
The Booroola fecundity gene appears to have arisen de novo
in the "Booroola" Merino commercial flock in which the
Seears brothers in Australia selected to increase its frequency.
By 1980, it was regarded as a single autosomal mutation, and
it is now known to increase litter size by 1 lamb per gene
copy due to an additive effect on ovulation rate. The gene
has subsequently been mapped to sheep chromosome 6 using
a whole genome scanning approach (reviewed in Montgomery and others 1994), and work is under way to find more
closely linked markers and to isolate the gene by positional
cloning methods.
The Inverdale prolificacy gene was first discovered in
1984 in a prolific family of Romney sheep that descended
from 1 ewe. Progeny testing of her male descendants carried
out from 1985 to 1990 indicated the presence of the Inverdale
fecundity gene on the X chromosome. One copy of the gene
increased ovulation rate by about 1.0 and litter size by about
0.6. However, in 1991 it was found that ewes with 2 copies
of the gene have small nonfunctional "streak" ovaries and
are infertile. Then in 1993, the gene was found in a second
independent prolific flock of Romney sheep (Davis and others 1995). Mapping is under way to find markers linked to
the gene (Galloway and others 1995, 1996).
Wool Traits
SCIENTIFIC CONTRIBUTIONS OF THE MAP
Ultrafine Merino rams were mated in 1991 with high fleece
weight-selected Romney ewes to generate Fl rams that were
mated over 2 yr with Merino ewes to generate backcross
progeny. A similar series of matings was performed with
Romney ewes to produce reciprocal backcross progeny.
Genomic scans are being performed to detect linkage with
the following wool traits: fleece weight, fiber diameter,
medullation, staple strength, staple length, fiber crimp,
brightness, yellowness, bulk, and resilience (Wuliji and others 1995). A similar study involving genome scans is under
way in Victoria, Australia, using a wool-trait selection flock
generated from rams derived from superfine Merino
grandsires mated with Border Leicester and strong-wool
Merino ewes that were backcrossed to strong-wool Merino
ewes to produce large family groups each containing at least
100 animals (Ward and others 1995).
Candidate gene studies are under way at the time of this
writing for wool production and wool quality traits in animals of the CSIRO mapping flock (described in detail above).
Material from this flock is available on request from Dr.
Beryl van Hest, CSIRO, Prospect, NSW, Australia.
Mapping Successes
Volume 39, Numbers 2 and 3
1998
Fecundity Traits
Genetic maps and markers are being applied in sheep to
problems of parentage and individual identification, mapping genes affecting production, and studies of evolution.
Markers have been used to check the accuracy of pedigree
records (Crawford and others 1993) and to confirm the origin of offspring after cloning by nuclear transfer (Campbell
and others 1996). The number of loci with phenotypic effects that have been mapped to specific locations is increasing (Table 3). Loci include those affecting carcass traits,
milk production, ovulation rate, litter size, wool quality, and
fleece weight. These traits have been mapped using a combination of candidate gene studies and genome scans.
Although not yet published at the time of this writing, a
point mutation has been found (Beever and others 1998) in
the fibroblast growth factor 3 receptor gene for spider lamb
syndrome, which results in the excessive development of
cartilage leading to bone deformities (Lauvergne and others
1996). Use of this genetic knowledge, and of the markers
linked to these traits, is expected to contribute to the devel165
TABLE 3 Single gene and quantitative trait loci associations reported for sheep
Trait
Locus
Carcass traits
Adipocyte fatty acid binding protein
Carcass traits
Lipoprotein lipase
Muscular hypertrophy
Callipyge
Hypertrophy of L dorsi muscle
Carwell
Milk production
Growth hormone
Milk production
OarJMP8
Booroola fecundity gene
Prolificacy
Prolificacy
Inverdale fecundity gene
Ovulation rate
Hemoglobin beta
Wool fiber diameter
Fibroblast growth factor 1
Wool fiber diameter
Keratin-associated protein 6
Wool fleece weight
Fibroblast growth factor 1
Wool strength
Keratin gene complex
Horns
Horns
J
NI, ovine chromosome not identified at the time of this writing.
opment of marker-assisted selection procedures to accelerate
the genetic improvement of sheep. This subject has been
reviewed by Montgomery and Kinghorn (1997).
Comparison with Other Genomes
The locations of 220 known genes on the sheep genome have
been compared with their counterparts in cattle, pig, human,
and mouse (Broad 1997). Displays of these data in Oxford
grids illustrate the extent of conservation of chromosomal
organization (conserved synteny) among these species—
greatest with cattle and least with mouse. Thus, there is a
one-to-one correspondence between chromosomes and chromosomal arms of the sheep and cattle genomes but increasing fragmentation compared with human and mouse, respectively. A total of 40 conserved chromosomal segments have
been identified to date between sheep and human, and 55
between sheep and mouse.
There is also a high level of conserved synteny between
the sheep and deer genomes (see below). Unlike comparisons of sheep with human and mouse, this conservation appears to extend to conserved linkage, that is, where the relative order of loci within these conserved segments is also
conserved (Broom and others 1996). Thus the deer map may
be useful in fine-mapping the sheep and possibly other artiodactyl or ruminant genomes.
ANTICIPATED FUTURE CONTRIBUTIONS
OF THE MAP
Chromosome
Reference
Nla
2
18
18
11
6
6
X
15
Nl
1
Nl
11
10
Cockett and Medrano (1996)
Cockett and Medrano (1996)
Cockett and others (1996)
Nicoll and others (1998)
Gootwine and Ofir (1996)
Diez Tascon and others (1996)
Montgomery and others (1994)
Davis and others (1995)
Glazkoand others (1997)
Robinson and others (1995)
Parsons and others (1994)
Robinson and others (1995)
Rogers and others (1994)
Montgomery and others (1996)
Pere David's deer x red deer hybrids (Tate and others 1997a).
At the time of this writing, the deer map contains 251 mapped
loci, of which 145 are mapped in human, 93 in sheep, and 113
in cattle. Comparison of the relative order of these loci in the
different species has revealed very few rearrangements between sheep, cattle, and deer. However, comparison of the
deer and human maps reveals considerable evidence for conserved synteny but not conserved linkage. Thus, for ruminants, the availability of the deer interspecies mapping panel
provides an invaluable resource for mapping and ordering loci
across a wide range of species (Tate and others 1997b).
It would be both novel and useful if the deer map became
the generic map for ruminants such as sheep, goats, and
cattle. Two main uses for it are immediately apparent: for
efficiently establishing the order of loci within regions of
conserved synteny and for efficiently mapping type I loci
(known genes and expressed sequence tags) from other species precisely onto the ruminant chromosomes. In the context of this review, the latter application has great appeal
since the availability of the deer interspecies mapping panel
overcomes 2 important comparative mapping bottlenecks:
marker heterozygosity and integration of new mapping data
with existing physical and linkage mapping information. In
the deer panel, variation can be readily demonstrated in most
markers (saving considerable time and expense). In addition, using breakpoint mapping analysis, most syntenic markers can be rapidly ordered relative to each other or, at worst,
grouped into "bins" of adjacent markers. This process facilitates the extrapolation of mapping information from human
and mouse and other species into the ruminants and will
accelerate positional cloning studies.
Generation of a Generic Ruminant Map
Sheep Models of Human Genetic Diseases
An interspecies deer hybrid mapping panel has been generated
from 346 1/4 Pere David's deer (Elaphurus davidianus): 3/4
red deer (Cervus elaphus) backcross progeny from male Fl
166
Although the relevance of any animal model depends on
anatomical, physiological, and genetic similarity to the huILAR Journal
man disorder, sheep have several general advantages over
mice and other laboratory animals as potential models for the
study of human diseases and metabolic disorders. Physically, sheep are similar in size to human subjects, facilitating
the development of new surgical procedures and the testing
of therapeutic agents. Phylogenetically, sheep are more
closely related to humans than are mice and other rodents.
On some cultural and religious grounds, there are fewer restrictions to using sheep than pigs. In countries such as New
Zealand and Australia, the cost of sheep is substantially lower
than in Europe and many other regions. These comparative
advantages have contributed to the development of ovine
models for several human disorders (see below). Nicholas
(1997) has listed 36 traits and inherited disorders in sheep
that may be potential models for human disorders.
Conservation Biology
Mapped microsatellite markers have been used to determine
evolutionary relationships between sheep breeds (Buchanan
and others 1994) and parentage in wild populations such as
Soays (Gulland and others 1993) and Rocky Mountain Bighorns (Forbes and others 1995). The sheep genome map and
its associated resources can be used to help in the conservation of sheep breeds. It has been estimated that 148 breeds of
sheep have become extinct in the last 100 yr (see Ponzoni
1997).
The issue of genetic resources conservation is becoming
increasingly acute for sheep as well as for all other biota. For
a comprehensive review of this area as it concerns sheep, see
Ponzoni (1997). For information on the United Nations Food
and Agriculture Organization (FAO) global program for management of farm animal genetic resources, see the FAO Web
site (http://dad.fao.org/dad-is/library'/programm/index.htm).
As part of this developing global initiative, an expert committee is making recommendations for a panel of microsatellite
markers to assist in identifying sheep breeds at risk of extinction by measuring the relative diversity of the existing breeds.
At the time of this writing, the large Domestic Animal Diversity Information System (DAD-IS) database of relevant Web
information has moved from the design to the implementation
phase (http://dad.fao.org/dad-is/index.htm).
Fundamental Science
As the pace of gene mapping increases in sheep and in other
species, evolutionary break points may be characterized that
will help us understand the events associated with speciation. The sites of meiotic breakpoints may also be dissected
and may assist in defining, or even manipulating, mechanisms of chromosome rearrangement. Ultimately, this information on chromosome structure and organization may lead
to a more thorough understanding of gene expression, which
may in turn result in the development of novel methods to
control patterns of growth and development.
Volume 39, Numbers 2 and 3
1998
USES OF THE MAP AND ACCESSIBILITY
SheepBase
SheepBase is a database of publicly available, updated mapping information and associated data that are accessible on
the Web (http://zaphod.invermay.cri.nzf). The primary site
of SheepBase is AgResearch Invermay, Mosgiel, New
Zealand; secondary nodes are available at the Roslin Institute, Edinburgh (http://www.ri.bbsrc.ac.uk/sheepmap/), and
at the US National Agricultural Library, Beltsville, Maryland (http://tetra.gig. usda.gov: 8400/).
The software platform for SheepBase is ARKdb, the
same as that for PigBase, ChickBase, and BovBase. This
platform—Anubis, the graphical map display, and the Web
interface—were developed by Chris Mungall and Dr. Jian
Hu of the Roslin Institute, Edinburgh, and Dr. Alan Hillyard,
formerly of the Jackson Laboratory, Maine. SheepBase initially used the GBASE (mouse) database developed by Jackson Laboratory. ARKdb has been designed as a generic
single-species genome database. It is hoped that its adoption
by an increasing number of species mapping groups will
establish a common foundation that will facilitate betweengenome comparisons.
In the new ARKdb platform, the stored information includes chromosomal locations and relative positions (where
reported) of loci, full reference citations, and details of DNA
polymorphisms, clones, and probes. The addition of links to
other databases is planned.
Other Useful Sheep Databases
A wealth of sheep genome data organized, collated, and
annotated by Frank Nicholas and colleagues (University of
Sydney, NSW, Australia) is now available on the Web at
the Australian National Genome Information Service
(http://www.angis.su.oz.au). Based on McKusick's online
database of human disorders entitled Mendelian Inheritance in Man
(http://www3.ncbi.nlm.nih.gov/omim/),
Nicholas has created Mendelian Inheritance of Animals
(MIA) online at the Web address http://angis.su.oz.au/Databases/BIRX/omia/, where more than 139 ovine traits and
disorders are listed together with a complete list of references. Some of this material has been published (Nicholas
1997).
Also online at the same address are the
COGNOSAG catalogs of loci, which have been published
under the title Mendelian Inheritance in Sheep MIS96
(Lauvergne and others 1996). In the database entitled
Online Chromosomes of Animals, Nicholas has also made
available a complete bibliography of sheep and other animal karyotypes.
At the CAB Web site (http://rubens.its.unimelb.edu.au/
-jillm/JILLHTM), Jillian Maddox has made available her
compilations of detailed comparative mapping data of sheep
and other mammals in addition to reports of Australasian
linkage mapping meetings.
167
CONCLUSION
Coordination of Action
Sheep genome research is being pursued actively in many
countries around the world at the time of this writing;
however, no formal mechanism exists to coordinate this
effort. Research findings are widely communicated in a
broad range of scientific journals and at equally diverse
conferences, workshops, and other forums. In addition,
a national sheep mapping program entitled SheepMap™
has been established in New Zealand. For full details,
click on http:// agresearch.cri.nz and http://biochem.
otago.ac.nz:800/panzora/mbu/mbu3.html. In the United
States, the sheep genome initiative is coordinated by Professor Noelle Cockett, Utah State University, Logan,
Utah, under the US Department of Agriculture National
Animal Research Program.
Future Perspectives
Although funded relatively modestly compared with cattle and
pig genome programs, the sheep genome mapping initiative
has already contributed substantially to knowledge of the organization and evolution of the vertebrate genome and has laid
solid foundations for developing a better understanding of the
genetic basis of the biology of the sheep. As more detailed
investigations proceed in the future of those regions of the
sheep genome that are shown to be important economically to
the sheep industry or medically to human health, there will be
increasing opportunity for comparisons with the genomes of
other species. These finely mapped regions of the sheep genome will, of necessity, be rich in information about the coding regions and other landmark loci and of the spatial organization and distances between these loci. Data such as these
will provide the substance rather than the flavor of comparative genome analyses. For this we are all impatient!
ACKNOWLEDGMENTS
We gratefully acknowledge Dr. A. L. Archibald, C. Mungall,
Dr. Jian Hu, and colleagues of the Roslin Institute,
Edinburgh, for making the software platform ARKdb available to us and for their help in establishing SheepBase. The
work of T. E. B., D. F. H., and G. W. M. was funded as part
of a program grant to AgResearch from the New Zealand
Foundation for Research, Science and Technology. J. F.
M.'s work was funded as part of a grant for the Australian
Meat Research and Development Council.
REFERENCES
Ansari HA, Bosma AA, Bunch TD, Long SE, Popescu CP. 1994. Clarification of chromosome nomenclature in the sheep (Ovis aries). Report of
168
the committee for the standardization of the sheep karyotype. Cytogenet
Cell Genet 67:114-115.
Ansari HA, Maher DW, Pearce PD, Broad TE. 1996. Resolving ambiguities in the karyotype of the domestic sheep (Ovis aries). II. G-, Q-, and
R-banded idiogram and chromosome-specific molecular markers. Chromosoma 105:62-67.
Ansari HA, Pearce PD, Maher DW, Malcolm AA, Broad TE. 1993. Resolving ambiguities in the karyotype of domestic sheep (Ovis aries). Chromosoma 102:340-347.
Beever JE, Meyers SN, Shay TL, Stephens A, Cockett ME. 1998. Spider
lamb syndrome is caused by a point mutation in ovine fibroblast growth
factor receptor 3 (FGFR3). Proc 26th Int Conf Anim Genet, Auckland,
New Zealand (Abstract D02).
Broad TE. 1997. Mapping the sheep genome: Current status and comparison with other species (June 1997). AgBiotech News Infor 9:297N3O8N.
Broad TE, Hayes H, Long SE. 1997. Cytogenetics: Physical chromosome
maps. In: Piper L, Ruvinsky A, editors. The Genetics of Sheep. New
York: CAB International, p 241-295.
Broad TE, Jopson NB, McEwan JC. 1996. Non-eruption of lower incisor
teeth in sheep. Proc NZ Genet Soc Queentown (Abstract).
Broom JE, Tate ML, Dodds KG. 1996. Linkage mapping in sheep and
deer identifies a conserved pecora ruminant linkage group orthologous
to two regions of HSA16 and a portion of HSA7q. Genomics 33:358364.
Broom MF, Hill DF. 1994. Construction of a large-insert yeast artificial
chromosome library from sheep DNA. Mamm Genome 5:817-819.
Bruere AN, Zartman DL, Chapman HM. 1974. The significance of the Gbands and C-bands of the three different Robertsonian translocations of
domestic sheep (Ovis aries). Cytogenet Cell Genet 13:479-488.
Buchanan FC, Adams LJ, Littlejohn RP, Maddox JF, Crawford AM. 1994.
Determination of evolutionary relationships among sheep breeds using
microsatellites. Genomics 22:397-403.
Burkin DJ, Broad TE, Lambeth MR, Burkin HR, Jones C. 1997a. New gene
assignments using a complete, characterized sheep-hamster somatic cell
hybrid panel. Anim Genet 29:1-7.
Burkin DJ, O'Brien PCM, Broad TE, Hill DF, Jones CA, Wienberg J,
Ferguson-Smith MA. 1997b. Isolation of chromosome-specific paints
from high-resolution flow karyotypes of the sheep (Ovis aries). Chromosome Res 5:102-108.
Campbell KHS, Me Whir J, Ritchie WA, Wilmut I. 1996. Sheep cloned by
nuclear transfer from a cultured cell line. Nature 380:64-66.
Carter ML, McCutcheon SN, Purchas RW. 1989. Plasma metabolite and
hormone concentrations as predictors of genetic merit for lean meat
production in sheep: Effects of metabolic challenges and fasting. NZ J
Agric Res 32:343-353.
Cockett NE, Jackson SP, Shay TL, Fanir F, Berghams S, Snowder GD,
Nielsen DM, Georges M. 1996. Polar overdominance at the ovine
callipyge locus. Science 273:236-238.
Cockett NE, Medrano J. 1996. Development and use of the sheep genome
map. In: Miller RH, Pursel VG, Norman HD, editors. Beltsville Symposia in Agricultural Research XX: Biotechnology's Role in Genetic
Improvement of Farm Animals. Savoy, IL: American Society of Animal Science, p 81-90.
COGNOSAG [Committee on Genetic Nomenclature of Selected Animal
Genera] Ad Hoc Committee. 1995. Revised guidelines for gene nomenclature in ruminants 1993. Genet Sel Evol 27:89-93.
Crawford AM, Dodds KG, Ede AJ, Pierson CA, Montgomery GW, Garmonsway HG, Beattie AE, Davies K, Maddox JF, Kappes SW, Stone
RW, Nguyen TC, Penty JM, Lord EA, Broom JE, Buitkamp J, Schwaiger
W, Epplen JT, Matthew P, Matthews ME, Beh KJ, Hill DF. 1995. An
autosomal genetic linkage map of the sheep genome. Genetics 140:703724.
Crawford, AM, McEwan JC, Dodds KG, Bisset SA, Macdonald PA, Knowler KJ, Greer GJ, Green RS, Cuthbertson RP, Wright CS, Vlassoff A,
Squire DR, West CJ, Paterson KA, Phua SH. 1997a. Parasite resistance:
A genome scan approach to finding markers and genes. Proc NZ Soc
Anim Prod 57:297-300.
ILAR Journal
Crawford AM, Phua SH, McEwan JC, Dodds KG, Wright CC, Morris CA,
Bisset SA, Green RS. 1997b. Finding disease resistance QTL in sheep.
Anim Biotech 8:13-22.
Crawford AM, Tate ML, McEwan JC, Kumaramanickavel G, McEwan
KM, Dodds KG, Swarbrick PA, Thompson P. 1993. How reliable are
sheep pedigrees? Proc NZ Soc Anim Prod 53:363-366.
Cushwa WT, Dodds KG, Crawford AM, Medrano JF. 1996. Identification
and genetic mapping of random amplified polymorphic DNA (RAPD)
markers to the sheep genome. Mamm Genome 7:580-585.
Davis GH, McEwan JC, Fennessy PF, Dodds KG. 1995. Discovery of the
Inverdale gene (FecX). Proc NZ Soc Anim Prod 55:289-293.
De Gortari MJ, Freking BA, Cuthbertson RP, Kappes SM, Keele JW, Stone
RT, Leymaster KA, Dodds KG, Crawford AM, Beattie CW. 1998. A
second generation map of the sheep genome. Mamm Genome 9:204209.
De Gortari MJ, Freking BA, Kappes SM, Leymaster KA, Crawford AM,
Stone RT, Beattie CW. 1997. Extensive genomic conservation of cattle
microsatellite heterozygosity in sheep. Anim Genet 28:274-290.
Diez Tascon C, Bayon Y, Arranz JJ, San Primitivo F. 1996. Investigation
on QTLs affecting milk production in sheep using microsatellite markers. Proc 25th Int Conf Anim Genet, Tours, France, p 189.
Dolling CHS. 1997. Standardized genetic nomenclature for sheep. In:
Piper L, Ruvinsky A, editors. The Genetics of Sheep. New York: CAB
International, p 593-601.
Forbes SH, Hogg JT, Buchanan FC, Crawford AM, Allendorf FW. 1995.
Microsatellite evolution in congeneric mammals: Domestic and bighorn sheep. Mol Biol Evol 12:1106-1113.
Francis SM, Bickerstaffe R, Clarke JN, O'Connell D, Hurford AP. 1994.
Effect of selection for glucose tolerance in sheep on carcass fat and
plasma glucose, urea and insulin. J Agric Sci Cam 123:279-286.
Franklin, IR. 1997. Systematics and phylogeny of the sheep. In: Piper L,
Ruvinsky A, editors. The Genetics of Sheep. New York: CAB International, p 1-12.
Galloway SM. Hanrahan V, Dodds KG, Potts MD, Crawford AM, Hill DF.
1996. A linkage map of the ovine X chromosome. Genome Res 6:667677.
Galloway SM, Hanrahan V, Potts MD, Hill DF. 1995. Genetic markers in
Inverdale (FecX) sheep. Proc NZ Soc Anim Prod 55:307-309.
Glazko VIL, Owen JB, Ap Dewi I, Axford REF. 1997. An association of
haemoglobin protein (HBB) with ovulation rate in Cambridge sheep.
Anim Sci 64:279-282.
Gootwine E, Ofir R. 1996. Polymorphism at the growth hormone locus and
milk production in Awassi dairy sheep: Proc 25th Int Conf Anim Genet,
Tours, France, p 189.
Gulland FM, Albon SD, Pemberton JM, Moorcroft PR, Clutton-Brock TH.
1993. Parasite associated polymorphism in a cyclic ungulate population. Proc R Soc Lond B Biol Sci 254:7-13.
Harris A. 1997. Towards an ovine model for cystic fibrosis. Hum Mol
Genet 6:2191-2193.
Imam-Ghali M, Saidi-Mehtar N, Guerin G. 1991. Sheep gene mapping:
Additional DNA markers included (CASB, CASK, LALBA, IGF-1 and
AMH). Anim Genet 22:165-172.
Jolly RD, Martinus RD, Palmer DN. 1992. Sheep and other animals with
ceroid lipofuscinosis: Their relevance to Batten disease. Am J Med
Genet 42:605-614.
Jopson NB, McEwan JC, Young MJ, Stuart SK, Veenvliet BA, Littlejohn
RP, Suttie JM. 1998. Body composition and growth hormone profiles in
first-cross progeny of genetically lean and fat sheep. Proc 6th World
Congress Genet Applied Livestock Prod, Armidale, Australia 24:157160.
Lauvergne JJ, Dolling CHS, Renieri C. 1996. Mendelian Inheritance in
Sheep 1996 (MIS 96). COGOVICA/COGNOSAG, Clamart, France:
University of Camerino, Italy, p 1-214.
Lord EA, Lumsden JM, Dodds KG, Henry HM, Crawford AM, Ansari HA,
Pearce PD, Maher DW, Stone RT, Kappes SM, Beattie CW, Montgomery GW. 1996. The linkage map of sheep chromosome 6 compared
with the orthologous regions in other species. Mamm Genome 7:373376.
Volume 39, Numbers 2 and 3
1998
Lyapunova EA, Bunch TD, Vorontsov NN, Hoffman RS. 1997. Chromosomal complement and taxonomical position of Severtsov wild sheep
(Ovis ammon severtzovi). Zool Zhurnal 76:1083-1093.
Maijala K. 1997. Genetic aspects of domestication, common breeds and
their origin. In: Piper L, Ruvinsky A, editors. The Genetics of Sheep.
New York: CAB International, p 13-49.
Mann SM, Burkin DJ, Grin DK, Ferguson-Smith MA. 1997. A fast, novel
approach for DNA fibre-fluorescence in situ hybridization. Chromosome Res 5:145-147.
Montgomery GW, Crawford AM. 1997 The sheep linkage map. In: Piper
L, Ruvinsky A, editors. The Genetics of Sheep. New York: CAB
International, p 297-351.
Montgomery GW, Galloway SM, Penty JM, Hill DF. 1994. Gene mapping
and reproduction in sheep. Mol Biol (Life Sci Adv) 13:291-302.
Montgomery GW, Henry HM, Dodds KG, Beattie AE, Wuliji T, Crawford
AM. 1996. Mapping of the Horns (Ho) locus in sheep: A further locus
controlling horn development in domestic animals. J Hered 87:358363.
Montgomery GW, Kinghorn BP. 1997. Recent developments in gene mapping and progress towards marker-assisted selection in sheep. Aust J
Agric Res 48:729-741.
Morris CA. 1998. Responses to selection for disease resistance in sheep and
cattle in New Zealand and Australia. Proc 6th World Cong Genet Appl
Livestock Prod, Armidale, Australia 27:295-302.
Morris CA, McEwan JC, Fennessy PF, Bain WE, Greer GJ, Hickey SM.
1997. Selection for high and low backfat depth in Coopworth sheep:
Juvenile traits. Anim Sci 65:93-103.
Morris CA, Towers NR, Wheeler M, Amyes NC. 1995a. A note on the
genetics of resistance or susceptibility to ryegrass staggers in sheep. NZ
J Agric Res 38:367-371.
Morris CA, Towers NR, Wheeler M, Wesselink C. 1995b. Selection for or
against facial eczema susceptibility in Romney sheep, as monitored by
serum concentrations of a liver enzyme. NZ J Agric Res 38:211-129.
Nicholas FW. 1997. Genetics of morphological traits and inherited disorders. In: Piper L, Ruvinsky A, editors. The Genetics of Sheep. New
York: CAB International, p 87-132.
Nicoll GB, Burkin HR, Broad TE, Jopson NB, Greer GJ, Bain WE, Wright
CS, Dodds KG, Fennessy PF McEwan JC. 1998. Genetic linkage of
microsatellite markers to the Carwell locus for rib-eye muscling in sheep.
Proc 6th World Cong Genet Appl Livestock Prod, Armidale, Australia
26:529-532.
Nicoll GB, McEwan JC, Dodds KG, Jopson NB. 1997. Genetic improvement in the Landcorp Lamb Supreme terminal sire flocks. Proc Assoc
Advmt Anim Breed Genet 12:68-71.
Parsons YM, Cooper DW, Piper LR. 1994. Evidence for linkage between
high-glycine-tyrosine keratin gene loci and wool fibre diameter in a
Merino half-sib family. Anim Genet 25:105-108.
Parsons YM, Fleet MR, Cooper DW. 1997. Investigation of the gene responsible for the recessive pigmentation in Australian Merino sheep.
Proc Assoc Advmt Anim Breed Genet 12:447-451.
Pearce PD, Ansari HA, Maher DW, Malcolm AA, Stewart-Scott IA, Broad
TE. 1994. New Robertsonian translocation chromosomes in domestic
sheep (Ovis aries). Cytogenet Cell Genet 67:137-140.
Piper L, Ruvinsky A. 1997. The Genetics of Sheep. New York: CAB
International.
Ponzoni RW. 1997. Genetic resources and conservation. In: Piper L,
Ruvinsky A, editors. The Genetics of Sheep. New York: CAB International, p 437-469.
Popescu CP (Coordinator), Long S, Riggs P, Womack J, Schmutz S, Fries
R, Gallagher DS. 1996. Standardization of the cattle karyotype nomenclature: Report of the committee for the standardization of the cattle
karyotype. Cytogenet Cell Genet 74:259-261.
Powell BC. Rogers GE. 1994. Differentiation in hard keratin tissues, hair
and related structures. In. Leigh I, Watt F, Lane EB, editors. Keratinocyte Handbook. Cambridge: Cambridge University Press, p 401436.
Raadsma HW, Attard GA, Nicholas FW, Egerton JR 1996. Disease resistance in Merino sheep: Genetic heterogeneity in response to vaccination
169
with Dichelobacter nodosus and clostridial antigens. J Anim Breed
Genet 113:181-199.
Robinson N, Ward W, Matthews M. 1995. Allelic variation linked to FGF1
is associated with reduced wool fibre diameter and greasy fleece weight
in sheep. Proc 6th Australas Gene Map Workshop NZ Genet Soc,
Dunedin, New Zealand (Abstract 12).
Rogers GR, Hickford JGH, Bickerstaff R. 1994. A potential QTL for wool
strength located on sheep chromosome 11. Proc 5th World Cong Genet
Appl Livestock Prod, Guelph, Ontario, Canada, p 291 -294.
Tate ML, Goosen GJ, Patene H, Pearse AJ, McEwan KM, Fennessy PF.
1997a. Genetic analysis of Pere-David x red deer interspecies hybrids.
JHered 88:361-365.
Tate ML, Mathias KM, McEwan KM, Anderson RN. 1997b. Translation of
information between human and livestock gene maps using a deer
interspecies hybrid mapping panel. Proc NZ Soc Anim Prod 57:301-302.
170
Tebbutt SJ, Harris A, Hill DF. 1996. An ovine CFTR variant as a putative
cystic fibrosis causing mutation. J Med Genet 33:623-624.
Vaiman D, Schibler L, Burgeois F, Oustry A, Amigues Y, Cribiu EP. 1996.
A genetic map of the male goat genome. Genetics 144:279-305.
Ward W, Robinson N, Matthews M. 1995. Total genome screen of a wool
trait flock using random microsatellite markers. Proc 6th Australas
Gene Map Workshop NZ Genet Soc, Dunedin, New Zealand (Abstract
84).
White JA, McAlpine PJ, Antonarakis S, Cann H, Eppig JT, Frazer K, Frezal
J, Lancet D, Nahmias J, pearson P, Peters J, Scott A, Scott H, Spurr N,
Talbot Jr C, Povey S. 1997. Guidelines for human gene nomenclature
(1997). Genomics 45:468-471.
Wuliji T, Montgomery GW, Dodds KG, Andrews RN, Beattie AE, Turner
PR, Rogers J. 1995. Establishing a flock for gene mapping in wool
traits. Proc NZ Soc Anim Prod 55:285-288.
ILAR Journal