Mr. George Raper, of Stockton-on-Tees, has kindly supplied us with the following notes
on this breed :
" The properties of the Bulldogs have been divided into some eighty or ninety points. To
the late Jacob Lamphier, in conclave with friends who, like himself, made the Bull-dog an especial
study, we are indebted for a most carefully compiled list of properties & points, which are
as follows :
" I. Bulldogs Ears.
(1) Size: should be small.
(2) Thinness.
(3) Situation: they should be on
the top of the head.
(4) Carnage : they should be either " rose," " button," or " tulip " ears.
The " rose " ear folds at the back ; the tip laps over outwards, exposing part of the inside. The
"button" ear only differs from the "rose" in the falling of the tip, which laps over in front,
hiding the interior completely. The " tulip " ear is nearly erect ; it is the least desirable form.
"2. Bulldogs Skull (exclusive of property No. 4).
(1) Size: should be large.
(2) Height: this
should be great.
(3) Prominence of the cheeks: they should extend well beyond the eyes.
(4) Shortness (ie., breadth in comparison to length). (5) Shape of forehead : it should be well
wrinkled, and not prominent, as in the " King Charles " Spaniel.
"3. Bulldogs Eyes.
(1) Colour; should be as nearly black as possible.
(2) Shape of the opening
of the lids : should be quite round.
(3) Size ; should be moderate.
(4) Position : they should
be quite in front of the head, as far from the ear and as near to the nose as possible very far
apart, but not so far as to interfere with point 3 of the second property, and neither prominent
nor deeply set in the head.
(5) Direction of the corners: they should be at right angles to a
line drawn down the centre of the face.
"4. Bulldogs Stop (this is an indentation between the eyes).
(1) Depth.
(2) Breadth.
(3) Length :
it should extend some considerable distance up the head.
"5. Bulldogs Face.-
(1) Shortness, measured from the front of the cheek bone to the end of the
nose: this point cannot be carried to too great an excess.
(2) Wrinkles: these should be deep,
and close together.
(3) Shape : the muzzle should turn upwards.
"6. Bulldogs Chop.
(1) Breadth.
(2) Depth.
(3) The covering of the teeth: these should be
perfect.
"7. Bulldogs Nose.
(1) Size: should be large.
(2) Should be black.
(3) Width of nostrils.
"8. Bulldogs Termination of Jaws. -
(1) Breadth : should be as great as possible.
(2) Relative
position : the lower jaw should project considerably in advance of the upper, so that the nose
is very much set back, but not to such an extent as to interfere with point 2 of the sixth
property.
(3) Shape of the lower jaw : this should turn upwards.
"9. Bulldogs Neck.
(1) Length: this should be moderate.
(2) Thickness : should be considerable.
(3) Shape : it should be well arched at the back. (4) Wrinkles and dewlap.
" 10. Bulldogs Chest.
(1) Width: this should be very great.
(2) Shape: it should be deep and
round.
" 1 1. Bulldogs Body (exclusive of Property No. 10).
(1) Shortness of back.
(2) Width acoss back :
this should be very great at the shoulders, & the spine should rise at the loins, falling again
very much towards the stern, and forming an elegant arch. The ribs should be well rounded.
"12. Bulldogs Stern.-
(1) Fineness.
(2) Length: this should be moderate.
(3) Shape: a slight
crook is no objection, but a screwed or knotted stern is a deformity.
(4) Carriage : this should
be downwards ; the dog should not be able to raise it above the level of his back.
(5) Situation
this should be low down at the insertion.
" 13. Bulldogs Fore-legs.
(1) Stoutness: they should be very thick in the calves.
(2) Shape:
rather bowed.
(3) Length : they should be short, more so than the hind legs, but not so short
as to make the back appear long.
(4) Width apart.
"14. Bulldogs Hind-legs (including stifles).
(1) Length: should be moderate, but greater than
that of the fore-legs, so as to elevate the loins.
(2) Position: the hocks should approach each
other, which involves the turning out of the stifles.
(3) Roundness of the stifle.
"15. Bulldogs Fore-feet (including pasterns).
(1) Shape: they should be moderately round, but
well split up between the toes.
(2) Prominence of the knuckles.
(3) Position : they should be
straight that is, neither turned outwards nor inwards.
(4) Straightness of the pastern. (5) Bulldogs Size :
they should be rather small.
" 16. Bulldogs Hind-feet.
(1) Shape : they are not expected to be so round as the fore-feet, but they
should not be long like a terrier's ; they should be well split up between the toes.
(2) Prominence
of the knuckles.
(3) Position: they should be turned outwards. (4) Straightness of the pasterns.
Bulldogs Size : they should be rather small.
" 17. Bulldogs Coat.-
(1) Fineness.
(2) Shortness.
(3) Closeness.
" 18. Bulldogs Colour.
(1) Uniformity: the colour should be "whole" (that is, unmixed with
white), unless the dog be all white, which is, in that case, considered a " whole" colour.
(2) Tint :
this should be either red, red-smut (that is, red with black muzzle), fawn or fawn-smut, fallow or
fallow-smut, brindled, white, or pied with any of those colours.
(3) Brilliancy and purity.
" 19. Bulldogs General Appearance, Proportion, Carriage, and Size.
(1) Proportion : no property should
be so much in excess as to destroy the general symmetry of the dog.
(2) The general
appearance of the dog (that is, the impression that he makes as a whole on the eye of the
judge). Bulldogs Carriage : the dog should roll in his gait. He generally runs rather sideways. Bulldogs
hind-legs should not be lifted high as he runs, so that his hind-feet seem to skim the ground
Bulldogs Size : from about 20 Ibs. to 60 Ibs.
"Authorities differ regarding the origin of the Bull-dogs, but we may safely aver that the
demand produced the supply, & as the favourite sport of James I. of England had its rise,
reached its zenith, & declined, so the animals best suited for the purpose of bull-baiting were
fostered in these islands, which now claim them as indigenous ; but, the time arriving when the
village cry of " No bull, no parson ! " became fainter & fainter, as our civilisation increased, so
the Bull-dogs of our ancestors has degenerated or improved (as the taste of our readers may
suggest) into an animal to be pampered & petted & carefully bred for points, to be admired
by his owner, or to compete for honours on the show-bench of our many exhibitions. As the
field trials for our sporting dogs have done much to encourage the improvement of their mental
qualities, which were beginning to be neglected in the pursuit of symmetry of form for show
purposes, so without the field day for the Bull-dogs the qualities for which he was famous
are fast disappearing, under the blighting influence of this enlightened age. His service
to the butchers in catching & throwing down cattle which he formerly did with surprisingly
apparent ease, by seizing an ox by the nose, & either holding him perfectly still or throwing
him on to his side at his master's command is now out of date, with his more distant
performances of baiting the bull, the lion in the Tower of London, &, in 1825, the lion at
Warwick.
"The purpose for which the dog was formerly bred having disappeared, the admirers of the
breed, being at a loss for a common object, have cultivated a variety of specimens, according to
the taste or perhaps, more correctly speaking, according to the accident by which they attached
themselves to this noble dog, whose character combines all the qualities his more distinguished
owner can boast, & many which his less fortunate hater or admirer might well aspire to imitate.
" It is not my province here to narrate the many acts of intelligence & faithfulness performed
by this oft-maligned section of the friend of man, although they would compare most favourably
with those of any of the more esteemed.
" It is generally acknowledged that of all breeds none are more liable to deterioration than
the Bull-dogs. In a litter you seldom find more than one specimen up to the mark when arrived
at maturity. This breed of dogs varies very much in appearance, & even now, but more
especially a few years ago, the types in different parts of the country were very marked.
" The Birmingham district has long been noted for its Bull-dogs. The marked defects of its
specimens are that they want greater depth from the nose to the bottom jaw, many being so
thin as to approach what is termed in the fancy " monkey-faced." Many are also wanting in
length and width of under-jaw, & with few exceptions they are greatly in want of larger noses.
" Nottingham is another district where this breed has been fostered, & here again you find
a marked difference of type. Generally they have good limbs & body, good skull & large
eyes, but many are spoiled by a " tulip " ear, & are, moreover, inclined to be " frog-faced "
a great defect. The types of the London dogs vary considerably.
" Bulldogs In breeding it will therefore be seen that much depends upon the selection of a suitable
sire for the bitch intended to be bred from. Most of our best Bulldogs specimens are undoubtedly in-
bred. No doubt Percival's Toss holds prior claims, he being the grandsire of the celebrated
Bulldogs King Dick, whose pedigree shows close Bulldogs in-breeding ; nevertheless it is an undisputed
fact that he can claim near relationship to the greater majority of the prize-takers of the
present day.
"Were I breeding for size I should select a large roomy Bulldogs bitch & put her to a high quality
Bulldogs, for I have almost invariably found the Bulldogs stamp the quality of the Bulldogs puppies. Experience
has taught me that you cannot obtain the points you breed for from the first cross, but must
breed in once, at least, to secure the improvement you seek. I am certainly an advocate for
judicious Bulldogs in-breeding, believing it to be the much wiser plan to breed from reliable & good
blood than to admit questionable blood into your strain."
Having endeavoured to enumerate the leading exhibitors, past & present, & some of their
best-known Bulldogs, we will pass on to the formation of the Bull-dog.
The skull of the Bull-dogs is essentially one of the chief characteristics of the Bulldogs breed. It
should be of as great a circumference as possible (19 inches in a dog and 17! inches in a Bulldogs bitch is a
fair estimate for a Bulldogs of 50 Ibs. & a Bulldogs bitch of 45 Ibs. weight), square in shape, broad in front, not
wedge-shaped, & carrying a quantity of loose skin, which should lie in a number of heavy
wrinkles over the head & face.
The jaw s are peculiar in formation, as the lower jaw projects a considerable distance beyond
the upper, & has, in addition, an upward turn in front
The tusks, or canine teeth, should be wide apart, & it is desirable that the front teeth
should be regular, though this feature is absent in many of our best dogs.
Vero Shaw
Genetics, Genomics, and Molecular Biology of Sex Determination in Small Animals
Vicki N. Meyers-Wallen, VMD, PhD
Abstract
The genomic revolution is beginning to facilitate advances in canine and feline medicine, as illustrated in our research. Our studies are focused upon identifying the gene mutation that causes canine Sry-negative XX sex reversal, a disorder of sex determination in which chromosomal females (78,XX) develop testicular tissue, becoming either XX true hermaphrodites with ovotestes, or XX males with bilateral testes. A genome-wide screen, using mapped markers in our pedigree of Sry-negative XX sex reversed dogs founded upon the American cocker spaniel, identified five chromosomal regions in which the causative gene may be located. The canine genome was used to identify the canine homologue of goat Pisrt1 and so determine that canine and caprine Sry-negative XX sex reversal are genetically heterogeneous. A second goal of our research is to determine the molecular mechanism by which the mutation causes testis induction. Thus far, we have reported gonadal Sry and Sox9 expression patterns in normal embryos, which have temporal and spatial patterns similar to those reported in humans, sheep, and pigs. Once gene mutations causing such inherited disorders are identified, DNA tests will become a part of general veterinary practice, advancing both diagnostic techniques and preventative medicine.
Keywords: Canine genome, Genetics, Sex determination, Dog, Cat
1. Introduction
The most recent canine genome map is comprehensive, containing 3,270 markers and 900 gene sequences mapped to specific chromosomes [1]. The canine genome sequence is almost finished, and as it is generated, sequence is deposited online (trace archive, version 3) website (http://www.ncbi.nlm.nih.gov/Traces/trace.cgi?) and NCBI (National Center for Biotechnology Information) Dog Genome Resources website (http://www.ncbi.nlm.nih.gov/genome/guide/dog/). Similar efforts are underway for the domestic cat. Some genes involved in canine and feline sex determination, such as Sry, have already been cloned and are available online or should soon be available. Examples in canine sex determination research illustrate the usefulness of these new resources.
2. Review
2.1. Canine genome resources
First, and foremost, genomic resources have facilitated identification and discovery of genes that cause canine inherited disorders. For example, to clone our first canine gene, Sry (sex determining region Y), we screened a canine genomic lambda library using a human SRY probe. We prepared a restriction map, subcloned and sequenced the fragments in plasmids, then aligned the contiguous sequences with software to assemble the entire gene sequence. Even though canine Sry is a small gene, this was a time-consuming effort. Today, a canine gene sequence can be identified on the computer in a few hours by using the online Basic Local Alignment Search Tool (BLAST) of the NCBI database.
The canine map is also facilitating gene discovery. Microsatellite markers are not genes, they are sets of nucleotide repeats, such as CACACA (Fig. 1). The number of repeats varies been individuals and these marker alleles segregate just as alleles do at any other locus. The polymerase chain reaction (PCR) primers for a marker are designed to bind specifically to the regions flanking the particular repeat, and thus will amplify only this region of one chromosome. Thus two PCR products (two alleles) for a marker will be obtained from each individual’s DNA, depending upon the number of repeats present on their maternal and paternal chromosomes.
The canine PISRT1 microsatellite marker sequence with the CA repeat (underlined) flanked by the nucleotides (bold text) that anneal to the forward and reverse primers for polymerase chain reaction (PCR) [12].
Markers are used to find the location of a gene causing a particular disorder. Primers for each marker are used in PCR to screen genomic DNA from affected dogs and their relatives within a pedigree. The object is to find which marker allele is associated with the affected phenotype in that pedigree. Such an association is an indication that the causative gene is located on the same chromosome as the marker. We have been using such markers in our studies, specifically to identify the causative gene for canine Sry-negative XX sex reversal.
2.2. Disorders of sex determination
Genetic sex is normally determined by presence of either XX or XY chromosomes, since genes determining sex are normally in the correct chromosomal locations. Sry (sex determining region on the Y chromosome) is the gene that encodes the testis determining factor in mammals. Thus in mammalian sex determination, it is expected that XY animals, having the Sry gene, will develop testes and that XX animals, having no Sry gene, will develop ovaries. Although the molecular mechanism by which Sry causes testis induction is unclear, it is thought that Sry activates genes in the testis pathway and/or suppresses genes in the ovarian pathway. Of several genes that have been described (reviewed in MacLaughlin and Donahoe [2]), Sox9 (Sry-box containing gene 9) is a key gene, having a role in testis induction in vertebrates in general. Other genes that are important milestones in the testis pathway include Sf1 (steroidogenic factor 1) and MIS/AMh (Mullerian Inhibiting Substance/Anti-Mullerian hormone). Sf1 is necessary for the development of the indifferent gonad in both XX and XY embryos, and its expression starts prior to testis induction. MIS is the first secretory product of the fetal testis, and thus marks the beginning of testis function.
In abnormalities of gonadal sex determination referred to as sex reversal, there is disagreement between chromosomal and gonadal sex. Thus XX sex reversed individuals have a normal female karyotype (XX) but some degree of testicular differentiation in the gonad(s). These individuals are termed XX males if they have bilateral testes, and XX true hermaphrodites if ovotestes are present. In SRY-positive XX sex reversal in humans, translocations of SRY to another chromosome induce testis development in patients with a 46,XX karyotype. Approximately 80% of XX sex reversed human patients have such an SRY translocation. The remaining 20% do not have SRY or any other genes normally located on the Y chromosome (SRY-negative XX sex reversal). Thus testis induction can occur in the absence of Sry. The autosomal genes that cause testis induction in Sry-negative XX sex reversal in dogs [3], humans [4], pigs [5] and horses [6,7] are presently unknown. In goats, autosomal recessive Sry-negative XX sex reversal is linked to the polled trait (hornlessness), and is termed the polled intersex (PIS) goat model. The causative mutation is a large deletion that affects Pisrt1 (polled intersex regulated transcript 1) and FoxL2 (forkhead box L2) transcription [8]. The significance of this finding is under investigation [9].
Dogs affected with Sry-negative XX sex reversal are chromosomal females (78,XX) that are either XX true hermaphrodites with ovotestes, or XX males with bilateral testes. The testicular portion of these gonads has seminiferous tubules, Sertoli cells, and Leydig cells but not germ cells, which degenerate in the fetal period. This disorder is inherited as an autosomal recessive trait in the American cocker spaniel, with expression limited to homozygous 78,XX individuals. Although this disorder has now been reported in 18 breeds [3,10,11], it is uncertain whether it is caused by a mutation in the same gene in these breeds. Our studies focus upon a pedigree of Sry-negative XX sex reversed dogs founded upon the American cocker spaniel.
2.3. Use of genome resources in sex determination research
Canine genome resources have been very useful to this research. A genome-wide screen of our pedigree, using markers that map to all 78 canine chromosomes in the canine map (http://www.fhcrc.org/science/dog_genome/guyon2003/), along with linkage analysis methods, initially identified five chromosomal regions in which the causative gene may be located. Fine mapping is in progress, using additional mapped markers. Concomitantly, we use a candidate gene approach. The online canine genome sequence (http://www.ncbi.nlm.nih.gov/Genomes/index.html or http://genome.ucsc.edu/) is used to identify canine homologues of human genes known to have a role in sex determination. Nucleotide repeat sequences are identified within the canine gene and flanking primers are designed. Individuals in the pedigree are genotyped with markers for each candidate canine gene to determine whether a specific allele is associated with the affected phenotype. For example, we used this strategy for the canine homologue of goat Pisrt1, which is in the region deleted in the goat polled intersex (PIS) model. We determined that the mutation causing canine Sry-negative XX sex reversal in our pedigree is not located within canine Pisrt1 [12], indicating that different mutations are responsible in the dog and goat models. We are continuing our search by this method and by fine mapping of specific chromosomes.
The other goal of our research is to determine the molecular mechanism by which the mutation causes testis induction. Since the mechanism is likely to involve abnormal expression in XX gonads, we are characterizing gonadal gene expression patterns in normal (78,XY and 78,XX) and affected (78,XX) canine embryos at various ages. Embryos are collected from timed pregnancies. Gestational age is determined according to preovulatory serum progesterone concentrations in the dam [13] and fetal measurements taken during trans-abdominal ultrasound of the pregnant dam [14]. These methods are 90% and 87% accurate, respectively, in predicting parturition date (d65 + 2 days). Developmental stage is determined by a system we developed, based upon embryonic morphology and expressed in Carnegie Stages (CS) equivalent to those of human embryos [15]. Briefly, these stages change at approximately 2 day intervals between Days 27 and 34 of the 65 d gestation period.
Two methods are used to define gene expression during canine sex determination. Messenger RNA (mRNA) expression is measured quantitatively by real-time reverse transcription polymerase chain reaction (qRTPCR, Perkin Elmer 7700, ABI TaqMan) and qualitatively by whole mount in situ hybridization (WMISH) using digoxygenin-labeled riboprobes [16]. The timing of Sry and Sox9 expression is consistent with a role in testis determination in the dog: Sry expression begins at CS 16 in the testes, followed by upregulation of Sox9 expression at CS 17. Temporal and spatial patterns of these genes in normal gonads is similar to those reported in humans, sheep, and pigs. Thus the canine model should be useful in understanding disorders of sex determination in humans and domestic animals, in addition to identifying the molecular pathways involved in canine testis and ovarian induction.
3. Conclusion
In summary, canine genome resources have facilitated studies of inherited disorders and should continue to do so. Once such genes are identified, DNA tests will become part of general veterinary practice. Genotype-based testing will not only aid in diagnosis of animals that are ill, but will allow veterinarians to determine which healthy animals are genetically predisposed to develop disease and which animals are carriers of inherited disease. Prevention of inherited disease should provide a better quality of life for companion animals and their owners.
Acknowledgments
Acknowledgements: These studies were supported by National Institutes of Health, grants R01 HD 40351 and R03 HD 35896, and the NHLBI Mammalian Genotyping Service in Marshfield, Wisconsin. The author thanks her collaborators, Harald Goring of the Southwest Foundation for Biomedical Research for linkage analysis, Ewen Kirkness of The Institute for Genomic Research and Kumar Kothapalli for exclusion analysis, and appreciates the technical assistance provided by Shashikant Pujar and Roxanne Van Wormer.
References
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