Genetic Regulation of Dog Body Structure Total Size: Unlike most mammalian species, dogs show extreme diversity in body size. Sutter (2007) found that a single allele of the gene encoding insulin-like growth factor 1 (IGF-1) is shared by all small dog breeds but is nearly absent from large dog breeds. Blood concentrations of IGF1 protein also correlate with body size in toy, miniature, and standard poodles. Three different loci regulate IGF-1 activity. CFA15 contains the IGF1 gene that governs miniature size. This autosomal recessive allele is found in 9 small breeds and almost absent from 30 large breeds. The autosomal recessive allele at CFA 15 contains a single 1bp SNP in Exon 3 of IGF-1. CFA3 has an IGF1-Receptor autosomal recessive allele that is responsible for small size in dachshunds and Brittany spaniels. CFA10 contains a gene called HMGA2 that has been associated with small size. Dogs exhibit the widest range in size of any animal species. This Irish wolfhound (left) and Chihuahua mix (right) show this extreme range in size. Putting aside anatomic challenges, the two breeds can (in theory) reproduce successfully. However birth of the offspring would likely be fatal to either the mother or pups. The wolfhound would be predicted to have significantly higher circulating levels of IGF-1 than the Chihuahua mix.
These breeds have been genotyped and shown to be homozygous for at least one of the IGF-1 haplotypes linked to small size. Affenpinscher Airedale Am. Eskimo dog American Staffordshire American water spaniel Australian cattle dog Australian Basenji Basset griffon vendeen petit Beagle Bedlington Bichon frise Border Boston Brittany Brussels Griffon Bull Bulldog Cairn Cavalier King Charles spaniel Cesky Chihuahua Chinese crested Clumber spaniel Cocker spaniel Dachshund Dandie Dinmont English spring spaniel Fox Fox (toy) French bulldog Glen of Imaal Havanese Irish Italian greyhound Jack Russell Japanese chin Lakeland Lhasa apso Maltese Manchester (toy) Miniature pinscher Norfolk Norwich Nova Scotia duck tolling retriever Papillon Pekingese Pomeranian Poodle (miniature) Poodle (toy) Pug Schipperke Schnauzer (miniature) Scottish Sealyham Shetland sheepdog Shiba inu Shih tzu Silky Tibetan spaniel Tibetan Welsh corgi Welsh springer spaniel Welsh West highland white Whippet Yorkshire Surprisingly, rottweilers carry the IGF-1 allele for small size too. Their compensatory mechanism is not yet known.
These breeds LACK the main G to A SNP linked with small size. Akita Bernese mountain dog Bullmastiff Great Dane Great Pyrenees Irish wolfhound Mastiff Saint Bernard Schnauzer (giant) Leg Length: Shortened legs relative to body size are a result of chondrodysplasia. An autosomal dominant allele, it is the result of an FGF4 retrogene located on CFA 18. It causes a characteristic short-limb phenotype. These breeds have short limbs due to this allele. They are fixed alleles in the breeds, so all F1 generation crosses will have chondrodysplasia. Basset hound Basset Petit Griffon Vendeen Cairn Corgi Dandie Dinmont Daschshunds Glen of Imaal Pekingese Scottish Shih tzu Skye Swedish valhund West highland At least 3 breeds are homozygous for the allele, but because they are small overall, their legs do not look abnormally short. However, they do carry the allele and F1 puppies from mating with larger dogs will show the dysplastic legs. The breeds are: Japanese chin Chihuahua Yorkshire Two small breeds that do NOT carry the FGF4 dysplastic allele are: Pug Cocker spaniel
Large breeds (Labrador retriever, German shepherd) are not carriers. More advanced students may like to learn how the defect arose. The FGF4 gene was inserted by retrotransposition of the processed mrna. Normally, these areas tend to mutate to inactivity. However, domestication allows buildup of mildly deleterious mutations, particularly after selection. This is an example of gene duplication as a cause for morphological diversification. For more information, they should read Parker (2009). A basset hound. Note that its legs are much shorter than the overall length of its body. This is allele in the FGF4 locus is similar to that causing a type of human dwarfism. Skull Shape: This phenotype is best reserved for an advanced class problem. Brachycephaly (block-shaped skulls like those in bulldogs and boxers) have been tentatively linked to a 296kb QTL in CFA 1. This region includes the coding region for Thrombospondin-2 (TSP-2). However, no alternative allele has been identified, which suggests that some regulatory protein acting on TSP-2 is the actual source for the brachycephalic phenotype. It is also important to point out that brachycephaly occurs in several distantly related dog clades, suggesting that the responsible allele has arisen more than one time. Brachycephalic skull shape is inherited as either autosomal dominant or codominant, but also interacts with other genes. This trait is best used as an example of gene interactions.
This English bulldog has the classical smashed nose of a brachycephalic skull. Its snout is extremely short, such that the nose protrudes directly from between its eyes. Many brachycephalic breeds have partly obstructed nasal passages, so they pant and drool excessively. Lacking proper cooling, brachycephalic dogs overheat extremely quickly. Other loci that affect the skeleton: SOX9: Skeletal morphology of greyhounds and britttany spaniels. ZHFX3: A transcription factor affecting cranial morphology of greyhounds. LRIG3: Elongated body axis of greyhounds. SEMA3D: Morphology of dachshunds. Coat Structure Three interacting genes are largely responsible for the length and texture of a dog s coat: FGF-5 (L locus), R-spondin 2 (W locus), and keratin-71 (R locus). Together the R, W, and L loci produce seven different phenotypes: Short plain hair (e.g. Basset Hound) Short wiry hair (e.g. Australian Terrier) Curly-wiry hair (e.g. Airedale Terrier) Long hair (e.g. Golden Retriever) Long with furnishings (e.g. Bearded Collie) Long and curly (e.g. Irish Water Spaniel) Long and curly with furnishings (e.g. Bichon Frisé) (Reprinted from (Cadieu, 2009)).
Coat Length (L): Coat length is controlled by the FGF5 locus on CFA 32. A short, smooth coat phenotype is wild type. A single nucleotide conversion from G to T converts Cys-95 to Phe in Exon 1. The T allele is autosomal recessive. Short-haired dogs have the GG (ancestral) or GT (hybrid) genotype. Long haired coats are the result of a TT genotype. For basic problems, the T allele can be treated as a simple autosomal recessive. However, for 30% of breeds, GT genotype produces medium length hair, suggesting T may be partly penetrant. This would make an appropriate problem for more advanced students or for later in the semester. Some sources use the nucleotide sequences (GG, GT, TT) to indicate the genotype of dogs. Others use L and l, for the dominant and recessive alleles respectively. A mix of German shepherd with an unknown spitz-type breed. It has much longer hair (look at the length around the shoulders, neck, face, and flanks) compared to a bulldog, black Labrador, or greyhound, so is TT (recessive, or l/l) genotype. It also is an example of the black face mask produced by the E M allele. Coat Curliness (R): Curly coat hair results from an autosomal recessive mutation. It is caused by a single-nucleotide polymorphism in KRT71, the gene coding for keratin 71, on CFA 27. It causes a C to T change in Exon 2 from Arg-151 to Trp. Again, some sources use the nucleotide sequences, others use R and r for the two alleles.
Bichon breeds occur in both curly-haired and straight-haired forms. Left: a straight-haired Bichon breed, the Havanese. This dog likely is homozygous for the wild type allele (C/C [or, R/R]), because they are true-breeding. However, the straight to slightly wavy coat can also occur in heterozygous (C/T) dogs. Right: a curly-haired Bichon Frise. This dog will be homozygous recessive (T/T [or, r/r] genotype) Furnishings and Wiry Coat (W): The presence or absence of a wiry coat and long facial hair such as moustaches or eyebrows ( furnishings ) is controlled by an autosomal dominant allele of RSPO2, the R-spondin 2 protein, on CFA 12. A 167kb insert in the 3 UTR causes ~3-fold greater gene expression than in wild type. The dominant is indicated by W, recessive by w. Hairlessness: Mexican hairless, Peruvian hairless and Chinese crested dog breeds all share the same mutation. This allele is inherited as an autosomal semi-dominant. Heterozygotes are hairless, and dogs homozygous for the mutation die during embryogenesis. The allele is a 7bp duplication in Exon 1 of the FOXI3 gene on CFA 17. The exact function of FOXI3 gene is unknown, but other genes in the FOX family control embryonic development in mammals. The equivalent gene in mice regulates developing teeth and fur cells. Dog hairlessness is a recent mutation that arose about 4,000 years ago in Mexican hairless dogs and passed recently via inter-breeding into the other two dog breeds.
A miniature schnauzer with the classic furnishings of bushy eyebrows and a long mustache. This dog has not been trimmed recently, so we can see the characteristic long wiry hair of the breed. Although a single copy of the allele (W/-) is enough to produce the phenotype, schnauzers are true-breeding, indicating that the allele is fixed as (W/W). The Mexican hairless dog (a heterozygote), and a short-haired sibling of the breed (homozygous recessive). Xoloitzcuintlis (Xolos for short) have been present in Mexico for 3000 years, but were not established as a stable breed until the 1950s. Their history and preservation was described by breed historian Norman Pelham Wright in The Enigma of the Xoloitzcuintli. It is an excellent historical example of how local founder mutations lead to defined breeds.