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WHITE SPOTTING
Monday, 21 April 2008 14:36
Differences among dog breeds have intrigued geneticists for nearly a century. In the last few years molecular tools have become available to understand what makes a Poodle different from a Beagle. Using these new tools, two mendelian traits, white spotting (sw), inherited in a semi-dominant manner in boxers, bull terriers and several other breeds, and ridging, a characteristic dorsal band of abnormally oriented hair follicles from which the Rhodesian ridgeback takes its name have recently been unravelled by Kerstin Lindblad-Toh, Leif Andersson and their colleagues.
White spotting
They studied the absence of skin and coat pigmentation in white boxers, a semi-dominantly inherited trait in which heterozygous dogs appear part solid, part white (termed ‘flash’). White boxers suffer increased rates of deafness, reminiscent of human auditory-pigmentary disorders (Waardenburg and Tietz syndromes). By genotyping 10 white and 9 solid boxers, the mutation was mapped to a region of less than 1 Mb containing only one gene: microphthalmia-associated transcription factor. This Mitf gene is known to affect pigment-cell development in other mammals, including humans.
To map the mutation more finely, they studied a second breed, bull terriers, in which the same color trait segregates. Haplotype analysis revealed a 102-kb region with perfect genotype-phenotype correlation in both breeds. Across this region, they identified 3 polymorphisms located in or near segments of genomic sequence showing strong cross-species conservation. These 3 polymorphisms are located immediately upstream of the transcriptional start site of the melanocyte-specific (M) promoter of MITF. The M promoter of MITF is a critical regulator of melanocyte development, survival and migration. It seems likely that the mutation compromises expression of the gene and, ultimately, cell survival, specifically in melanocytes. According to this hypothesis, heterozygote animals will be spotted bull terriers and boxers carrying a white ‘flash’ because some melanocytes die late in development, whereas homozygote animals give rise to animals almost completely white because their melanocytes die early in development. Melanocytes are also required for normal function of the inner ear, which helps to explain why some white dogs are deaf.
Ridging in Rhodesian Ridgebacks
The skin from a ridged dog shows hair follicles and sebaceous glands of normal appearance but disturbed orientation. Ridgeback dogs are affected by a congenital malformation called dermoid sinus which closely resembles a neural-tube defect in humans usually termed dermal sinus. The dermoid sinus is characterized by a tubular indentation of the skin, with keratin and hair in the lumen. Dermoid sinus is closely associated with the ridge phenotype, and no ridgeless dogs with dermoid sinus have been reported.
The genetic analysis of the defect revealed a 133-kb duplication that includes genes coding for three fibroblast growth factors (FGFs), suggesting that an increased gene dosage of one or more of these paracrine signaling molecules causes the dorsal hair ridge. It is well established that tight regulation of FGF expression is crucial during embryonic development, including hair follicle morphogenesis. The mutation predisposes to dermoid sinus with low penetrance in duplication heterozygotes and with high penetrance in homozygotes.
Source: Karlsson EK, et al. Efficient mapping of mendelian traits in dogs through genome-wide association. Nature Genetics. 2007. 39 (1304-6).
DOG DNA STUDY YIELDS CLUES TO DIVERSE SIZE OF BREEDS
Wednesday, 16 April 2008 11:28
From the smallest Chihuahua to the largest Great Dane, dogs dramatically vary in size, much more than most other animals. While all dogs originated from wolves, which are of a fairly standard size and appearance, modern dog breeds display a wide diversity of traits, including size. The genetic origin of this diversity has baffled scientists, who have been trying to explain how and why size difference occurred so rapidly in dogs.
With the dog genome fully mapped scientists have discovered a genetic basis for this diversity. An international team led by researchers from the National Human Genome Research Institute (NHGRI) explored the genetic basis for size variation among dogs by comparing the DNA of various small dog breeds, including Chihuahuas, Toy Fox Terriers and Pomeranians, to an array of larger dog breeds, including Irish Wolfhounds, Saint Bernards and Great Danes. Their investigation found that variation in one gene — IGF-1, which codes for a protein hormone called insulin-like growth factor 1, is very strongly associated with small stature across all dog breeds studied.
It is now thought that a change in this gene resulted in the appearance of small dogs in the population many thousands of years ago. It is likely that people soon saw the benefits of smaller dogs, for example for protecting food stores from vermin or catching small game. This led to increasing popularity of smaller dogs as companions.
Source: Sutter NB, et al. A single IGFI allele is a major determinant of small size in dogs. Science. April 6, 2007.