Genetics and Dog Relationships

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Where did your dog come from? New tree of breeds may hold the answer

www.science.org/content/article/where-did-your-dog-come-new-tree-breeds-may-hold-answer

From the 80-kilogram Great Dane to the 1-kilogram tiny teacup poodle, there seems to be a dog for everyone. Now, the largest genetic analysis to date has figured out how those breeds came to be, which ones are really closely related, and what makes some dogs more susceptible to certain diseases.

"They show that by using genetics, you can really show what was going on as [breeders] were making these breeds," says Elinor Karlsson, a computational biologist at the University of Massachusetts Medical Center in Worcester who was not involved with the work.

After dogs were initially domesticated—likely between 15,000 and 30,000 years ago—people picked the best hunters, house guards, and herding animals to be their best friends, depending on their needs. There were dogs for war and for cuddling, for fur and meat, and for being good companions. Today dogs come in 350 or so breeds, each with specific traits and behaviors. Many arose in the past 200 years. Some studies have defined the genetics of a relatively small number of breeds, but none has been comprehensive enough to show how and when most came into existence. "The whole period in between [domestication and today] has been a black box," Karlsson says.

Elaine Ostrander and Heidi Parker, geneticists at the National Human Genome Research Institute in Bethesda, Maryland, and their colleagues spent 20 years going to dog shows, writing dog fanciers, and getting help from all corners of the world to collect DNA samples; in some cases they used already collected data. They weren't interested in determining how and when dogs were domesticated, but how all the breeds developed. Their sample now includes 1346 dogs representing 161 breeds, or not quite half of all kinds of dogs. By comparing the differences at 150,000 spots on each dog's genome, they built a family tree. "The scope of the analysis is very impressive, tour-de-force on breed evolution," says evolutionary biologist Robert Wayne of the University of California, Los Angeles, who was not involved with the work.

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Continued: ( my interest is in the dark blue ) A DNA comparison helped put 161 dog breeds into larger groups (various colors) based on their common ancestries.

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Continued:

Almost all the breeds fell into 23 larger groupings called clades, the team details today in Cell Reports. Although genetically defined, the clades also tended to bring together dogs with similar traits: Thus boxers, bulldogs, and Boston terriers—all bred for strength—fall into one clade; whereas herders like sheepdogs, corgis, and collies fall into another; and hunters like retrievers, spaniels, and setters fall into a third. The grouping of different breeds that share particular jobs suggests that ancient breeders likely bred dogs for specific purposes, choosing to care for those that were best at guarding or herding. Then, in the past 200 years, people subdivided those larger groups into breeds.

But the data also show how some breeds helped create others, as they share DNA with multiple clades. As one of the earliest small dogs, the pug, which hailed from China, was used in Europe from the 1500s onward to shrink other breeds. Thus, pug DNA is part of many other toy and small dog genomes, Parker explains.

"This is very exciting!" says Peter Savolainen, an evolutionary geneticist at the Royal Institute of Technology in Solna, Sweden, who was not involved with the work. "It shows how attractive traits from one breed [have] been bred into new breeds."

Having these clades will help veterinarians spot potential genetic problems, Parker says. For example, before vets couldn't really understand why a genetic disease called collie eye anomaly, which can distort different parts of the eye, and shows up in collies, border collies, and Australian shepherds, also occurs in Nova Scotia duck tolling retrievers. But the genetic analysis shows that this retriever has either collie or Australian shepherd ancestors that may have passed on the defective gene. "Mixing has resulted in the sharing of specific genomic regions harboring mutations which cause disease in very different breeds," Wayne says.

Wayne and Karlsson both stress that to provide more details, the researchers should work to compare whole genomes—the entire 2.5 billion bases. And as Savolainen points out, the work "is a very good first step into the origins of all dog breeds, but half of all breeds are still missing." Ostrander and Parker say they see this publication as a midpoint, not an endpoint. "We had reached a point where we could begin to do some of the things we wanted to do," Ostrander explains. "By no means are we done."

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dog - mammal - www.britannica.com/animal/dog

Dog, (Canis lupus familiaris), domestic mammal of the family Canidae (order Carnivora). It is a subspecies of the gray wolf (Canis lupus) and is related to foxes and jackals. The dog is one of the two most ubiquitous and most popular domestic animals in the world (the cat is the other). For more than 12,000 years it has lived with humans as a hunting companion, protector, object of scorn or adoration, and friend.

The dog evolved from the gray wolf into more than 400 distinct breeds. Human beings have played a major role in creating dogs that fulfill distinct societal needs. Through the most rudimentary form of genetic engineering, dogs were bred to accentuate instincts that were evident from their earliest encounters with humans. Although details about the evolution of dogs are uncertain, the first dogs were hunters with keen senses of sight and smell. Humans developed these instincts and created new breeds as need or desire arose.

Dogs are regarded differently in different parts of the world. Characteristics of loyalty, friendship, protectiveness, and affection have earned dogs an important position in Western society, and in the United States and Europe the care and feeding of dogs has become a multibillion-dollar business. Western civilization has given the relationship between human and dog great importance, but, in some of the developing nations and in many areas of Asia, dogs are not held in the same esteem. In some areas of the world, dogs are used as guards or beasts of burden or even for food, whereas in the United States and Europe dogs are protected and admired. In ancient Egypt during the days of the pharaohs, dogs were considered to be sacred.

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Origin and history of dogs - Ancestry:

Paleontologists and archaeologists have determined that about 60 million years ago a small mammal, rather like a weasel, lived in the environs of what are now parts of Asia. It is called Miacis, the genus that became the ancestor of the animals known today as canids: dogs, jackals, wolves, and foxes. Miacis did not leave direct descendants, but doglike canids evolved from it. By about 30 to 40 million years ago Miacis had evolved into the first true dog—namely, Cynodictis. This was a medium-size animal, longer than it was tall, with a long tail and a fairly brushy coat. Over the millennia Cynodictis gave rise to two branches, one in Africa and the other in Eurasia. The Eurasian branch was called Tomarctus and is the progenitor of wolves, dogs, and foxes.

Genetic evidence suggests that dogs descended directly from wolves (Canis) and that the now-extinct wolf lineages that produced dogs branched off from the line that produced modern living wolves sometime between 27,000 and 40,000 years ago. The timing and location of dog domestication is a matter of debate. There is strong genetic evidence, however, that the first domestication events occurred somewhere in northern Eurasia between 14,000 and 29,000 years ago. In this region wolves likely facilitated their own domestication by trailing nomadic people in northern Eurasia and consuming the remains of game animals that hunters left behind.

Most studies agree that domestication was not a single discrete event. It was a process that unfolded over thousands of years—likely involving dog populations that appeared in different parts of Eurasia at different times, with dogs and wild wolves continuing to interbreed with one another and with early dog populations being replaced by later ones. Some genetic studies have documented evidence of early domestication events in specific regions. One study contends that wolves were domesticated 16,300 years ago to serve as livestock in China, whereas another reports that early dogs dating from about 12,000 to 14,000 years ago came from a small strain of gray wolf that inhabited India. Genetic evidence also reveals that dogs did not accompany the first humans to the New World more than 15,000 years ago, suggesting instead that dogs came to the Americas only some 10,000 years ago. One study even suggested that some dogs have descended not from the wolf but rather from the jackal. These dogs, found in Africa, might have given rise to some of the present native African breeds.

No matter what their origins, all canids have certain common characteristics. They are mammals that bear live young. The females have mammary glands, and they suckle their offspring. The early breeds had erect ears and pointed or wedge-shaped muzzles, similar to the northern breeds common today. Most of the carnivores have similar dental structures, which is one way paleontologists have been able to identify them. They develop two sets of teeth, deciduous (“baby”) teeth and permanent teeth.

Canids walk on their toes, in contrast to an animal like the bear, which is flat-footed and walks on its heels. Dogs, like most mammals, have body hair and are homeothermic—that is to say, they have an internal thermostat that permits them to maintain their body temperature at a constant level despite the outside temperature.

Fossil remains suggest that five distinct types of dogs existed by the beginning of the Bronze Age (about 4500 BCE). They were the mastiffs, wolf-type dogs, sight hounds (such as the Saluki or greyhound), pointing dogs, and herding dogs.

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Role in human societies.

Dogs have played an important role in the history of human civilization and were among the first domesticated animals. They were important in hunter-gatherer societies as hunting allies and bodyguards against predators. When livestock were domesticated about 7,000 to 9,000 years ago, dogs served as herders and guardians of sheep, goats, and cattle. Although many still serve in these capacities, dogs are mainly used for social purposes and companionship. Today dogs are employed as guides for the blind and disabled or for police work. Dogs are even used in therapy in nursing homes and hospitals to encourage patients toward recovery. Humans have bred a wide range of different dogs adapted to serve a variety of functions. This has been enhanced by improvements in veterinary care and animal husbandry.

In ancient Egypt dogs were thought to possess godlike characteristics. They were pampered by their own servants, outfitted with jeweled collars, and fed the choicest diet. Only royalty was permitted to own purebred dogs, and upon the death of a ruler his favourite dog was often interred with him to protect him from harm in the afterlife.

Illustrations of dogs dating from the Bronze Age have been found on walls, tombs, and scrolls throughout Europe, the Middle East, and North America. Often the dogs are depicted hunting game with their human counterparts. Statues of dogs guard the entrances to burial crypts. In many cases these dogs clearly resemble modern canines. Such relics are indelible testimony to the importance that humans have given to the dog throughout the ages.

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Origin of breeds.

Once it became evident that dogs were faster and stronger and could see and hear better than humans, those specimens exhibiting these qualities were interbred to enhance such attributes. Fleet-footed sight hounds were revered by noblemen in the Middle East, while in Europe powerful dogs such as the mastiff were developed to protect home and traveler from harm.

As society changed and agriculture—in addition to hunting—became a means of sustaining life, other breeds of dogs were developed. Herding and guarding dogs were important to farmers for protecting their flocks. At the same time, small breeds became desirable as playthings and companions for noble families. The Pekingese in China and fragile breeds such as the Chihuahua were bred to be lapdogs. The terrier breeds were developed, mainly in England, to rid granaries and barns of rodents. Pointing and retrieving breeds were selected for special tasks related to aiding the hunter to find and capture game. Many breeds are extremely ancient, while others have been developed as recently as the 1800s.

Physical traits and functions - General characteristics.

Dogs come in a wide range of shapes and sizes. It is difficult to imagine that a large Great Dane and a tiny poodle are of the same species, but they are genetically identical with the same anatomic features. All dogs have 78 chromosomes, or 39 pairs of chromosomes (humans have 23 pairs), and one member of each pair comes from each parent. The normal temperature (rectal) of an adult dog is 100–102.5 °F.

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Genetics and Dog Relationships

www.americanscientist.org/article/genetics-and-the-shape-of-dogs

The "dog genome project" was launched in the early 1990s, motivated by scientists' desire to find the genes that contributed to many of the ills suffered by purebred dogs. Most dog breeds have only been in existence for a few hundred years. Many exhibit limited genetic diversity, as dog breeds are typically descended from a small number of founders, created by crossing closely related individuals. Further, breeds often experience population bottlenecks as the popularity of the breed waxes and wanes. As a result of this population structure, genetic diseases are more common in purebred dogs than in mixed-breed dogs. Scientists have been motivated to use dog populations to find genes for diseases that affect both humans and dogs, including cancer, deafness, epilepsy, diabetes, cataracts and heart disease. In doing so we can simultaneously help man and man's best friend.

The initial stages of the dog genome project involved the building of maps that allowed scientists to navigate the dog genome. Quick to follow were the production of resources that facilitated the manipulation of large pieces of dog genome DNA and a numbering of the dogs' 38 pairs of autosomes (non-sex chromosomes) as well as the X and Y chromosomes. Finally, in 2003, a partial sequence of a standard poodle was produced that spanned nearly 80 percent of the 2.8 billion base pairs that make up the dog genome. This was followed quickly by a concerted effort to fully sequence the boxer genome, producing what is today the reference sequence for the dog.

How is this information being used by geneticists today? The availability of a high-quality draft sequence of the dog genome has quite literally changed the way geneticists do their work. Previously scientists used so-called "candidate gene" approaches to try and guess which genes were responsible for a particular disease or trait of interest. By knowing something about what a gene does or what family it belongs too, we can sometimes, but not always, develop excellent hypotheses as to what happens when a specific gene goes awry. However, candidate gene approaches are often characterized by frustration and great expense. Hence, companion-animal geneticists are turning increasingly to the more sophisticated genomic approaches made possible by the success of the dog genome project.

Central to our ability to use the newly available resources is an understanding of breed structure, the strengths and limitations of the current molecular resources, and consideration of the traits which are likely to lend themselves to mapping using available resources. In this article I highlight first our current understanding of what a dog breed really is and summarize the status of the canine genome sequencing project. I review some early work made possible by this project: studies of the Portuguese water dog, which have been critical to our understanding of how to map genes controlling body shape and size, along with studies aimed at understanding the genetics of muscle mass.

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Dog Breeds - The domestic dog is believed to be the most recently evolved species from the family Canidae. Within the Canidae there are three distinct phylogenetic groups, or clades; the domestic dog shares a clade with the wolflike canids such as the gray wolf, coyote and jackals. Dogs are thought to have arisen perhaps as recently as 40,000 years ago, with initial domestication events occurring in eastern Asia. Most domestic breeds that we recognize today, however, likely are the product of human breeding over the last 200-300 years. Many of the most common modern breeds were developed in Europe in the 1800s. Some of the breeds represented in antiquity, including the greyhound and the pharaoh hound, are particularly interesting to study, as it is unclear whether dogs from these breeds are re-creations of ancient breeds or whether dogs alive today can truly trace their lineage to founders from thousands of years ago.

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Current Issue
THIS ARTICLE FROM ISSUE
SEPTEMBER-OCTOBER 2007
VOLUME 95, NUMBER 5
PAGE 406
DOI: 10.1511/2007.67.406

VIEW ISSUE
A pekingese weighs only a couple of pounds; a St. Bernard can weigh over 180. Both dogs, though vastly different in appearance, are members of the same genus and species, Canis familiaris. How dog breeds can exhibit such an enormous level of variation between breeds, and yet show strong conformity within a breed, is a question of interest to breeders and everyday dog lovers alike. In the past few years, it has also become a compelling question for mammalian geneticists.

Photograph courtesy of Tyrone Spady and the author.

The "dog genome project" was launched in the early 1990s, motivated by scientists' desire to find the genes that contributed to many of the ills suffered by purebred dogs. Most dog breeds have only been in existence for a few hundred years. Many exhibit limited genetic diversity, as dog breeds are typically descended from a small number of founders, created by crossing closely related individuals. Further, breeds often experience population bottlenecks as the popularity of the breed waxes and wanes. As a result of this population structure, genetic diseases are more common in purebred dogs than in mixed-breed dogs. Scientists have been motivated to use dog populations to find genes for diseases that affect both humans and dogs, including cancer, deafness, epilepsy, diabetes, cataracts and heart disease. In doing so we can simultaneously help man and man's best friend.

The initial stages of the dog genome project involved the building of maps that allowed scientists to navigate the dog genome. Quick to follow were the production of resources that facilitated the manipulation of large pieces of dog genome DNA and a numbering of the dogs' 38 pairs of autosomes (non-sex chromosomes) as well as the X and Y chromosomes. Finally, in 2003, a partial sequence of a standard poodle was produced that spanned nearly 80 percent of the 2.8 billion base pairs that make up the dog genome. This was followed quickly by a concerted effort to fully sequence the boxer genome, producing what is today the reference sequence for the dog.

How is this information being used by geneticists today? The availability of a high-quality draft sequence of the dog genome has quite literally changed the way geneticists do their work. Previously scientists used so-called "candidate gene" approaches to try and guess which genes were responsible for a particular disease or trait of interest. By knowing something about what a gene does or what family it belongs too, we can sometimes, but not always, develop excellent hypotheses as to what happens when a specific gene goes awry. However, candidate gene approaches are often characterized by frustration and great expense. Hence, companion-animal geneticists are turning increasingly to the more sophisticated genomic approaches made possible by the success of the dog genome project.

Central to our ability to use the newly available resources is an understanding of breed structure, the strengths and limitations of the current molecular resources, and consideration of the traits which are likely to lend themselves to mapping using available resources. In this article I highlight first our current understanding of what a dog breed really is and summarize the status of the canine genome sequencing project. I review some early work made possible by this project: studies of the Portuguese water dog, which have been critical to our understanding of how to map genes controlling body shape and size, along with studies aimed at understanding the genetics of muscle mass.

Dog Breeds
The domestic dog is believed to be the most recently evolved species from the family Canidae. Within the Canidae there are three distinct phylogenetic groups, or clades; the domestic dog shares a clade with the wolflike canids such as the gray wolf, coyote and jackals. Dogs are thought to have arisen perhaps as recently as 40,000 years ago, with initial domestication events occurring in eastern Asia. Most domestic breeds that we recognize today, however, likely are the product of human breeding over the last 200-300 years. Many of the most common modern breeds were developed in Europe in the 1800s. Some of the breeds represented in antiquity, including the greyhound and the pharaoh hound, are particularly interesting to study, as it is unclear whether dogs from these breeds are re-creations of ancient breeds or whether dogs alive today can truly trace their lineage to founders from thousands of years ago.


Adapted by Barbara Aulicino and Linda Huff from Lindblad-Toh et al. 2005.

The American Kennel Club (AKC) currently recognizes about 155 breeds of dog, but new breeds are created and given breed-recognition status frequently. What defines a dog breed? Although a dog's parentage can be recognized by its physical attributes—coat color, body shape and size, leg length and head shape, among others—the concept of a breed has been formally defined by both dog fanciers and geneticists.

Dog regulatory bodies such as the AKC define an individual's breed by its parentage. For a dog to become a registered member of a breed (say, a golden retriever), both of its parents must have been registered members of the same breed, and their parents in turn must be registered golden retrievers. As a result, dog breeds in the United States today are generally closed breeding populations with little opportunity for introduction of new alleles (variations in the genome). At a genomic level, purebred dogs are usually characterized by reduced levels of genetic heterogeneity compared to mixed-breed dogs. Breeds that derive from small numbers of founders, have experienced population bottlenecks or have experienced popular-sire effects—that is, the effect on the breed of a dog who does well in shows producing a disproportionate number of litters—display further reductions in genetic heterogeneity.

Recently, my laboratory group and others have begun to use genetic tools such as markers to define the concept of a dog breed. A genetic marker is a position in the genome where there is variability in the sequence that is inherited in a Mendelian fashion (that is, following the rules of classical genetics). Two common kinds of markers are microsatellite markers, where the variation comes from the number of times a repeat element is reiterated at a given position on a chromosome, and single-nucleotide polymorphisms (SNPs, pronounced "snips"), in which the DNA sequence varies when a single nucleotide (denoted A, C, T or G) in a sequence differs between the paired chromosomes of an individual.

These alterations are proving invaluable for understanding the role of genetic modifications both within and between breeds. Because the alleles of markers are inherited from parent to child in a Mendelian fashion, they can be used to track the inheritance of adjacent pieces of DNA through the multiple generations in a family. There are thousands of microsatellite markers and millions of SNPs distributed randomly throughout the canine genome.

In order to determine the degree to which dogs could be assigned correctly to their breed group, my lab utilized data from 96 microsatellite markers spanning all the dog's 38 autosomes in a set of 414 dogs representing 85 breeds. We found, first, that nearly all individual dogs were assigned correctly into their breed group when we used a set of statistical tools called clustering algorithms, which look for similarities in the frequency and distribution of alleles between individuals. The exceptions largely included six sets of closely related breed pairs (for example whippet-greyhound and mastiff-bullmastiff) that could only be assigned to their respective breeds when considered in isolation from other breeds.

We also showed that the genetic variation between dog breeds is much greater than the variation within breeds. Between-breed variation is estimated at 27.5 percent. By comparison, genetic variation between human populations is only 5.4 percent. Thus the concept of a dog breed is very real and can be defined not only by the dog's appearance but genetically as well.

A second part of the study used an assignment test to determine whether we could correctly identify each dog's breed by its genetic profile alone. In a blinded study, where the computer program did not know what data set came from which breed, 99 percent of dogs were correctly assigned to their breed based on their DNA profile alone.

To determine the ancestral relationship between breeds, Heidi Parker from my lab used data from the same set of dogs and sought to determine, ideally, which dog breeds were most closely related to one another. To do this we utilized a computer program called structure, which was developed by Jonathan Pritchard at the University of Chicago and his colleagues. The program identifies genetically distinct subpopulations within a group based on patterns of allele frequencies, presumably from a shared ancestral pool.

The structure analysis initially ordered the 85 breeds into four clusters, generating a new canine classification system. Cluster 1 comprised dogs of Asian and African origin—thought to be older lineages—as well as gray wolves. Cluster 2 included largely mastiff-type dogs with big, boxy heads and large, sturdy bodies. The third and fourth clusters split a group of herding dogs and sight hounds away from the general population of modern hunting dogs, the latter of which includes terriers, hounds and gun dogs. As more dog breeds have been added to the study, additional groupings have emerged.

These data are extremely useful for disease-gene mapping studies. In some cases, dogs from breeds that are members of the same cluster can be analyzed simultaneously to increase the statistical power of the study. This will not only aid in the identification of genomic regions in which the disease gene lies, but will also assist in "fine mapping" studies which aim to reduce the region of DNA linkage to a manageable size of about 1 million bases. Once a region is well defined, we can begin to select candidate genes for mutation testing.

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Sequencing the Dog Genome - The first published sequence of the dog genome was completed in 2003 in an effort lead by Ewen Kirkness at The Institute for Genome Research. Genomes are typically sequenced in many thousands of overlapping segments, and to ensure that the whole genome is recorded at least once, it is estimated that there have to be seven or eight iterations, or "reads," across the entire genome. The 2003 genome, from a standard poodle, was a so-called survey sequence. The genome was sequenced just 1.5 times, so about 80 percent of the genome was present in the final data set. This work was followed shortly thereafter by the release of the draft assembly of the boxer genome, led by Kerstin Lindblad-Toh and colleagues at the Broad Institute, which was done at 7.5x density. With millions of reads successfully completed, nearly 99 percent of the genome is present in the final data set.

Both resources have proved to be extremely useful. The 1.5x sequence provided the first glimpse into the organization of the dog genome, number of genes and organization of repeat elements. One surprise was the discovery of a large number of short interspersed nuclear elements (SINEs) littered throughout the dog genome that were occasionally located at positions with the potential to affect gene expression. For example, the insertion of a SINE element into the gene encoding the hypocretin receptor, a neuropeptide hormone found in the hypothalamus of the brain, results in the disease narco­lepsy in the Doberman pinscher. Similarly, a SINE element inserted into the SILV gene (known to be related to pigmentation) is responsible for merle, the mottled patterning of a dog's coat.

The 7.5x female boxer sequence spans most of the dog's 2.4 billion bases in a sum total of 31.5 million sequence reads. The sequence is estimated to cover over 99 percent of the eukaryotic genome and provides data for the existence of about 19,000 genes. For about 75 percent of the genes, the homology (amount of similarity arising from shared ancestry) between the dog, human and mouse genome is very high. The majority of genes contain no sequence gaps, which is a great aid to scientists seeking to test particular genes as candidates for diseases.

Over the course of its evolution, the canine genome acquired more than two million SNPs, which are proving invaluable for understanding the role of genetic variation both within and between breeds. Such SNPs, analyzed using DNA chips or bead arrays, will be important for scientists conducting whole-genome association studies aimed at identifying genes that underlie complex traits in the dog. A dog chip with about 127,000 SNPs is currently available, allowing scientists to interrogate the dog genome at several thousand positions simultaneously. When the data from dogs with a given disease, for instance lymphoma, are compared to those from dogs without the disease, we can quickly pinpoint regions of the genome where disease genes are likely to lie.

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The Shape of Things - Our research group, along with others, has been interested for several years in identifying genes that define the differences in body size, shape and appearance between breeds. Dog breeds vary not only in overall body size, but also in leg length, head shape and many other body features, all of which are controlled at least in part at the genetic level. The amount of morphologic variation observed in the dog is reported to surpass that of all living land mammals.

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The first important molecular study aimed at understanding the genetics of canine morphology was done at the University of Utah and led by Gordon Lark and Kevin Chase. The project, termed the Georgie Project in memory of a favored dog, focused on the Portuguese water dog, which is ideal for this type of study because it derives from a small number of founders, largely from two kennels, that came to the United States in the early 1950s. The breed standard permits a significant amount of variation in body size compared with other breeds. The community supporting the project is composed of highly motivated owners and breeders who have sought to improve the health of the breed through collaboration with scientists.

To date, the project has collected DNA from more than 1,000 dogs and has completed a genome-wide scan using more than 500 microsatellite markers on nearly 500 dogs. In addition to family history and medical data, more than 90 measurements have been collected for nearly 500 animals. These were derived from a set of five x-rays taken at the time of initial sample collection. Analysis of these metrics led to the development of four primary principal components (PCs), sets of correlated traits that define Portuguese water dog morphology. It is important to keep in mind that PCs are not genes but traits, and as such, they are susceptible to genetic analysis.

Analysis of the genome scan data and four PCs initially highlighted 44 putative quantitative trait loci (QTLs) on 22 chromosomes that are important for heritable skeletal phenotypes in the Portuguese water dog. QTLs derive from complicated statistical analysis and indicate locations in the genome that contribute coordinately to a particular trait. Of particular interest to us was a locus on canine chromosome 15 (CFA15) that showed a strong association with overall body size. Although this was only one of seven loci hypothesized to play a role in body size in the dog, we chose it as an initial focus because of the strength of the effect and the proximity to a compelling candidate gene.

To find the gene on CFA15, we searched for SNPs in a 15 million-base-pair region and then genotyped the resulting set of markers on all the Portuguese water dogs for which size information was available. The distribution of these markers displayed a single peak close to the insulin-like growth factor-1 gene (IGF1), which is known to influence body size in humans and mice. We investigated IGF1 in detail and showed that 96 percent of Portuguese water dog chromosomes carry one of just two patterns of alleles, which are termed haplotypes. The haplotype associated with small dogs was termed "B" and the one associated with large dogs "I." Portuguese water dogs homozygous for haplotype B—that is, dogs that have the B pattern on both chromosomes—have the smallest median skeletal size, whereas dogs homozygous for I are largest. Dogs that are heterozygous—that is, those with a different pattern on each chromosome—fall between.

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To study the presumably more general role of IGF1 in size differentiation among breeds, we surveyed genetic variation associated with 122 SNPs, spanning the relevant 34 million- to 49 million-base-pair interval of chromosome 15 in 353 dogs representing 14 small breeds and 9 giant breeds. Several lines of evidence pointed to IGF1 as the gene likely to account for small body size in the dogs.

Most notably, we observed a dramatic reduction in heterozygosity in small breeds over the IGF1 gene. These results demonstrate the presence of a selective sweep in this region, showing that IGF1 has been under tight selection by breeders seeking to create ever smaller dogs. In addition, the dominance of a single unique haplotype in our panel of many unrelated small dog breeds, together with its near absence in giant breeds, suggests that the mutation is ancient and likely evolved early in the history of domestic dogs.

Sexual Dimorphism - The Georgie Project is remarkable for the number of putative loci that have been discovered by the initial analysis. In addition to loci for head shape, body size, leg length and a host of other traits, loci have also been described that reportedly control differences in size between the sexes, so-called sexual dimorphism. Sexual dimorphism is observed in almost all mammals including, of course, dogs. The mechanisms for maintaining sexual dimorphism are not well understood. It has been shown that the Sry locus on the Y chromosome plays an important role in sex determination and dimorphism, but this is clearly only a small part of the story.

The study of the Portuguese water dog has filled in some additional pieces of this interesting puzzle. This vignette has its roots in the original observation that a locus on chromosome 15, which may or may not be IGF1, interacts with other genes to make males larger and females smaller.

On average, female Portuguese water dogs are 15 percent smaller then males. Chase, Lark and their colleagues observed that in females, a particular haplotype is dominant for small body size. In males, a different set of variants (another unique haplotype) associated with large overall body size is dominant. The locus on CFA15 interacts with another locus on the X chromosome that is known to escape inactivation, meaning that both copies of the genes in this region are turned on (in most locations on the X, only one copy is active).

Females who are homozygous at the X-chromosome locus and who are also homozygous for the large-size CFA15 haplotype are, on average, as large as large males. However, all females that are heterozygous at the X-chromosome marker are small, regardless of their CFA15 genotype. This result suggests several scenarios for how genes interact to affect major complex traits, such as body size, and suggests a mechanism for the evolution of sexual dimorphism.

Two observations from the study must be accounted for in the development of any model to explain canine sexual dimorphism. The explanation must include a discussion of the reversal of dominant haplotypes between males and females associated with CFA15 locus as well as an explanation for the interaction between the CFA15 and X-chromosome loci.

To address the first question, Chase and his colleagues propose the existence of another sex-specific factor. For example, the CFA15 locus might contain two distinct genes associated with two haplotypes; the so-called Ahaplotype acts in both males and females to upregulate size, while the B haplotype and its associated allelesdo not upregulate size but rather contain another gene that suppresses the up-regulator.

The second phenomenon, heterozygote-specific interaction, could be explained by arguing that the activation of haplotype A's critical upregulator gene requires interaction with a protein produced by the X chromosome.

The data of Chase, Lark and their colleagues are consistent with predictions made in the early 1980s that sexual dimorphism evolves because females secondarily become smaller than males as a result of naturalselection for optimal size. Reduction of female size relative to that of males takes place, according to this hypothesis, through an inhibition of major genes that enhance growth, such as the locus on CFA15.

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A Faster Dog - Studies such as those described above are well designed for understanding complex or multigenic traits. But there remains some "low-hanging fruit" to be harvested in the study of canine morphology—other cases where apparently single genes contribute to major traits of interest. An example is provided by my research group's study of the whippet and a mutation in the gene coding for myostatin, a growth factor that limits the buildup of muscle tissue. In this study we found a new mutation in the myostatin gene, MSTN, and observed that it results in a double-muscled phenotype known as the "bully" whippet.

The typical whippet, a medium-sized sight hound, is similar in appearance to dogs of the greyhound breed and weighs about nine kilograms. Whippets are characterized by a slim build, long neck, small head and pointed snout. Bully whippets, however, have broad chests and an unusually well-developed leg and neck musculature that makes them unattractive to fanciers of the breed.

Using a candidate gene approach, we showed that individuals with the bully phenotype carry two copies of a two-base-pair deletion in the third exon (a gene region that is transcribed to make portions of proteins) of MSTN, with the result that a truncated or mutant protein is produced. These findings were somewhat expected, as the double-muscle phenotype observed in the whippet is reminiscent of what has been reported in mice, cattle and sheep and in a single case in humans, each of which was caused by a mutation in the myostatin gene. The specifics for dogs, however, were useful to the whippet dog community, which is seeking to develop a genetic test that will reduce the number of dogs produced with the bully phenotype.

Interestingly, we also found that individuals carrying only one copy of the mutation are, on average, more muscular than wild-type individuals, as measured by their neck and chest girth as well as mass-to-height ratio. Indeed, we estimated that mutations in myostatin explain approximately 60 percent of the variation in both the ratio of height to weight and neck girth, and 31 percent of the variation in chest size. In addition to the statistically significant differences between dogs that were bully and wild types, dogs who carried one copy of the variant allele were more heavily muscled then their wild-type counterparts, although not nearly as heavily muscled as the bully dogs.

This observation caused us to ask whether dogs that carried one copy of the mutation were faster racers—a success that would likely lead them to be bred more, which in turn could produce bully dogs if two recessive-gene individuals were paired. Careful analysis revealed an association between individuals carrying one copy of the MSTN mutation and racing speed. Dogs that were the faster racers (class A) were more likely to carry the mutation then were dogs that were slower racers (classes B, C and D). Least likely to carry the mutation were dogs that had never raced and were primarily show dogs.

We considered the possibility that the result could be explained solely by the fact that A racers tended to be mated more often to A racers as opposed to B, C, D or nonracing dogs. This tendency would predict a significant amount of population substructure among A racing dogs. Although we demonstrated that some population substructure exists, we were able to show that it did not fully account for the observation that an excess of A racing dogs carried the myostatin mutation compared to dogs that either did not race or were class B, C or D. Indeed, 50 percent of the A racers tested carried the mutation. We did not find the variant in greyhounds or any of the heavily muscled mastiff breeds such as the bulldog.

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Remaining Selective - The advances of the past three years in canine genetics have been enormous. The dog genome has been mapped and sequenced. A host of disease loci have been mapped, and in many cases the underlying mutations identified. Our understanding of how dog breeds relate to one another is beginning to develop, and we have a fundamental understanding of the organization of the canine genome. The issue of complex traits is no longer off-limits. We have begun to understand the genetic portfolio that leads to variation in body size and shape, and even some performance-associated behaviors.

Certainly the next few years will bring an explosion of disease-gene mapping. The genetics of canine cancer, heart disease, hip dysplasia, vision and hearing anomalies have all been areas of intense study, and investigators working on these problems are poised to take advantage of the recent advances described here. Whole-genome association studies are likely to replace family-based linkage studies as a way of finding genes associated with not only disease susceptibility and progression, but morphology and behavior as well.

What will the companion-animal and scientific communities do with this new information? It is certainly hoped that the disease-gene mapping will lead to the production of genetic tests and more thoughtful breeding programs associated with healthier, more long-lived dogs. It will be easier to select for particular physical traits such as body size or coat color, not only because we understand the underlying genetic pathways, but because genetic tests are likely to be made available as quickly as results are published. Finally, canine geneticists will finally have a chance to develop an understanding of the genes that cause both breed-specific behaviors (why do pointers point and herders herd?).

What is far less clear is whether we will come to understand what makes the domestic dog unique to us among all the animals in the mammalian world. We have domesticated dogs to the point that they display loyalty, friendship and companionship. We seek their company and approval and bring them into our homes, often as equal members of our family. We rejoice in their victories and mourn their deaths, often as we celebrate or mourn our own children. Is the genetics that defines this relationship within the dog, within ourselves, or both? None of the studies proposed are likely to answer that question, and perhaps that is okay. The comparative-genome projects of humans and dogs were designed to bring about an understanding of our similarities and differences. Perhaps scientists will have to be satisfied to understand that much, and leave as a mystery the genetic basis of approval, adoration and loyalty. At least for me and my dog, it's enough.

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Origin of the domestic dog

en.wikipedia.org/wiki/Origin_of_the_domestic_dog

The origin of the domestic dog includes the dog's genetic divergence from the wolf, its domestication, and the emergence of the first dogs. Genetic studies show that all ancient and modern dogs share a common ancestry and descended from an ancient, now-extinct wolf population - or closely related wolf populations - which was distinct from the modern wolf lineage. The dog's similarity to the extant grey wolf is the result of substantial dog-into-wolf gene flow, with the modern grey wolf being the dog's nearest living relative. An extinct Late Pleistocene wolf may have been the ancestor of the dog.

The dog is a member of the wolf-like canids. The genetic divergence between the dog's ancestor and modern wolves occurred between 20,000 and 40,000 years ago, just before or during the Last Glacial Maximum (20,000–27,000 years ago). This timespan represents the upper time-limit for the commencement of domestication because it is the time of divergence but not the time of domestication, which occurred later.

One of the most important transitions in human history was the domestication of animals, which began with the long-term association between wolves and hunter–gatherers more than 15,000 years ago. The dog was the first species and the only large carnivore to have been domesticated. The archaeological record and genetic analysis show the remains of the Bonn-Oberkassel dog buried beside humans 14,200 years ago to be the first undisputed dog, with disputed remains occurring 36,000 years ago. The domestication of the dog predates agriculture, and it was not until 11,000 years ago in the Holocene era that people living in the Near East entered into relationships with wild populations of aurochs, boar, sheep, and goats. Where the domestication of the dog took place remains debated; however, literature reviews of the evidence find that the dog was domesticated in Eurasia, with the most plausible proposals being Central Asia, East Asia, and Western Europe. By the close of the most recent Ice Age 11,700 years ago, five ancestral lineages had diversified from each other and were represented through ancient dog samples found in the Levant (7,000 years before present YBP), Karelia (10,900 YBP), Lake Baikal (7,000 YBP), ancient America (4,000 YBP), and in the New Guinea singing dog (present day).

In 2021, a literature review of the current evidence infers that the dog was domesticated in Siberia 23,000 years ago by ancient North Siberians, then later dispersed eastwards into the Americas and westwards across Eurasia. Ancient dog remains dating to this time and place have yet to be discovered to support this hypothesis.

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Canid and human evolution

Six million years ago, towards the close of the Miocene era, the earth's climate gradually cooled. This would lead to the glaciations of the Pliocene and the Pleistocene, which are commonly referred to as the Ice Age. In many areas, forests and savannahs were replaced with steppes or grasslands, and only those species of creature that adapted to these changes would survive.

In southern North America, small woodland foxes grew bigger and better adapted to running, and by the late Miocene the first of the genus Canis had arisen—the ancestors of coyotes, wolves and the domestic dog. In eastern Africa, a split occurred among the large primates. Some remained in the trees, while others came down from the trees, learned to walk upright, developed larger brains, and in the more open country learned to avoid predators while becoming predators themselves. The ancestors of humans and dogs would ultimately meet in Eurasia.

Human hunter-gatherers did not live in fear of nature and knew that they posed a formidable risk to any potential predators. Today, the Ju'wasi people of Namibia share their land with prides of lions. Both species coexist with respect and without fear or hostility in a relationship that may go back to the dawn of modern humans. The lion is a much larger and far more dangerous predator than the wolf. Early modern humans entering Eurasia and first encountering packs of wolves may have been assisted in living among them because of the traditional beliefs of their African ancestors. In historical times, mutual respect and cooperation with canines can be found in the stories and traditions of the indigenous peoples of Siberia, East Asia, North America, and Australia.

They were individual animals and people involved, from our perspective, in a biological and cultural process that involved linking not only their lives but the evolutionary fate of their heirs in ways, we must assume, they could never have imagined.

— Mark Derr

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Divergence from wolves

Genetic studies indicate that the grey wolf is the closest living relative of the dog. Attempting to reconstruct the dog's lineage through the phylogenetic analysis of DNA sequences from modern dogs and wolves has given conflicting results for several reasons. Firstly, studies indicate that an extinct Late Pleistocene wolf is the nearest common ancestor to the dog, with modern wolves not being the dog's direct ancestor. Secondly, the genetic divergence (split) between the dog's ancestor and modern wolves occurred over a short period of time, so that the time of the divergence is difficult to date (referred to as incomplete lineage sorting). This is complicated further by the cross-breeding that has occurred between dogs and wolves since domestication (referred to as post-domestication gene flow). Finally, there have been only tens of thousands of generations of dogs since domestication, so that the number of mutations between the dog and the wolf are few and this makes the timing of domestication difficult to date.

*Note: much more information on site posted.

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Dog type - en.wikipedia.org/wiki/Dog_type

Dog types are broad categories of domestic dogs based on form, function or style of work, lineage, or appearance. Some may be locally adapted dog types (or landraces) that may have the visual characteristics of a modern purebred dog. In contrast, modern dog breeds strictly adhere to long established breed standards, that began with documented foundation breeding stock sharing a common set of inheritable characteristics, developed by long established, reputable kennel clubs that recognize the dog as a purebred.

A dog type can be referred to broadly, as in gun dog, or more specifically, as in spaniel. Dogs raised and trained for a specific working ability rather than appearance may not closely resemble other dogs doing the same work, or any of the dogs of the analogous breed group of purebred dogs.

Names in English - The earliest books in the English language to mention numbers of dog types are from the "Cynegetica" (hunting literature), namely The Art of Venery (1327) by Twiti (Twici), a treatise which describes hunting with the limer (a leashed bloodhound type), the pack of running hounds which included barcelets and brachetz both (scent hounds), and the sighthound, the greyhound. More significant in recording the use and description of various dog types is The Master of Game (circa 1406) by Edward of York, a treatise which describes dogs and their work, such as the alaunt, greyhound, pack scent hounds, spaniel and mastiff used by the privileged and wealthy for hunting purposes. The Master of Game is a combination of the earlier Art of Venery and the famous French hunting treatise Livre de Chasse by Gaston Phoebus (circa 1387). The Book of Saint Albans, published in 1486, a "school" book about hawking, hunting, fishing and heraldry, attributed to Juliana Berners (Barnes), lists dogs of the time mainly by function: "First there is a greyhound, a bastard, a mongrel, a mastiff, a limer, a spaniel, raches (small-to-medium sized scenthounds), kennets (small hunting dogs), terriers, butcher's hounds, dung-heap dogs, trundel tails (lapdogs?) and prick-eared curs, and small ladies puppies that bear away the fleas and diverse small sorts."

Almost 100 years later, another book in English, De Canibus Britannicus by the author/physician John Caius, translated (Fleming) from Latin in 1576, attempted the first systematic approach to defining different types of dogs in various categories, demonstrating an apparent increase in types and population. "English dogs": the gentle (i.e., well-bred) kind, serving game—harriers, terriers, bloodhounds, gazehounds, greyhounds, limers, tumblers and stealers; "the homely kind"; "the currish kind", toys; "Fowling dogs"—setters and spaniels; as well as the pastoral or shepherd types, mastiffs or bandogs and various village dogs. Sub-types describing the function of dogs in each group were also included.

Dog types and modern breeds - "It is important", reminded Ann Rogers Clark and Andrew Brace, "not to claim great age for breeds, though it is quite legitimate to claim considerable antiquity for types of dogs." The attempts to classify dogs into different 'species' show that dog types could be quite distinctive, from the Canis melitaeus of lapdogs descended from ancient Roman pet dogs to the even more ancient Canis molossus, the Molossan types, to the Canis saultor, the dancing mongrel of beggars. These types were uniform enough to appear to have been selectively bred, but as Raymond Coppinger wrote, "Natural processes can produce, could produce, and do produce populations of unusual and uniform dogs, that is, dogs with a distinctive conformation." The human manipulation was very indirect. In a very few cases emperors, monasteries or wealthy hunters might maintain lines of special dogs, from which we have today's Pekingese, St. Bernards and foxhounds.

At the beginning of the 19th century, there were only a few dogs identified as breeds, but when dog fighting was outlawed in England in 1835, a new sport of dog showing began. Along with this sport came rules, written records and closed stud books. Dog fanciers began refining breeds from the various types of dogs in use. Some of the old types no longer needed for work (such as the wolfhound) were remade and kept from extinction as show dogs and other old types were refined into many new breeds. Sometimes, multiple new breeds might be born in the same litter of puppies. In 1873, only 40 breeds and varieties were known; today, there are many hundreds of breeds, some 400 of them recognized by the Fédération Cynologique Internationale (FCI) alone. Dog types today are recognized in the names of Group or Section categories of dog breed registries. Named types of dogs that are not dog breeds are still being used where function or use is more important than appearance, especially for herding or hunting, as with the herding dog types of New Zealand that are described by their exact function (Heading Dog, Huntaway, Stopping Dog, etc. - functional terms, not necessarily breed names).