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p53 Database
p53 Structures

The dog ( Canis lupus familiaris ) is a domestic subspecies of the wolf, a mammal of the Canidae family of the order Carnivora. The term encompasses both feral and pet varieties and is also sometimes used to describe wild canids of other subspecies or species. The domestic dog has been (and continues to be) one of the most widely-kept working and companion animals in human history, as well as being a food source in some cultures. The dog is also the first animal from Earth to enter into space and fly into orbit.

The dog has developed into hundreds of varied breeds. Height measured to the withers ranges from a few inches in the Chihuahua to a few feet in the Irish Wolfhound; color varies from white through grays (usually called blue ) to black, and browns from light (tan) to dark ("red" or "chocolate") in a wide variation of patterns; and, coats can be very short to several centimeters long, from coarse hair to something akin to wool, straight or curly, or smooth.

The relationship between human and canine has deep roots. Wolf remains have been found in association with hominid remains dating from 400,000 years ago. Converging archaeological and genetic evidence indicate a time of domestication in the late Upper Paleolithic close to the Pleistocene/Holocene boundary, between 17,000 and 14,000 years ago. Fossil bone morphologies and genetic analysis of current and ancient dog and wolf populations have not yet been able to conclusively determine whether all dogs descend from a single domestication event, or whether dogs were domesticated independently in more than one location. Domesticated dogs may have interbred with local populations of wild wolves on several occasions (so-called introgression).

Canis familiaris is part of the genus Canidae , the family of carnivorous mammals commonly known as canines. It includes dogs, wolves, foxes, coyotes and jackals. Canis familiaris was probably domesticated from the wolf 10-12,000 years ago.
Suppression, selection, and mixing within the wolf gene pool have yielded hundreds of breeds of domestic dog. Dogs are unique among mammalian species in the extent of variation they show in morphological traits such as height, weight, mass, shape, and behaviour, yet within each breed, key traits are inherited within extremely narrow limits. The Chihuahua is less than 30cm at the shoulder; the Irish wolfhound close to a meter. The Pomeranian weighs between 1-3kg; the St. Bernard may weigh 60kg. Dog breeds exist which have been purpose bred for guarding, hunting, herding, driving, pulling, etc. No other mammalian species presents natural variation on a scale to rival these, yet individuals from nearly any breed can be mated to yield fertile offspring.
Given the aggressive breeding programs needed to reproducibly generate animals of distinctive size, shape and behaviour, it is not surprising that purebred dog fanciers have also produced closed breeding populations, characterised by over 400 inherited disorders. Genetic diseases are predicted to occur with high frequency in populations with closed gene pools and in which breeding of close relatives is used to propagate desired traits. Breeds established from a small number of founders and expanded rapidly to meet breeders' and consumers' demands suffer the most. Autosomal recessive and complex traits present the biggest problem as the status of asymptotic carriers may not be suspected until several litters have been produced. This includes diseases such as cancer, heart disease, deafness, blindness, motor neuron disease, skin disorders, and a host of autoimmune disorders, each of which has been difficult to study in humans.
A major goal of the dog genome project is to develop a map that will be useful to the entire scientific community for the purpose of mapping genes causing inherited disease in dogs. It is widely recognised that in many pedigree dog lines diseases run in families. Much of the revolution in human molecular medicine has been catalyzed by the development of the human genetic map, which has allowed genes responsible for human genetic disease to be isolated. The map being produced by the dog genome project will catalyze a similar explosion in veterinary medicine and will allow more effective breeding practices to eliminate many genetic diseases from breeds currently afflicted. Even with this large number of different breeds, the common characteristics of a dog are fit muscles, high endurance, proportional balanced height and weight, and ability to use all five senses to the maximum, including a sixth sense which scientists call an electromagnetic sense that allows dogs to sense tremors and vibrations.

Dogs thrive in small social groups or packs which from their cynomorphic (dog) viewpoint may include humans. Dog packs are characterised by companionate hierarchy , in which each individual has a rank, and in which there is intense loyalty within the group. Dogs thrive in human society because their relationships with humans mimic their natural social patterns. The dog is always aware of its rank relative to other individuals in the group, and an assertive dog may consider itself the alpha animal, while considering its human owner to be subordinate.

Role of p53 gene in canis familiaris

Structure of p53 gene

We have characterized gene dysfunction in a cellular model of spontaneous canine mammary cancer by investigating specific gene defects in SIRT2 and p53 genes for comparative studies among canine tumour-derived cell lines. These genes and their downstream targets are involved in regulating gene silencing, cell cycle progression and prevention of senescence and apoptosis. Canine SIR2 reverse transcriptase–polymerase chain reaction amplicons were most homologous to human SIRT2 and revealed detectable transcripts in all cell lines. Canine SIRT2 contained non-conserved amino acid substitutions, representing mutations or allelic differences and interspecies differences. Sequence differences between individuals in p53 and SIRT2 were found in two cell lines including a stop codon in p53 and substitutions of conserved cysteine residues in the Zn 2+ -binding motif in SIRT2. Mutations in SIRT2 were coincident with expression of the p53 modulator, Wip1; a failure to activate p21/Cip1 and extended G2/M phase. A third cell line appeared to function normally in these two pathways and likely possesses other defects in proliferation-control genes. This data identify potentially important defects in pathways regulated by p53 and SIRT2 that modulate cell proliferation and integrate development, apoptosis and proliferative lifespan. These genes offer promising therapeutic targets, contributing to the transformed/immortalized phenotype in spontaneous canine mammary cancer.