| p53 Database |
|
|
|
p53 Structures |
|
|
|
Mammals |
|
|
|
|
|
|
|
|
| |
|
© 2007 IBI Biosolutions Pvt. Ltd. |
|
|
|
|
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.
|
|