The magic of heredity - DNA, chromosomes, genes
All animals are made up of billions of tiny cells. The nucleus of these
cells contains all the information to regulate the activity of the cell and
therefore the form and function of the particular body tissue, and ultimately
to form the individual animal. This information originally comes from the
parents of the animal, with approximately one half from the mother
and one half from the father.
This information from which
all life develops is in the form of DNA (deoxyribonucleic acid). A gene
is a portion of a DNA molecule, carried on a chromosome. Think of a chromosome
as a long string of genes. Hundreds and even thousands of genes may be
carried on a particular chromosome. Chromosomes occur in pairs in the cell
nucleus, except in the egg and sperm where they occur in half pairs. When
an egg is fertilized by the sperm, the resulting cell from which the animal
will develop has complete pairs again. This is the way in which one half
of the genetic information comes from each parent.
The dog has 78 chromosomes, in 39 pairs, on which approximately 100,000
genes are located. This makes up the animal's genotype. The phenotype is
what you actually see in the animal, and this can be influenced by both environmental
and developmental factors. For example, a dog's size as an adult is determined
partly by his or her genes, but is also influenced by environmental factors
such as its health as a puppy and the food it eats.
Each gene in a chromosome pair has a partner at the same position (or
locus) on the matching chromosome. Each member of a gene pair is called an
allele. A gene can have many alleles within a population but an individual
animal will have only 2 alleles which influence a particular trait.
If the 2 alleles are identical (AA or aa for example), the individual is
homozygous at that locus; if the alleles are different (Aa), then heterozygous.
If the allele is dominant, only 1 copy is required to express the trait;
if recessive then 2 copies. Upper case letters are traditionally used to
represent dominant traits, lower case letters for recessive traits. Thus
for a dominant trait, either AA or Aa will express the particular characteristic,
while for a recessive trait only aa will express the characteristic. The
heterozygote (Aa) will be a carrier - clinically unaffected but able to pass
the harmful allele to the offspring.
Example:
Progressive retinal atrophy (PRA) causes blindness in many breeds. P
represents the dominant allele, and p the recessive allele. Since PRA is
a recessive trait, p is the affected allele, and P the normal allele.
The genotypes PP and pp are homozygous. Dogs with the genotype PP have
normal sight and those with pp are affected.
Pp is heterozygous. These animal have normal sight but are carriers.
They will pass the allele for progressive retinal atrophy to approximately
half their offspring.
Phenotypically, both PP and Pp have normal sight, but their genotype
is different. At this time, as with most recessive disorders, there is no
way to identify carriers (animals with the genotype Pp) until affected offspring
are born.
Sex-linked characteristics are slightly different. Females have a pair
of X chromosomes (XX) while males have 1 X and 1 Y chromosome (XY). Thus
1 dose of a recessive X-linked trait (x) will cause the expression of that
characteristic in a male, while a female with only 1 dose(Xx) will be a
clinically unaffected carrier . The bleeding disorder hemophilia is probably
the best known example of a sex-linked condition.
Defects: inherited or not?
A disease condition or abnormality may be caused by many factors. Some
of these are genetic; that is the disorder is a result of a mutation in
a gene that carries particular information. Some mutations are spontaneous,
such as a mutation caused by toxins consumed by the mother during pregnancy.
An inherited defect is one in which the defective gene has been inherited
from one or both of the parents.
Many conditions that have a well-documented hereditary basis may also
have other causes. For example, there are several forms of hereditary cataracts,
but cataracts may also occur as a result of injury, toxins, or a disease
such as diabetes. In trying to determine whether a disorder is inherited,
your veterinarian will look at many factors, including the age the disorder
becomes evident, whether littermates or other relatives are affected, and
whether the defect is known to occur in that breed. It is very important
that inherited disorders be identified so that information can be relayed
back to the breeder, and on a larger scale, so that breeding programmes
can be designed to reduce or eliminate these debilitating conditions in
dogs.
Patterns
of inheritance
The specific pattern of inheritance
has not been established for many of the disorders that are believed to
be inherited. Where the mode of inheritance is not known, breeds that have
an increased risk relative to other dog breeds are said to have a breed
predisposition for a particular condition.
The following describes known patterns of inheritance.
Autosomal dominant
Only 1 copy of the gene, which may be inherited from either parent, is
required to produce the trait. The parent with the dominant trait will
pass the affected gene to approximately half its offspring, and the trait
will be apparent in both the parent and the affected progeny. These conditions
are uncommon because, as long as it is of early onset (ie becomes apparent
before breeding age is reached), the disorder can be readily eliminated
by avoiding the breeding of affected individuals.
In many instances however, there is incomplete dominance. The trait may
be dominant with variable expressivity, which means that if either parent
is affected, all puppies have a susceptibility to the disorder but not all
will be affected equally. Alternately, a dominant trait may have incomplete
penetrance. If penetrance is 75% for example, only about 3 quarters of the
pups who inherit the trait will express it.
Autosomal recessive
This is the most common mode of inheritance for genetic conditions in
dogs. Progressive retinal atrophy (PRA), which causes blindness in many breeds,
is such a trait. To be affected, the animal must inherit 2 copies of the
gene (genotype pp), 1 from each parent. Dogs with the genotype PP (normal)
or Pp (carrier) will be clinically normal but the carrier will pass the affected
gene to approximately half the offspring. As long as carriers (Pp) are mated
to normal animals (PP), the offspring will be unaffected but some will remain
carriers. If 2 carriers are mated, some of the offspring (approximately
25%) will be affected.
example:
Sire
|
|
Dam
|
Sire
|
|
Dam
|
Sire
|
|
Dam
|
PP
|
X
|
pp
|
PP
|
X
|
Pp
|
Pp
|
X
|
Pp
|
normal
|
|
blind
|
normal
|
|
carrier,
normal
sight
|
both carriers
with
normal sight
|
Pp
|
PP and Pp
|
PP
|
Pp
|
pp
|
all offspring are
carriers with
normal sight
|
all have normal sight
but Pp are carriers
|
normal
|
carriers,
normal
sight
|
blind
|
As long as the frequency of a gene for a recessive disorder remains low
in the population, the particular gene may be passed along for many generations
before by chance 2 carriers are mated and affected individuals are born.
However, the gene frequency may become unusually high due to breeding of
close family members, or because of the "popular sire" effect , where a sire
with a harmful recessive gene is mated frequently because of desirable traits.
Because the recessive gene is carried in the population in outwardly
normal animals, it is very difficult to eradicate these traits. However
the incidence can be reduced by identification of carriers through test
matings or through various tests that have been developed, and the conscientious
use of this information in breeding programmes. Veterinarians, dog breeders,
and breed associations must all work together for substantial progress
to be achieved.
Sex-linked traits
In these traits, the gene is located on the X chromosome. Males have
1 X chromosome from their mother, and 1 Y chromosome from their father,
which carries little information other than maleness. Females have 2 X
chromosomes, 1 each from their mother and father. So if a mother who is
a carrier for a harmful recessive gene (Xx) passes the recessive gene (x)
to her daughter, the daughter will be an unaffected carrier, but her sons
who receive that gene will be affected.
The bleeding disorder hemophilia is the best known of the X-linked traits,
which are uncommon in the dog. Control programmes are possible because
carrier females can be identified through blood screening.
The above-mentioned traits are inherited in a straightforward manner.
Many others are inherited in a more complex fashion. In fact, most traits
that are selected for in the dog are the result of the interaction of many
genes. Modifying genes may influence how other genes are expressed. As mentioned
above, a trait may be dominant, but with incomplete penetrance so that
it is not always expressed. Epistaxis occurs when alleles at one locus
mask the action of another pair of alleles.
Polygenic inheritance
Polygenic traits are controlled by an unknown number of genes. The gene
expression is influenced by a variety of factors including gender, nutrition,
breed, rate of growth, and amount of exercise. These traits are quantitative
traits - that is, there is a wide range within the population. Such traits
include height, weight, character, working abilities, and some genetic defects.
Heritability varies within different breeds and within different populations
of a particular breed.
Because it is virtually impossible to determine the exact genotype for
such traits, it is difficult to control defects with a polygenic mode of
inheritance. The best attempts at control are based on a grading scheme
for identification of the defect and a breed policy of recording and publishing
the results for as many dogs as possible. Canine hip dysplasia is a polygenic
trait that remains a problem in most large breeds of dog, despite efforts
to control this condition dating back to the 1960s. Breed organizations
and veterinarians in various countries have developed control programmes
that rely on radiographic evaluation and a central registry of dogs. Thoughtful
selection by breeders, using this information, has greatly reduced the incidence
of hip dysplasia in those breeds in particular countries.
This
database is funded jointly by the Animal Welfare Unit at the Atlantic Veterinary
College, University of Prince Edward Island, and the Canadian Veterinary
Medical Association.
Copyright
© 1998 Canine Inherited Disorders Database. All rights reserved.Revised: December 15, 2000.
reprinted
with kind permission from:-
Alice
Crook, DVM,Coordinator, Sir James Dunn Animal Welfare Centre, Atlantic
Veterinary College,University of Prince Edward Island, 550 University Ave.Charlottetown,
PEI C1A 4P3
