Genetics Basics: Modes of Inheritance
What determines an animal’s genetic makeup?
Inherited traits or disorders are passed down in an animal’s genetic code. This genetic code is found in the animal’s DNA, a long molecule that is present in every cell in the body (see handout "Genetic Basics: Understanding DNA"). The DNA contains thousands of genes. A gene is a specific DNA sequence that leads to the expression of an inherited characteristic. For example, there are genes that determine eye color, coat color, and other body characteristics.
How does an animal inherit a trait?
Inside each cell, the DNA is bound into a unit called a chromosome. Each chromosome contains hundreds or thousands of different genes. Chromosomes are found in pairs within the cell. Each cell contains two separate copies of each gene (alleles). While a human has 46 chromosomes (23 pairs), a cat has 38 chromosomes (19 pairs) and a dog has 78 chromosomes (39 pairs). The exception to this rule is sperm cells and egg cells. During the formation of these reproductive cells, each cell gets only one copy of each chromosome. Therefore, each reproductive cells contains only one copy of each gene.
"When an egg is fertilized by the sperm, the new offspring will receive one chromosome from each parent."
When an egg is fertilized by the sperm, the new offspring will receive one chromosome from each parent. This will result in the offspring’s cells again having paired sets of chromosomes, with two copies of each gene. Each copy of the gene is referred to as an allele. For example, in the eye color gene, there may be a blue allele, green allele, brown allele, or other color. Each animal receives one copy of each allele from his mother and one copy from his father.
With two potentially-different alleles present for each gene, how does the body know which allele to express?
The result of each combination of alleles is determined by a trait’s mode of inheritance. Some alleles are dominant, meaning that only a single copy of that allele is necessary to express the trait. This is referred to as an autosomal dominant trait. Other alleles are recessive, meaning that both alleles must be the same in order for the disorder to be observed. This is called autosomal recessive inheritance.
Some disorders are sex-linked, meaning that they are found on the X chromosome. While females receive two copies of the X chromosome (XX), males only receive one copy of the X chromosome. (Receiving a Y chromosome from their father makes them XY, leading them to be male.) Because males only receive one copy of the X chromosome, they are more likely to demonstrate sex-linked characteristics than females.
What is autosomal dominant inheritance?
For an autosomal dominant disorder, only one copy of a given allele is necessary to produce the trait. If an animal receives an abnormal allele from one parent and a normal allele from the other parent, the abnormal trait will be expressed. Affected animals may express the trait to varying degrees, but all animals who carry a copy of the gene will be affected by the trait. Autosomal dominant genetic disorders are uncommon in breeding, because there are no asymptomatic carriers. All affected animals can be readily detected and removed from breeding programs.
"For an autosomal dominant disorder, only one copy of a given allele is necessary to produce the trait."
Polycystic kidney disease (PKD) in Persian cats is an example of an autosomal dominant trait. In this condition, hereditary kidney abnormalities can lead to premature kidney failure and death. Historically, as many as 50% of Persian cats were affected with this condition. After recognizing that this is an autosomal dominant disorder, meaning that there are no healthy carriers of this condition and any affected cat must have at least one affected parent, careful breeding efforts have now significantly reduced the prevalence of this disease. Initially, cats who were intended for breeding were evaluated by ultrasound; cats who had normal kidneys were suitable for breeding, while cats with abnormal kidneys were not bred. More recently, DNA tests have been developed that can detect affected cats with a simple cheek swab. By not breeding affected cats, breeders have significantly reduced the prevalence of PKD in Persian cats.
How does an autosomal dominant disorder differ from an autosomal recessive disorder?
With an autosomal recessive genetic disorder, an animal must receive two copies of the abnormal gene (one from each parent) in order to show signs of the disorder. In most situations, this occurs when both parent animals are asymptomatic carriers of the disorder.
Because the disorder is recessive, an animal who carries one copy of the abnormal gene and one copy of the normal gene will not show signs of disease. If two parents who are carriers are bred, however, 25% of their offspring will receive two abnormal copies of the gene and thus express the genetic disorder. Another 50% of their offspring will receive one abnormal copy of the gene and thus be genetic carriers of the disorder. Finally, 25% of their offspring will receive two normal copies of the gene and be unaffected.
"Autosomal recessive disorders are more likely to be seen when closely related animals are bred..."
Autosomal recessive disorders are more likely to be seen when closely related animals are bred, such as in the case of purebred dogs and cats. This occurs due to similarities in the genetic makeup of closely related animals. Additionally, autosomal recessive traits are hard to eradicate from the breeding pool. Many carriers show no outward signs of disease, making them difficult to detect. When bred with another carrier, the appearance of genetic disorders in offspring may appear random without an understanding of the factors that result in the expression of a recessive genetic disorder.
One example of a recessive genetic disorder in dogs is progressive retinal atrophy (PRA). A dog who is affected with PRA may have parents who did not develop PRA, but instead served as carriers of the disease. In order to avoid creating offspring with PRA, dogs belonging to high-risk breeds should undergo genetic testing prior to breeding. This testing will determine whether one or both parents are a carrier of the disease. If so, these dogs should be removed from the breeding program to decrease future incidence of PRA.
What is sex-linked inheritance?
Male and female animals differ in their sex chromosomes. A male animal carries one X chromosome (received from his mother) and one Y chromosome (received from his father). A female animal carries two copies of the X chromosome (one from each parent). Because the Y chromosome is dominant, XY animals are male and XX animals are female.
"Sex-linked disorders are genetic disorders that are carried only on the X chromosome."
Sex-linked disorders are genetic disorders that are carried only on the X chromosome. Many of these disorders are recessive disorders, and therefore only show signs if there is not a normal X chromosome to override them. In the case of a male with an abnormal gene on the X chromosome, there is no normal allele present and therefore he will show signs of the disorder. In the case of a female, with two copies of the X chromosome present, there is a higher likelihood of one normal allele being present and therefore females are less likely to show signs of sex-linked diseases.
Females, however, can serve as carriers of sex-linked disorders. If a female carrier of a recessive sex-linked disease breeds with an unaffected male, 50% of her male offspring will be affected by the disease, while 25% of her female offspring will become carriers of the diseases.
Is inheritance always so straightforward?
Unfortunately, no. Some traits are considered to be polygenic traits, associated with a number of genes. Expression of these genes is complex, related to interactions between multiple genes and often environmental factors (such as nutrition, rate of growth, exercise, etc.). These traits are often expressed on a continuum, with animals being more or less affected based on their particular genetic makeup and environment. Elimination of these traits is nearly impossible, but improvements in the overall genetic pool can be made by breeding animals at the more desirable end of the continuum.
One example of a polygenic trait is hip dysplasia. Hip dysplasia is controlled by a number of genetic factors, but there are also environmental factors at play in the development of disease within a given individual. Despite over 50 years of efforts to control hip dysplasia, the condition still remains a problem in many large dog breeds. However, screening tests such as radiographic examinations can be used to help decrease the likelihood and severity of hip
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