all in the genes: how inherited diseases happen

Posted by Dr. Kim Smyth on May 21 2012

Recently, a curious pet parent submitted a very important (and complicated) question: Why are some breeds more prone to inherited disease than others? I’ll do my best to explain, though you’ll have to help me out by recalling that long-forgotten genetics lecture you probably got way back in high school biology class. (Get ready to get technical!)

In pets, as in all living organisms, genetic disorders result from abnormalities in genetic make-up. Some of these abnormalities occur because of spontaneous mutations, but many are passed down from the parent animals. This is the case in many purebred dogs and cats, though mixed breeds are certainly affected as well.

So, how are these genetic defects inherited? This is where it gets a little bit complicated, so we’ll use a Maltese dog named Daisy as an example.

Daisy has 78 chromosomes (which occur as 39 pairs) with about 100,000 genes. Each gene in a pair has a partner on the matching chromosome and each member of the gene pair is called an “allele.” Each of Daisy’s traits (for instance, her brown eye color or her white fur color) has two alleles that influence it. If the two alleles are identical (AA or aa), they are termed homozygous. If they are different (Aa), they are called heterozygous.

If this is all sounding confusing, don’t worry. It’s about to get a little easier!

Now, back to the alleles. Dominant traits are represented by capital letters, and recessive traits are lowercase. Dominant traits need only one copy to be passed on to offspring, whereas recessive traits will need two copies. So using Daisy as an example, if a trait is dominant (like her big brown eyes), both homozygous “AA” alleles and heterozygous “Aa” alleles will pass the trait on to Daisy’s puppies, because only one capital A is needed. However, if the trait is recessive (like blue eyes), only homozygous “aa” alleles will pass on the trait. Aa would be a carrier.

There are four patterns of inheritance, so let’s look at them one at a time:

Autosomal dominant: Only one copy of the gene is needed, and it may be inherited from either parent. Because the trait is apparent in both the parent and the offspring, this kind of disease is easiest to eradicate. Affected animals are simply not used for breeding.

Autosomal recessive: This is the most common mode of inheritance of genetic disease in dogs and cats. Two copies of the gene must be inherited in order for the disease to be passed on. If an animal’s allele is heterozygous (Aa), they are carriers, and can potentially pass on the disease without being clinically affected by it themselves. Because they don’t show signs of disease, breeders do not know that they may pass it on to their offspring.

Sex-linked: In sex-linked cases, the gene in question is located on the X chromosome. Male animals get one X from their mom and one Y from their dad, while females have two X chromosomes. If a female is a carrier for a harmful recessive gene (Xx), she will pass the recessive gene to her daughter, who then also becomes a recessive carrier. However, if she passes it to her son, he will be affected. A good example of this kind of inheritance is the disease hemophilia, which more commonly affects males.

Polygenic inheritance: This occurs when a single trait is controlled by two or more sets of alleles, as well as other environmental factors. Canine hip dysplasia is a great example of this: Because multiple genes are involved, there is no one genetic test that can determine the presence of hip dysplasia in a particular set of parents. This makes it a very difficult disease to eradicate. Even if both parents have hips that look good (or even great) on X-rays, they can still produce offspring with hip dysplasia. Environmental factors, such as weight and work load are also a factor in this disease.

So how do we keep Daisy’s puppies from developing genetically inherited conditions? While there are no guarantees (see polygenic inheritance, above), practicing responsible breeding is a good start. Breeders who are not conscientious of genetic diseases perpetuate these conditions by continuing to breed affected or carrier animals. This is particularly true in cases where close family members are bred (such as Daisy and her brother Doc), as they might be more likely to be carriers. Breeding two carriers increases the chances that the offspring will be affected by the disease.

Thankfully, many breeders take the health of their stock very seriously and choose to breed ethically. Daisy’s breeder could choose to have her genetically tested to check if she is a carrier of some diseases. If she came back as a carrier, or if she was showing signs of a hereditary condition, a good breeder would choose not to breed Daisy, opting instead to breed Doc, whose genetic tests came back clean.

I hope that this explains a bit more about why certain question without generating too much confusion. We are always happy to address policy holder questions, so if there’s something you’ve been wondering, don’t hesitate to ask!