Mutations and disease

 

Why do inherited conditions occur?

DNA acts as a set of biological instructions that are stored as a type of code made up of units called bases. There are four different bases found in DNA and these are named adenine (A), guanine (G), cytosine(C) and thymine(T).  Just as a sequence of letters can be used to form words, and words be used to form sentences, so too can the sequences of bases be used to produce the proteins that make up each organism. The sum of a dog’s genetic material can be thought of as a cook book which is split into chapters containing recipes. These recipes are the dog's genes and the letters that makes up each recipe are the bases that make up DNA. Just like a recipe can be used to make a dish of food, a gene can be used to make a protein, a building block of a dog's body. 

Each dog has two versions of every gene, one that it inherits from its mother and one that it inherits from its father.  Copies of these variant genes are made by each parent when they produce sperm or eggs and these are passed on to their children. When these genes are copied to produce the sperm and eggs, errors can occur, creating mutant genes (or incorrect copies of recipes if we maintain our analogy). 

The impact of a mutation

Dogs that inherit a faulty gene will make a copy of the error and can pass it on in turn to their descendants. Just like an incorrectly copied recipe, the impact it can have will depend on the type of error made.  A spelling mistake of a common ingredient in a recipe may have no impact whatsoever, while the changing of a cooking time could have severe consequences.  Similarly a mutant gene may have no apparent effect, or it could cause a serious health problem. 

What type of error can occur?

The most common type of error to occur is when a single base is substituted for another.  Sometimes a base may be deleted, or an extra base may be added or changed.  Regardless of the error, most cells usually repair any accidental changes, but errors that are not corrected in cells that become an egg or sperm will be passed on to any offspring.

The DNA sequence of a gene can be changed in several different ways, including:

Missense mutation

One base pair is changed and the type of amino acid that is produced is different.

Nonsense mutation

One base pair is changed which causes the cell to stop building a protein where the error has occurred.  This results in a shortened protein that may not function correctly, if at all.

Insertion

When one or more bases are added into a region of DNA.

Deletion

One or more bases may be removed from a sequence of DNA.

Frameshift

Each strand of DNA is made of sequences of bases which are “read” in groups of threes, called codons.  Each codon produces one amino acid.  The deletion or addition of one or more DNA bases can change the way in which a gene is “read”, shifting the reading frame along and resulting in a faulty protein.                   

Point

Just one base is changed in a DNA sequence – this may be silent, missense or nonsense.

Silent

A change that occurs still produces the same amino acid as before and has no impact on the protein produced.

Splice site

A change to a number of bases that causes a gene to be incorrectly copied into mRNA during transcription.

Chromosomal translocation

Part of a chromosome that reattaches in the wrong place.

Is a mutation always bad?

Not all sections of DNA code for a gene. In fact, most changes to DNA usually occur in the vast areas of DNA between genes, and so have no effect. Changes to areas that code for genes can sometimes mean that proteins are not made correctly, are produced in the wrong quantitates or not made at all. When a mutation does occur in the areas which produce proteins, it is likely to simply cause a different version of the gene resulting in a different characteristic, which is neither good nor bad (i.e. different hair colour or ear length). It is unusual for these changes to be serious or result in death or disease, but it can occur. 

When can mutant genes cause health problems?

Autosomal dominant condition

A health condition that can occurs when a dog has only one copy of a faulty gene (either inherited from its mother or its father). Many of the more severe autosomal-dominant conditions are generally not passed on to any further offspring because the dog is often too ill to reproduce, or dies before it reaches sexual maturity. For this reason autosomal-dominant conditions are usually quite rare.

Autosomal recessive condition

A health condition that can only occur when a dog has two copies of a faulty gene (inherited from both its mother and father) is known as an autosomal-recessive condition.  Dogs with only one copy of the mutant gene are said to be carriers and are unlikely to show any sign of the disease, but can pass the gene on to their offspring. The mutant genes for autosomal-recessive conditions can be the most difficult to predict, because they can be passed on from generation to generation without being noticed or identified.  As long as the dog also has a healthy copy of the gene to do its normal job, then the mutant gene may never be noticed. Often, there is no way to know that these mutant genes exist, or what they cause, until they are expressed in a dog with two copies.  Every organism, including dogs and humans, are carriers for many autosomal recessive conditions which have been passed from generation to generation without ever being noticed.

Complex inherited disorders

Complex inherited disorders are often caused by a number of different genes and are also influenced by environmental factors, such as diet and exercise. The way in which these conditions are inherited is not straight forward; hence the name complex inherited disorders. 

One allele may increase or decrease the chance of a condition developing, but the impact actually be very slight. Lots of genes may contribute to the risk of a dog developing a condition and have an additive effect.

X-linked inheritance

Each individual has two sex chromosome. Men have an X and a Y chromosome and women have two X chromosomes.  Some conditions result from a mutation on the X chromosome. These conditions don’t usually significantly affect females because they usually have one normal copy of the X chromosome which can counteract the mutated chromosome. Although women may not be affected by X-linked conditions they can still be a carrier. If a male inherits a mutation on the X-chromosome he will develop the condition because he only has one X-chromosome. 

Chromosomal conditions

Rather than a condition being caused by a mutation of a specific gene, chromosomal conditions occur when an individual has too many or too few chromosomes. These conditions are not usually inherited but can occur randomly before or soon after an egg is fertilised.

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