give a dog a genome -
what is whole genome sequencing?
The genome is the term given to all of the DNA that is needed to make a person, dog or other animal. The canine genome is a vast sequence of 2.4 billion bases, or letters, of DNA.
The DNA which makes up the canine genome codes for around 20,000 proteins which are needed to make the cells, tissues and organs of the body. There are actually only four different letters that make up the DNA code; these are A, T, C and G. We can work out the order of DNA letters making up a genome using a technique known as DNA sequencing.
The first complete human genome sequence was determined in the year 2000. Not long after, the genome of a boxer named Tasha was sequenced. Tasha’s sequence is known as the canine reference sequence.
Why is sequencing the genomes of dogs from different breeds useful?
Dogs, like people, have different appearances and personalities, and these attributes are due to a mixture of what scientists call environmental factors, such as nutrition, exercise, upbringing and so on and genetic factors.
The genetic factors are variants in the canine genome; places where the sequence of DNA differs between individuals. Some variants have no effect on the appearance or function of the body (known as the phenotype). Some variants are neutral, and although may cause a change to a phenotype, such as coat colour, do not negatively affect the function of the body.
Some variants however are deleterious and affect the normal function of the body. These deleterious variants, responsible for an undesirable inherited disorder, can be passed from parent to offspring and are referred to as disease mutations.
Genome sequencing of different breeds of dogs is a hugely important new tool now available to the Animal Health Trust. The genome of each dog contains around 2-3 million variants compared to the canine reference sequence, and by sequencing the genomes of healthy dogs we can start to build up a profile of the variants that make up healthy examples of each breed.
Dogs of the same breed are more likely to share genetic variants than dogs of different breeds, so by sequencing the genomes of dogs of different breeds we will maximise our chances of capturing the majority of the variation within the canine genome.
How will this help the Animal Health Trust find mutations that cause disease?
Once we have built up a database of neutral variants that are present across breeds we can then sequence the genomes of dogs affected by disease.
With the help of some powerful computer analysis we can compare variants in the affected dogs against the database of neutral variants and make a shortlist of candidate variants - variants that are potentially the disease mutation we are trying to find.
The more comprehensive our database of neutral variants is the shorter our list of candidate variants will be and the more quickly we will be able to identify the true disease mutation. This will be true for disease investigations in all breeds, not just those that have been sequenced.
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