Scientists working at the Kennel Club Genetics Centre at the Animal Health Trust have identified a new mutation that causes the blinding condition, Progressive Retinal Atrophy (PRA), in Shetland Sheepdogs.
The discovery of BBS2-PRA is particularly significant as it is the first disease mutation discovered as a direct result of the Give a Dog a Genome project. Launched in 2016, with an initial grant of £50,000 from the Kennel Club Charitable Trust, the project aimed to create the UK’s largest canine genome bank to help generations of dogs. To date, the project has sequenced the entire genomes of 89 dogs from 77 different breeds. These genomes are currently being analysed to help understand which changes in the canine genome are neutral and which have a negative effect on dog health.
Kennel Club Genetics Centr博士博士议会博士（Cathryn Mellersh）的动物健康信托基金会表示：“发现一种造成狗的遗传疾病的新突然令人兴奋，因为它为饲养者提供了减少频率的手段未来几代狗的突变，非常重要，以避免培育临床受影响的狗。
“But the discovery of the mutation that causes BBS2-PRA in Shetland Sheepdogs is particularly exciting because it is the first disease mutation we have discovered as a direct result of our Give a Dog a Genome project.”
Give a Dog a Genome uses new whole genome sequencing technology which has helped make the genetic mutation finding process quicker and more efficient. Prior to this, a lengthy Genome Wide Association Study (GWAS) to identify a region of the genome that harboured the disease mutation, followed by sequencing methods to pinpoint the causal mutation, would have been required. This process required DNA from multiple affected dogs (between 12-20 individuals for a disease like PRA).
Through advances in technology and the Give a Dog a Genome DNA database, the Animal Health Trust was able to compare the DNA of just one Shetland Sheepdog with PRA, with the genomes of other dogs to successfully identify the mutation that causes PRA in this breed.
Rebekkah Hitti-Malin, Research Assistant who lead on the test development in Shetland Sheepdogs, said: “Being able to identify a disease mutation from a very small number of dogs means that we can make a DNA test available much earlier in the process of disease emergence, ideally before the mutation has had the chance to become widespread throughout the breed.
“In turn this means that the mutation can be eliminated from the breed population more quickly, possibly within just a few generations of the DNA test being launched.”
This discovery was made possible by successful collaboration between Animal Health Trust geneticists, the Shetland Sheepdog community who participated in Give a Dog a Genome as well as donating DNA and information about their dogs, the Kennel Club Charitable Trust who co-funded the Give a Dog a Genome project and all the other Give a Dog a Genome breeds whose ‘control’ genomes made this sequencing approach possible.
Marion Withers，滋生卫生协调员为Shetland Sheepdogs说：“当该品种被接受到狗的一个基因组项目学习新形式的PRA时，我们很高兴。我们现在很高兴地了解该研究已经产生了积极的结果，并且已经开发了DNA测试，这将有助于育种者在我们的Shelties中降低这种衰弱条件的发病率，并避免遇险给所有者。
“It has been a pleasure working with the AHT and I would like to thank the team for their support and dedication in working with the breed clubs to achieve this outcome."
The Kennel Club Genetics Centre at the Animal Health Trust hopes this success story is the first of many to arise from Give a Dog a Genome, now that all the genomes have been sequenced.
Cathryn Mellersh博士补充说：“给狗的美丽是它的基因组是它的协作性质。我们无法在没有其他76种品种的基因组的情况下如此迅速发现这种突变 - 现在，正如我们开始新的调查，所以驻地牧羊犬基因组将与其他基因组一起占据自己的位置，帮助我们找到与其他品种不同疾病相关的突变。“
The DNA test for PRA (BBS2) in Shetland Sheepdogs, costing £48, will be available from the AHT DNA Testing Service atwww.ahtdnatesting.co.ukfrom Thursday 5 March 2020, and also from the Animal Health Trust’s stand at Crufts (Hall 3, Stand 55).