Five year reportMarch 2009 - December 2013

Inherited disease within purebred dogs has become headline news in recent years. Strongselection for desired characteristics, and the fact that individual breeds are genetically isolated,means that many breeds of dog have reduced gene pools and lower levels of genetic diversity.An unfortunate consequence of this can be the rapid increase of harmful or damaging disease-associated mutations. Inherited conditions observed in some breeds can lead to substantialwelfare concerns and, as there are believed to be more than five million purebred dogs in theUK alone, the issue of inherited disease justifies close attention.

The Animal Health Trust (AHT), with support from the Kennel Club Charitable Trust and otherfunding organisations, has been investigating the genetic basis of canine inherited disease for20 years. Over the last decade huge advances have been made in the field of canine genetics.These advances started with the development of a comprehensive map of the canine genomeand culminated in the sequencing of the entire genome in 2004. Since then, high densitywhole-genome marker arrays have been developed, enabling scientists to locate and pinpointgenetic mutations much more easily and quickly than was previously possible. This enables theefficient and effective development of diagnostic tests, which will help future generations ofdogs.

The Kennel Club Genetics Centre (KCGC) at the AHT, (a collaboration between the Kennel Cluband the AHT), was formed in 2009. Dr Cathryn Mellersh, an experienced canine geneticist andDr Sarah Blott, an experienced quantitative geneticist co-lead the KCGC. The aim of the Centreis to help dog breeders reduce or eradicate inherited disease from their breeds, through thedevelopment of essential tools, minimising the risk of breeding affected puppies, as well as thedesign of breeding programmes to improve the overall health and welfare of the breed. This inturn aims to safeguard the long term genetic health of breeds, by preserving genetic diversity.

In the first five year funding period, which ended at the end of 2013, the KCGC investigated anumber of inherited diseases for their heritability, mode of inheritance, and prevalence withinthe breed at risk being studied. Whole Genome Scan (WGS) technology was used effectively toidentify regions of the genome linked to specific canine inherited diseases. Subsequent finemapping and sequencing, which included the incorporation of next generation sequencingtechniques, were applied to identify the associated mutations. This led to the development ofgenetic screening tests, to determine affected and carrier dogs, which can be performed withsimple mouth swabs.

The KCGC also introduced new approaches to aid in dog breeding decisions. One major advancebeing the development of estimated breeding values (EBVs), to enable whole dog populationsto be evaluated for inherited disease, even if individuals haven’t been scanned or DNA testedthemselves.

Consideration of the impact on the health and welfare of dogs, but also the willingness andsupport of breeders to provide sufficient data and DNA samples for the investigations, havecontributed greatly to the success of the KCGC so far.

This report highlights the progress and major achievements that have been made by the Centrein the first five year funding period.

Introduction

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The Canine Genetics team, led by Dr Cathryn Mellersh, liaises closely with dog breeders, ownersand veterinarians to identify serious and debilitating clinical disorders that are more prevalent insome breeds than others, and are thus likely to be inherited.

The team investigates the genetic basis of a variety of inherited diseases, but has a particularinterest in inherited ocular and neurological diseases, both of which are clinical strengths of theAHT.

The goal of all of our research projects is to identify the genetic variants associated with theseinherited disorders, and develop DNA tests that dog breeders can use to inform their breedingdecisions and improve the genetic health of future generations of dogs.

The team collects DNA, in the form of buccal cheek swabs, from dogs affected with the various disorders under investigation, as well as from unaffected control dogs of the same breed.

Genome wide association studies (GWAS) are used to identify specific regions of the genomeassociated with the disease being investigated and a variety of state-of-the-art technologies,including next-generation targeted, exome and RNA sequencing techniques are used to pinpointthe precise mutations underlying the disease-risk. Once the causal mutations have beenidentified DNA tests are developed and made available to the public.

DNA samplesSince 2009 the canine genetics team has collected and stored DNA samples from 11,000 dogsfrom 170 different breeds. Nearly one in four of these samples (24%) are from dogs affectedwith a disorder that is presumed to be inherited.

Research success storiesWhen the Kennel Club Genetics Centre (KCGC) was established in 2009 an objective was toundertake five genome-wide association studies per year, with each GWAS being for onedisease in one breed.

We have met this objective, having undertaken GWASs with DNA samples from 1,461 dogs of25 different breeds as well as with DNA from 31 crossbred dogs.

The conditions under investigation across these 25 breeds have included hereditary cataract,progressive retinal atrophy, geographic retinal dysplasia, ataxia, episodic falling, congenitalkeratoconjunctivitis sicca, sebaceous adenitis and steroid responsive meningitis.

Between 2009 and November 2013 we identified ten unique mutations responsible for inheriteddisorders that are known to affect 29 different breeds. This brings the total number ofmutations identified by the Canine Genetics team to 14.

These mutations cause inherited disorders in 30 different breeds, with six of the mutationsbeing found in more than one breed, and six breeds benefitting from more than one DNA test.

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Mutation detection

Mutations identifiedMutations have been identified, and DNA tests developed at the AHT, for:

1. Primary lens luxation (PLL) in 17 breeds

(Australian Cattle Dog, Chinese Crested Dog, Jack Russell Terrier, JagdTerrier, Lancashire Heeler, Miniature Bull Terrier, Parson Russell Terrier,Patterdale Terrier, Rat Terrier, Sealyham Terrier, Tenterfield Terrier,Tibetan Terrier, Toy Fox Terrier, Volpino Italiano, Welsh Terrier, YorkshireTerrier, Wire-haired Fox Terrier).

PLL is a painful and potentially blinding condition. In PLL affected dogs the fibres which supportthe lens within the eye break down or disintegrate, causing the lens to become loose within theeye. If the lens moves to the front of the eye, rapid onset glaucoma and loss of vision can result.

Since the launch of the DNA test in October 2009, close to 12,400 dogs of 15 breeds, from 40different countries, have been tested for the PLL mutation. Of these, 382 have been identified asgenetically affected and almost 400 as carriers.

2. Progressive retinal atrophy (PRA) in Golden Retrievers

Progressive retinal atrophy (PRA) is a well-recognised inherited conditionin many breeds of dog. The condition is characterised by bilateraldegeneration of the retina which causes progressive vision loss thatculminates in total blindness. There is no treatment for PRA - the mostsuccessful way to combat the disease is to identify dogs that carry themutation and develop informed breeding strategies.

In 2010 we developed a DNA test following the identification of the mutation which causes themost common form of PRA among Golden Retrievers in Europe – known as GR_PRA1. Since thelaunch of the DNA test in November 2010, more than 2,600 Golden Retrievers have been testedfrom 16 different countries. Of these, seven dogs have been identified as affected and 184 ascarriers.

In 2012 we developed a second DNA test for PRA in the Golden Retriever, based on a differentmutation we identified that causes a genetically different form of PRA in this breed. We namedthis form of the disease GR_PRA2. The two forms of PRA are clinically identical, but are geneticallydistinct diseases caused by independent mutations. Since the launch of the DNA test in August2012 we have tested over 2,000 Golden Retrievers for the GR_PRA2 mutation; one affected doghas been identified and 213 carriers.

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3. Progressive retinal atrophy in Tibetan Spaniels and TibetanTerriers

In 2013 our geneticists discovered a mutation that causes a different formof progressive retinal atrophy (PRA) in Tibetan Spaniels and TibetanTerriers. We are calling this form of the disease PRA3 to distinguish it fromother, genetically distinct, forms of PRA that are caused by differentmutations, including the rcd4 mutation that is also known to cause PRA insome Tibetan Terriers (described below).

Since the launch of the PRA3 DNA test in July 2013 we have tested more than 780 dogs, of whichtwo have been identified as affected with PRA and 47 of which are carriers.

4. Late-onset progressive retinal atrophy (PRA) in Gordon andIrish Setters and Tibetan Terriers

Gordon Setters suffer from a late onset form of PRA that doesn’t typicallyaffect dogs until they are around eight years of age. Owners report thattheir affected dogs develop night blindness in the first instance, which isindicative of a rod-cone degeneration, so we have termed this mutationrcd4 (for rod-cone degeneration 4) to distinguish it from other, previouslyidentified, forms of rod cone degeneration.

We have identified the mutation for rcd4, which we believe is the most common form of PRA inthe Gordon Setter, but our investigations indicate that there might be another, genetically distinct,rarer form of PRA in this breed. The rcd4 mutation is also present in Irish Setters and TibetanTerriers.

Since the launch of the DNA test in March 2011, we have tested more than 5,100 dogs from 23different countries for the rcd4 mutation. Of these, 415 dogs have been identified as affected andmore than 1,900 as carriers.

5. Curly coat and dry eye (CCDE) syndrome, and episodic falling(EF) in Cavalier King Charles Spaniels

Curly coat and dry eye (CCDE) syndrome, known scientifically ascongenital keratoconjunctivitis sicca and ichthyosiform dermatosis, affectsa dog’s eyes and skin. Affected dogs produce no tears making their eyesincredibly sore. Their skin becomes very flaky and dry, particularly aroundthe foot, and this can make standing and walking difficult and painful. Thissyndrome appears to be a problem unique to Cavalier King CharlesSpaniels (CKCS) and most dogs diagnosed with the condition are put to sleep.

© Diane Pearce

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Episodic falling is a neurological condition, induced by exercise, excitement or frustration, in whichmuscle tone increases. During an episode an affected dog is unable to relax its muscles, becomesrigid and often falls over. Affected dogs usually start to demonstrate clinical signs before oneyear of age, with most cases having their first episode aged four to seven months. We identifiedthe mutation for EF at the same time as we found the mutation for CCDE (above), and a DNAtest has been developed that screens for both mutations simultaneously.

Since the launch of the DNA test in April 2011, we have tested over 6,500 CKCS from 15different countries for both mutations. Of these, 203 dogs have been identified as affected withEF, five as affected with CCDE and more than 1,800 dogs as carriers of either EF or CCDE.

6. Late onset ataxia in the Parson Russell Terrier

Late onset ataxia (LOA) in the Parson Russell Terrier (PRT) is a disease ofincoordination of gait and lack of balance. The onset age for the disease isusually between six months and one year of age, when owners may startto notice that their dog is showing changes in gait pattern, (often weavingof the hind limbs), and some difficulty balancing. The disease isprogressive and affected dogs become increasingly uncoordinated withdifficulty balancing, which makes moving around and everyday tasks suchas going up and down stairs difficult. There is no treatment or cure for LOA and affected dogs areoften euthanized, typically around two years after onset, on humane grounds, as their quality oflife diminishes.

We undertook extensive investigations of LOA in the PRT and successfully identified the mutationresponsible for the disease.

In November 2012 we developed a DNA test, based on this mutation, and since that time we havetested more than 1,500 PRTs, of which 20 are affected and 230 are carriers.

7. Neonatal cerebellum cortical degeneration in the Beagle

Neonatal cerebellar cortical degeneration (NCCD) is a hereditary diseasethat can affect Beagle puppies. Affected puppies start showing clinicalsigns around three weeks of age. They are slower and less coordinatedthan their littermates, fall more often and are unable to regulate anormal gait. This disease has minimal progression, but currently there isno cure. The clinical signs are due to damage in their cerebellum, whichis the part of the nervous system that controls the movement and theequilibrium.

In 2012, together with the AHT’s own veterinary neurologists, a novel technique was used toidentify the mutation for NCCD in the Beagle and make a DNA test available.

Since the launch of the test over 250 Beagles have been tested, of which 14 are carriers.

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© Vigor Beagles

8. Cerebellar ataxia in the Italian Spinone

Cerebellar ataxia (CA) in the Italian Spinone is a serious neurologicaldisease. In affected dogs the cerebellum, which is the part of the brainresponsible for the co-ordination of motor movement in the body,becomes diseased. Affected dogs are born normal, but clinical signs,which include the development of an unsteady gait, loss of co-ordinationand poor balance usually appear within the first weeks or months of life.The disease is progressive; symptoms worsen during the first year of thedog’s life such that most dogs are euthanased before they are one year old. There is notreatment for the disease, which has an autosomal recessive mode of inheritance.

In 2008 we identified the region of the genome that contained the CA mutation and developeda linkage-based DNA test for the disease which we estimated gave an accurate result forbetween 95% and 98% of dogs tested.

Since its launch we have tested 574 Spinone, of which 35 were carriers. The test has been usedby Spinone breeders to effectively eliminate the condition from the breed in the UK and, as faras we are aware, no affected dogs have been born since the test was launched. Recently weidentified the precise mutation responsible for CA in the Italian Spinone and a manuscript iscurrently being prepared for publication.

Additional DNA tests offered by the Animal Health TrustApart from the DNA tests based on the 14 mutations identified by geneticists from the KCGC,the AHT offers DNA tests for 12 additional inherited disorders to around 20 additional breeds.The AHT’s DNA testing facility tests around 12,000 dogs each year. (Overall, canine samplessubmitted for DNA testing in 2013 were up 11% on numbers for 2012.) A full list of the canineDNA tests we offer can be found on our website (www.aht.org.uk/dnatesting).

DNA testing statisticsThe AHT DNA testing facility has tested over 38,000 dogs for the 10 mutations that we haveidentified between 2009 - 2013, and over 67,000 dogs for all 14 mutations that the geneticsteam have identified.

More than 14,000 of the dogs tested have been found to be carriers of at least one disease-associated mutation; as all the mutations are recessive a DNA test is the only way to reliablyidentify carriers prior to breeding, and the carrier status of most of these dogs would thereforehave been indiscernible before the development of these DNA tests.

PhD success storyFour of the mutations identified are responsible for genetically distinct forms of progressiveretinal atrophy, (an incurable disease that leads to total blindness).

The four mutations, which segregate in the Golden Retriever (two mutations), the Gordon andIrish Setter, the Tibetan Spaniel and the Tibetan Terrier (two mutations) were identified byLouise Downs and the work formed the basis of her PhD thesis, which she successfullydefended in October 2013.

The KCGC is thus enabling research that both improves the genetic health of future generationsof purebred dogs, but also contributes to the training of future generations of scientists.

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Table 1

The tables below list the number of DNA tests performed during the period 2009-2013,indicating those tests for which the causative mutation was identified by the Kennel ClubGenetics Centre (Table 1) and those for which the causal mutation was identified by the CanineGenetics research group at the AHT, prior to the establishment of the Kennel Club GeneticsCentre (Table 2).

Table 2

DNA testing at Animal Health Trust (2009-2013)

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Disorder Abbreviation Breed(s) Number of Tests Performed

Progressive retinal atrophy GR_PRA1 Golden Retriever 2,655

Progressive retinal atrophy GR_PRA2 Golden Retriever 2,023

Progressive retinal atrophy RCD4 Gordon and Irish Setters, Tibetan Terriers 5,130

Progressive retinal atrophy PRA3 Tibetan Spaniels and Tibetan Terriers 781

Episodic falling EF Cavalier King Charles Spaniel 6,573

Curly coat dry eye syndrome CCDE Cavalier King Charles Spaniel 6,573Neonatal cerebellar cortical

degeneration NCCD Beagle 258

Late onset ataxia LOA Parson Russell Terrier 1,526

Primary lens luxation PLL Various breeds 12,368

Cerebellar ataxia CA Italian Spinone 574

38,461

Disorder Abbreviation Breed(s) Number of Tests Performed

Hereditary cataract HC Staffordshire Bull Terriers, French Bulldogs, Boston Terriers 8,234

Hereditary cataract HC Australian Shepherds 3,322

Cone-rod dytrophy CORD1 Miniature Longhaired Dachshunds and English Springer Spaniels 8,619

L-2-Hydroxyglutaric aciduria L-2-HGA Staffordshire Bull Terriers 8,463

28,638

Quantitative Genetics

Research carried out by the Quantitative Genetics team aims to develop effective methods ofgenetic evaluation for complex diseases, as management of these diseases poses the greatest challenge to dog breeders. Of the 489 currently known genetic diseases in dogs, 72% arebelieved to be complex (http://omia.angis.org.au).

The Quantitative Genetics team also aims to develop breeding strategies for canine populationsthat will maintain long-term health by managing rates of inbreeding, while reducing theprevalence of existing disease; and to encourage the implementation of state-of-the-artbreeding techniques in dog breeding by developing Internet-based tools for breeders.

Development of Mate SelectThe Quantitative Genetics team worked with Kennel Club IT developers to implement thealgorithm for calculating inbreeding coefficients for all KC registered dogs, and for prospectivematings.

Phase one of Mate Select, launched in May 2011, enables breeders to:

• access a dog’s individual inbreeding coefficient

• access the average inbreeding coefficient for any breed recognized by the KC

• perform hypothetical matings and predict the inbreeding coefficients of the puppies.

This service now attracts more than 23,000 searches per month (statistic measured in 2012).

We are now creating technologies that will underpin the second and third phases of MateSelect. This includes developing statistical models, so EBVs for conditions such as hip and elbowdysplasia can be calculated. We are also researching the impact of ‘optimum contributions’(OCs) when applied to dog breeds.

By using OCs we will be able to understand the impact that using any particular dog will haveon the future diversity of a breed.

Going forward, once all three tools are operational, we will continue to carry out the routinecalculation of EBVs and OCs ensuring the data breeders are accessing is as accurate and up-to-date as possible. We also hope that through our continued research we will be able to developnew features for the program, ensuring that Mate Select remains an innovative and cutting-edge development in dog breeding.

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Estimated breeding values (EBVs)Complex diseases, such as hip dysplasia and epilepsy, are believed to be caused by acombination of genetic and environmental effects. Pedigree information and population-widedata on disease, such as that collected for the BVA/KC health screening schemes, are analysedusing advanced statistical techniques to calculate the extent to which a disease is genetic (itsheritability), and this information is used to determine EBVs. EBVs are an objective numericalassessment of the genetic status of an individual dog, with environmental effects removed. Byusing EBVs breeders can distinguish between dogs of high and low genetic risk when selectingparents.

The research required to establish heritabilities for hip and elbow dysplasia and to developappropriate statistical models for EBVs has been carried out. The results have been published insix peer-reviewed papers. EBVs for hip score in 15 breeds and elbow score in five breeds havebeen developed.

The breeds are: Labrador Retriever, Golden Retriever, German Shepherd Dog, Rottweiler, BorderCollie, Flat Coat Retriever, Bernese Mountain Dog, Newfoundland, Siberian Husky, BeardedCollie, English Setter, Gordon Setter, Akita, Tibetan Terrier, Rhodesian Ridgeback.

These breeds encompass more than 80,000 KC registrations per year, so that EBVs will initiallybe available for about 33% of all KC registered dogs.

An informative display has been developed for EBVs in Mate Select. For example, the accuracyof the EBV is reflected graphically using a feathered bar to represent the probability densityaround the EBV (Figure 1). This will ensure that breeders take account of both the EBV and itsaccuracy in the comparison of dogs.

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Figure 1: Example of graphical display of EBVs in Mate Select. The results for two different dogs are shown, showing both their hip and elbow score EBVs.The EBV is shown as a circle on a coloured bar, the shading around the circle indicates theaccuracy of the EBV. The breed average is represented by the vertical line in the middle of thebar. EBVs which are lower risk than average fall in the green area and those at higher risk thanaverage in the red area.

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Higher Risk Breed Average Lower Risk

100120 80 60 40 20 -100 -120-80-60-40-20

Score EBV Accuracy

- 17 60%Elbow

Higher Risk Breed Average Lower Risk

100120 80 60 40 20 -100 -120-80-60-40-20

- -14 70%Hip

Higher Risk Breed Average Lower Risk

100120 80 60 40 20 -100 -120-80-60-40-20

Score EBV Accuracy

- 45 92%Elbow

Higher Risk Breed Average Lower Risk

100120 80 60 40 20 -100 -120-80-60-40-20

1/0 = 1 -38 98%Hip

The main benefits of introducing EBV to UK dog breeding have been described by Lewis et al. (2013). The possibility of international collaboration to generate EBV relevant acrossinternational populations has also been investigated.

Fikse et al. (2013) have demonstrated the fulfilment of two important pre-requisites forinternational collaboration to be of benefit: 1) there has been substantial migration of dogsbetween the UK and other countries in at least four breeds studied (Labrador Retriever, GoldenRetriever, Flat Coat Retriever and Bearded Collie) and 2) EBV for hip dysplasia in the UK andEurope are strongly and favourably correlated, despite differences in screening methods.

Heritability analyses were carried out for syringomyelia and mitral valve disease (MVD) in theCavalier King Charles Spaniel. The production of routine EBVs for these conditions requiressuitable screening and data collection procedures to be in place. A new KC/BVA scheme forsyringomyelia, open to all breeds, has been launched.

Dog A.

Dog B.

Inbreeding and population analysesInbreeding is one of the risk factors for inherited disease in purebred dogs. It is important tounderstand how the population structure of breeds may be contributing to an increased rate ofinbreeding. Analysis of the population structure and rate of inbreeding for all 211 Kennel Clubrecognised breeds is currently underway.

Population analyses have been completed for 132 breeds. There are a further 49 breeds withmore than 100 total registrations and mean number of registrations per year of at least 20, forwhich analyses will be attempted.

The mean effective population size, calculated for 127 breeds, was 93 with a minimum of 14(Cesky Terrier) and a maximum of 1,673 (Australian Shepherd). Five breeds had a declining rateof inbreeding meaning the effective population size is increasing.

Figure 2 shows the distribution of breed effective population sizes. Approximately 40% of thebreeds analysed have effective population sizes below 50, which is the minimum sizerecommended in order to manage the effects of inbreeding and maintain a viable population.

Figure 2: frequency distribution (histogram) and cumulative distribution of effectivepopulation sizes in the sample of 127 breeds.

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Summary

The Kennel Club Genetics Centre at the AHT has made outstanding progress since its launch in2009. The initial vision of combining the resources and expertise of the Kennel Club and theAnimal Health Trust to create one centre of excellence, aimed at promoting the health andwelfare of dogs – both individuals and whole breeds – has proven extremely successful.

There is still much to achieve, therefore it is tremendous news that the Kennel Club CharitableTrust have provided a further five years of funding to continue this important work. We willcontinue to take full advantage of new and developing technologies to discover more mutations,in the hope that they will lead to the development of further DNA screening tests that breederscan use to control, or even eliminate, painful and devastating diseases.

We will also continue to advance the tools available to dog breeders, particularly for dealingwith the risk of complex diseases. This will include expanding the range of complex diseases forwhich EBVs are available, and researching new methods for calculating genetic risk. We will alsobe testing breeding strategies aimed at improving canine health, and diminishing the impact ofinherited disease, using computer modelling.

Through publications, articles and seminars we will continue to update dog owners andbreeders on progress, as well as advise them on available tests and appropriate breedingstrategies, aimed at minimising disease risk specifically for their breeds.

We are committed to helping dog breeders in the UK, and across the world, to produce happyand healthy puppies. We are confident that breeders will continue to make the most of thescientific developments that we are generating, to ensure we are all able to achieve thisimportant goal.

Acknowledgements

We would like to thank all the breed clubs, societies, individuals and veterinary surgeons - bothat the AHT and at other practices - who have helped fund and contribute to our progress andachievements. Without your support, information and samples, we would not have been able toproduce the DNA tests and diagnostic tools that we have developed over the last five years.On many of the individual projects, within the KCGC at the AHT, we have collaborated withscientists and veterinary professionals working elsewhere. These include:Dr David Sargan (Cambridge University), Dr David Gould (Davies Veterinary Specialists),Professor John Woolliams (The Roslin Institute and the Royal Dick School of VeterinaryMedicine), Professor Jacques Penderis (University of Glasgow School of VeterinaryMedicine) and Professor Brian Kinghorn (University of New England, Armidale, Australia).

We are grateful for additional funding from The WALTHAM Foundation, the PetPlan CharitableTrust, and the LUPA project (www.eurolupa.org.uk).

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The research undertaken by the KCGC has resulted in the following publications, with anadditional manuscript in press and two more in preparation:

Forman, O. P., De Risio, L. & Mellersh, C. S. (2013) Missense Mutation in CAPN1 Is Associatedwith Spinocerebellar Ataxia in the Parson Russell Terrier Dog Breed. PLoS ONE, 8, e64627.

Sanchez-Molano E, Woolliams JA, Blott SC, Wiener P. (2013) Assessing the impact of genomicselection against hip dysplasia in the Labrador retriever. Journal of Animal Breeding andGenetics, Oct 18. E-pub ahead of print.

Lewis TW, Blott SC, Woolliams JA. (2013) Comparative analyses of genetic trends and prospectsfor selection against hip and elbow dysplasia in 15 UK dog breeds. BMC Genet. Mar 2; 14: 16.Highly accessed: 1,585 views.

Fikse WF, Malm S, Lewis TW. (2013) Opportunities for international collaboration in dogbreeding from the sharing of pedigree and health data. Vet J. 197: 873-875.

Forman, O. P., Penderis, J., Hartley, C., Hayward, L. J., Ricketts, S. L. & Mellersh, C. S. (2012)Parallel Mapping and Simultaneous Sequencing Reveals Deletions in BCAN and FAM83HAssociated with Discrete Inherited Disorders in a Domestic Dog Breed. PLoS Genetics, 8,e1002462.

Miyadera, K., Kato, K., Boursnell, M., Mellersh, C. S. & Sargan, D. R. (2012) Genome-wideassociation study in RPGRIP1 (-/-) dogs identifies a modifier locus that determines the onset ofretinal degeneration. Mammalian Genome, 23, 212-23.

Mellersh, C. (2012) DNA testing and domestic dogs. Mamm Genome, 23, 109-23.

Forman, O. P., De Risio, L., Stewart, J., Mellersh, C. S. & Beltran, E. (2012) Genome-wide mRNAsequencing of a single canine cerebellar cortical degeneration case leads to the identification ofa disease associated SPTBN2 mutation. BMC Genetics, 13, 55.

Downs, L. M., Bell, J. S., Freeman, J., Hartley, C., Hayward, L. J. & Mellersh, C. S. (2012) Late-onset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with aframeshift mutation in C2orf71. Animal Genetics.

Downs, L. M., Wallin-Hakansson, B., Boursnell, M., Marklund, S., Hedhammar, A., Truve, K.,Hubinette, L., Lindblad-Toh, K., Bergstrom, T. & Mellersh, C. S. (2011) A Frameshift Mutation inGolden Retriever Dogs with Progressive Retinal Atrophy Endorses SLC4A3 as a Candidate Genefor Human Retinal Degenerations. PLoS ONE, 6, e21452.

Mellersh, C. (2011) DNA testing man's best friend. Veterinary Record, 168, 10-2.

Gould, D., Pettitt, L., Mclaughlin, B., Holmes, N., Forman, O., Thomas, A., Ahonen, S., Lohi, H.,O'leary, C., Sargan, D. & Mellersh, C. (2011) ADAMTS17 mutation associated with primary lensluxation is widespread among breeds. Veterinary Ophthalmology, 14, 1-7.

Woolliams JA, Lewis TW, Blott SC. (2011) Canine hip and elbow dysplasia in UK Labradorretrievers. Vet J. 189: 169-176. Review.

Published papers

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Lewis TW, Ilska JJ, Blott SC, Woolliams JA. (2011) Genetic evaluation of elbow scores and therelationship with hip scores in UK Labrador retrievers. Vet J. 189: 227-233.

Farias, F. H., Johnson, G. S., Taylor, J. F., Giuliano, E., Katz, M. L., Sanders, D. N., Schnabel, R.D., Mckay, S. D., Khan, S., Gharahkhani, P., O'leary, C. A., Pettitt, L., Forman, O. P., Boursnell, M.,Mclaughlin, B., Ahonen, S., Lohi, H., Hernandez-Merino, E., Gould, D. J., Sargan, D. & Mellersh,C. S. (2010) An ADAMTS17 Splice Donor Site Mutation in Dogs with Primary Lens Luxation.Investigative Ophthalmology and Visual Science, 51, 4716-4721.

Lewis TW, Woolliams JA, Blott SC.(2010) Optimisation of breeding strategies to reduce theprevalence of inherited disease in pedigree dogs. Animal Welfare. 2010; 19(S): 93-98.

Lewis TW, Woolliams JA, Blott SC. (2010) Genetic evaluation of the nine component features ofhip score in UK Labrador Retrievers. PLoS One 5(10): e13610. 1,208 views, 8 citations.

Lewis TW, Blott SC, Woolliams JA. (2010) Genetic evaluation of hip score in UK Labrador Retrievers.PLoS One 5(10): e12797, 3,037 views, 13 citations.

Lewis T, Swift S, Woolliams JA, Blott S. (2010) Heritability of premature mitral valve disease inCavalier King Charles spaniels. Vet J. 188: 73-76.

Lewis T, Rusbridge C, Knowler P, Blott S, Woolliams JA. (2010) Heritability of syringomyelia inCavalier King Charles spaniels. Vet J. 183: 345-347.

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AHT registered charity no: 209642