Downloaded from http://veterinaryrecord.bmj.com/ on April 12, 2015 - Published by group.bmj.com
Letters DOG BREEDING
Investigating inherited diseases in dogs AT the Kennel Club Genetics Centre at the Animal Health Trust (AHT) our aim is to identify mutations that are responsible for canine inherited disease, enabling us to develop DNA tests that can be used as diagnostic tools and to help reduce the number of clinically affected dogs within particular breed populations. Notable success stories to date include identification of causal mutations for episodic falling in the cavalier King Charles spaniel (Forman and others 2012b), hereditary juvenile cataract in several breeds (Mellersh and others 2006b), lens luxation in several breeds (Farias and others 2010), several genetically distinct forms of progressive retinal atrophy across a number of breeds (Mellersh and others 2006a, Downs and others 2011, 2013, Downs and Mellersh 2014), and spinocerebellar ataxia in the Parson Russell terrier (Forman and others 2013). The advent of new sequencing techniques has rapidly increased the rate at which canine inherited diseases can be studied and disease mutations identified. Using whole genome sequencing approaches, it is possible to identify the causal mutations for inherited diseases showing a simple pattern of inheritance using a very small number of cases, and potentially with only a single case. We demonstrated this recently using genome-wide RNA sequencing of a single beagle case of neonatal cerebellar cortical degeneration to identify the causal mutation for the disorder, a DNA test for which is now available at the AHT (Forman and others 2012a). With the availability of these new techniques we are keen to start new collaborations to study inherited canine disorders using either genome-wide association study approaches requiring a minimum of six cases and six controls, or whole genome sequencing approaches requiring DNA or RNA from a single robust case. We are particularly interested in congenital and juvenile/early onset disorders, especially those that have a major impact on quality of life and represent a significant welfare issue for affected breeds. Most investigations can be performed using DNA taken from a simple, non-invasive cheek swabbing procedure. To discuss potential projects, please contact Oliver Forman at the AHT. Oliver P. Forman, Cathryn S. Mellersh, Kennel Club Genetics Centre, Animal Health Trust, Kentford, Newmarket, Suffolk CB87UU e-mail: [email protected] 512 | Veterinary Record | May 17, 2014
References
DOWNS, L. M., BELL, J. S., FREEMAN, J., HARTLEY, C., HAYWARD, L. J. & MELLERSH, C. S. (2013) Lateonset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with a frameshift mutation in C2orf71. Animal Genetics 44, 169-177 DOWNS, L. M. & MELLERSH, C. S. (2014) An Intronic SINE Insertion in FAM161A that causes exon-skipping is associated with progressive retinal atrophy in Tibetan spaniels and Tibetan terriers. PLoS One doi: 10.1371/journal.pone.0093990 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 in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations. PLoS One 6 doi: 10.1371/journal. pone.0021452 FARIAS, F. H., JOHNSON, G. S., TAYLOR, J. F., GIULIANO, E., KATZ, M. L., SANDERS, D. N. & OTHERS (2010) An ADAMTS17 splice donor site mutation in dogs with primary lens luxation. Investigative Ophthalmology and Visual Science 51, 4716-4721 FORMAN, O. P., DE RISIO, L. & MELLERSH, C. S. (2013) Missense mutation in CAPN1 is associated with
spinocerebellar ataxia in the Parson Russell Terrier dog breed. PLoS One doi: 10.1371/journal.pone.0064627 FORMAN, O. P., DE RISIO, L., STEWART, J., MELLERSH, C. S. & BELTRAN, E. (2012a) Genomewide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genetics 13, 55 FORMAN, O. P., PENDERIS, J., HARTLEY, C., HAYWARD, L. J., RICKETTS, S. L. & MELLERSH, C. S. (2012b) Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed. PLoS Genetics doi: 10.1371/journal.pgen.1002462 MELLERSH, C. S., BOURSNELL, M. E., PETTITT, L., RYDER, E. J., HOLMES, N. G., GRAFHAM, D. & OTHERS (2006a) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88, 293-301 MELLERSH, C. S., PETTITT, L., FORMAN, O. P., VAUDIN, M. & ARNETT, K. C. (2006b) Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts. Veterinary Ophthalmology 9, 369-378
doi: 10.1136/vr.g3295
Downloaded from http://veterinaryrecord.bmj.com/ on April 12, 2015 - Published by group.bmj.com
Investigating inherited diseases in dogs Oliver P. Forman and Cathryn S. Mellersh Veterinary Record 2014 174: 512
doi: 10.1136/vr.g3295 Updated information and services can be found at: http://veterinaryrecord.bmj.com/content/174/20/512
These include:
References Email alerting service
This article cites 5 articles, 1 of which you can access for free at: http://veterinaryrecord.bmj.com/content/174/20/512#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Letters DOG BREEDING
Investigating inherited diseases in dogs AT the Kennel Club Genetics Centre at the Animal Health Trust (AHT) our aim is to identify mutations that are responsible for canine inherited disease, enabling us to develop DNA tests that can be used as diagnostic tools and to help reduce the number of clinically affected dogs within particular breed populations. Notable success stories to date include identification of causal mutations for episodic falling in the cavalier King Charles spaniel (Forman and others 2012b), hereditary juvenile cataract in several breeds (Mellersh and others 2006b), lens luxation in several breeds (Farias and others 2010), several genetically distinct forms of progressive retinal atrophy across a number of breeds (Mellersh and others 2006a, Downs and others 2011, 2013, Downs and Mellersh 2014), and spinocerebellar ataxia in the Parson Russell terrier (Forman and others 2013). The advent of new sequencing techniques has rapidly increased the rate at which canine inherited diseases can be studied and disease mutations identified. Using whole genome sequencing approaches, it is possible to identify the causal mutations for inherited diseases showing a simple pattern of inheritance using a very small number of cases, and potentially with only a single case. We demonstrated this recently using genome-wide RNA sequencing of a single beagle case of neonatal cerebellar cortical degeneration to identify the causal mutation for the disorder, a DNA test for which is now available at the AHT (Forman and others 2012a). With the availability of these new techniques we are keen to start new collaborations to study inherited canine disorders using either genome-wide association study approaches requiring a minimum of six cases and six controls, or whole genome sequencing approaches requiring DNA or RNA from a single robust case. We are particularly interested in congenital and juvenile/early onset disorders, especially those that have a major impact on quality of life and represent a significant welfare issue for affected breeds. Most investigations can be performed using DNA taken from a simple, non-invasive cheek swabbing procedure. To discuss potential projects, please contact Oliver Forman at the AHT. Oliver P. Forman, Cathryn S. Mellersh, Kennel Club Genetics Centre, Animal Health Trust, Kentford, Newmarket, Suffolk CB87UU e-mail: [email protected] 512 | Veterinary Record | May 17, 2014
References
DOWNS, L. M., BELL, J. S., FREEMAN, J., HARTLEY, C., HAYWARD, L. J. & MELLERSH, C. S. (2013) Lateonset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with a frameshift mutation in C2orf71. Animal Genetics 44, 169-177 DOWNS, L. M. & MELLERSH, C. S. (2014) An Intronic SINE Insertion in FAM161A that causes exon-skipping is associated with progressive retinal atrophy in Tibetan spaniels and Tibetan terriers. PLoS One doi: 10.1371/journal.pone.0093990 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 in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations. PLoS One 6 doi: 10.1371/journal. pone.0021452 FARIAS, F. H., JOHNSON, G. S., TAYLOR, J. F., GIULIANO, E., KATZ, M. L., SANDERS, D. N. & OTHERS (2010) An ADAMTS17 splice donor site mutation in dogs with primary lens luxation. Investigative Ophthalmology and Visual Science 51, 4716-4721 FORMAN, O. P., DE RISIO, L. & MELLERSH, C. S. (2013) Missense mutation in CAPN1 is associated with
spinocerebellar ataxia in the Parson Russell Terrier dog breed. PLoS One doi: 10.1371/journal.pone.0064627 FORMAN, O. P., DE RISIO, L., STEWART, J., MELLERSH, C. S. & BELTRAN, E. (2012a) Genomewide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genetics 13, 55 FORMAN, O. P., PENDERIS, J., HARTLEY, C., HAYWARD, L. J., RICKETTS, S. L. & MELLERSH, C. S. (2012b) Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed. PLoS Genetics doi: 10.1371/journal.pgen.1002462 MELLERSH, C. S., BOURSNELL, M. E., PETTITT, L., RYDER, E. J., HOLMES, N. G., GRAFHAM, D. & OTHERS (2006a) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88, 293-301 MELLERSH, C. S., PETTITT, L., FORMAN, O. P., VAUDIN, M. & ARNETT, K. C. (2006b) Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts. Veterinary Ophthalmology 9, 369-378
doi: 10.1136/vr.g3295
Downloaded from http://veterinaryrecord.bmj.com/ on April 12, 2015 - Published by group.bmj.com
Investigating inherited diseases in dogs Oliver P. Forman and Cathryn S. Mellersh Veterinary Record 2014 174: 512
doi: 10.1136/vr.g3295 Updated information and services can be found at: http://veterinaryrecord.bmj.com/content/174/20/512
These include:
References Email alerting service
This article cites 5 articles, 1 of which you can access for free at: http://veterinaryrecord.bmj.com/content/174/20/512#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
