American Spaniel Club Foundation, Inc.

Health and Research

Current Size: 100%

BREAKING NEWS!!!  

AMERICAN SPANIEL CLUB FOUNDATION WEBINAR

Date and Time Wednesday 07/12/2017 5:00 PM US/Pacific (GMT-0700)

SUBJECT:  One hour presentation and Q&A discussion with Dr. Aguirre on the Cocker Spaniel Cataract Study at University of Pennsylvania. 

SUGGESTION:  To get the most from this webinar – please read the written report from Dr. Aguirre’s team before attending.   The purpose of the webinar is to add more detail to the document and you will benefit from a prior reading.   http://asc-f.org/content/health-and-research

FORMAT:  One hour presentation and discussion.  

        Approximately a 30 minute presentation and 30 minute Q&A discussion by Dr. Aguirre hosted by ASC Foundation (C.Born)

        Questions should be submitted before the webinar. 

        Please submit questions you would like addressed to cborn89052@gmail.com by July 10 using the Subject: ASC Webinar.   

        Post webinar – session will be recorded and will be available along with PDF of presentation materials within a week.

INSTRUCTIONS:  The webinar will be one hour long.  At the scheduled date and time of the meeting, you need to do two things. 

1. To hear the audio - Dial In to the Conference (United States): (605) 472-5683

Access Code: 761371

International Dial-in Numbers: If dialing in from outside the US here is a list of alternative numbers you can use.   https://www.freeconferencecall.com/wall/ascfoundation#international

2. Join Online Meeting: To see the presentation as it’s given

Online Meeting Link: https://join.freeconferencecall.com/ascfoundation

Online Meeting ID: ascfoundation

Research Update

I am pleased to share with you the mid-year progress report in its entirety from Dr. Aguirre/University of PA cataract study.  As you know this study is underwritten by the ASC Foundation with your contributions.   The report is long and detailed and you should read it carefully.  

Mark your calendars for an online Webinar with Dr. Aguirre on Wednesday July 12 at 8PM ET where he will give some further depth and color to this report for us and also be available for Q&A.    Watch further communications from me on details and process.

 On behalf of the ASC Foundation Board, thank you for your support and contributions to this study to date.   We share with you a sincere hope that we can find that genetic marker for cataracts in our beloved Cockers.

Charles Born, ASCF Communications Chair  

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Progress Report:                                                         May 31, 2017 

 Molecular Genetic Studies of Inherited Cataracts in the American Cocker Spaniel  

Personnel: 

University of Pennsylvania 

Gustavo Aguirre, VMD, PhD; Principal Investigator 

Leonardo Murgiano, PhD; Post-doctoral fellow and Project Scientist 

(Doreen Becker, DVM, PhD; Post-doctoral fellow and former Project Scientist)

Jessica Niggel, M.Sc., Research scientist 

OptiGen, LLC 

Susan Pearce-Kelling, BS, MS; Research manager 

Aušra Milano, PhD; Research scientist

 

Objectives: 

Cataracts are the most common cause of vison impairment in humans and are often observed in animal models such as mice, sheep, cattle and swine. They are also one of the most frequent ophthalmic diseases, as well as a major cause of blindness in dogs, affecting both mixed and pure breeds. The American Cocker Spaniel (ACS) breed is one of the most frequently affected. According to the ACVO “Blue Book” (2014 edition), ACS cataract prevalence ranges from 8.77% to 11%. However, this number includes both acquired and inherited cataracts, where the latter category contains cataract phenotypes that are clinically similar, but may have a different genetic etiology and only a superficial clinical similarity. ACS dogs with inherited cataracts are born with normal lenses, which then proceed to opacify over time, leading to blindness by 2-10 years of age. The mode of inheritance in ACS has been proposed to be autosomal recessive and there are no gene-based tests available. Our project focuses on the identification of gene(s) causing the most common form of cataract in ACS and on validating its inheritance mechanism. Once the gene and mutation is recognized, ‘atypical cases’ will be included in further analyses. 

 

Background: 

Cataracts are often an inherited condition, characterized as any opacity/cloudiness of the lens, which may impair vision or cause blindness. The opacities may vary in size, shape, localization, age of onset, progression rate and cause. They usually arise due to lens protein misfolding, solubility changes and aggregation as well as any alterations in the lens fiber structure itself.  They can be acquired by secondary effects such as UV light exposure, mechanical trauma, poor nutrition, exposure to toxic substances or by contributions by other ophthalmic diseases (such as uveitis or glaucoma). Cataracts are also known to be age related, where they are a normal part of the aging process; or inherited, as a result of a genetic defect. 

ACS are one the most commonly cataract affected dog breeds. The disease may impair the dogs’ vision, which in turn may cause behavior problems. Inherited cataracts in ACS are thought to appear sometime between 2-5 years of age and progress. They have a spectrum of cataract phenotypes differing in location, progression rate, laterality (uni- or bilateral), genetic background and age of onset.  For this reason, a correct assessment of the phenotype and the selection of a good control sample group for study is crucial for the success of this investigation.  

A cataract can be proven to be inherited by the identification of a responsible gene. We believe that by using Genome Wide Association Studies (GWAS), we would be able to pinpoint the localization of such gene. GWAS is a widely used method for scanning the entire genomes of different individuals in search for a common genetic variation associated with a shared trait. The method uses purified DNA from blood of cases and controls that is placed on chips, and scanned for strategically selected genetic variation markers called single nucleotide polymorphisms (SNPs). A higher frequency of certain SNPs in cases vs. controls, means that these variations are associated with the disease, and may serve as the region identifiers in the genome. Identification of new genetic associations would ultimately lead to designing strategies to detect, and prevent the disease, and may provide insights into possible treatments.

                 

 

 
 

Summary of previous work: 

 

While in the ongoing process of collecting sufficient samples to carry out more detailed genomic studies, candidate gene analysis was performed.  We identified a few candidate genes based on a priori data about the association with the same or similar diseases in the dog and other species, as well as the knowledge of the genes biological function. We have screened twenty-four of the most common cataract causing genes by sequencing the exons of these genes, the part of the gene involved in coding for the actual protein, in cases and controls, for associated variants to this disease. Unfortunately, no association was found. These results have been presented in prior Progress Reports. 

 

Table1.             Screened candidate genes for inherited cataracts in the ACS.   

 

 

Candidate genes

HSF4

CRYAB

CRYAA

TMEM114

LIM2

CRYBA1

CRYGS

SIX1

GJA3

CRYBA4

CRYGD

SIX3

GJA8

CRYBB1

CRYGC

SIX4

MIP

CRYBB2

CRYGA

BFSP4

MAF

CRYBB3

PITX3

BIN3

 

 

Because candidate gene screening is an iterative process, and exclusion does not get you closer to the gene of interest when it is an unknown gene, this approach was discontinued after all likely candidate genes were eliminated. We then directed our efforts to GWAS using an Illumina Canine SNP Chip, and GWAS analysis was performed using DNA form prescreened cases and control ACS. We found that there might be an associated chromosome region, since we found a suggestive signal peak in the preliminary GWAS study. Nonetheless, analysis of the population structure led us to conclude that part of the data was not usable. After reevaluating the records/clinical data and phenotypes of the dogs, we concluded that we do not have sufficient information needed for an accurate re-assessment of cases and controls, and thus our suggestive results cannot be taken as reliable. These points are discussed in sections below.

 

Current methods and results: 

Pedigree analysis: 

Family trees: Cyrillic, a pedigree software, was used to draw the family trees for the ACS’s included on the SNP Chip analysis. Pedigree data was managed and analyzed using the program. Plotting the family tree of the cases helped us in identifying common ancestors among the affected dogs, possibly the origin of the cataract allele; as these common founders are not alive and samples are unavailable for DNA analysis, this information, although extremely important, is of limited immediate use.

Pedigree investigation has not revealed a clear mode of inheritance. A likely explanation is that as a phenotype, 'cataract' lacks specificity when applied on a population basis that are inconsistently characterized; as well, the term groups genetic and non-genetic causes, and the former may represent different genetic defects. At present, autosomal recessive, autosomal dominant with incomplete penetrance, and compound heterozygous, are still possible mechanisms. However, as we were able to link most of our affected subjects to three (3) common ancestors, it is likely that autosomal recessive inheritance is at play, and that emphasis should be placed in refining the cataract diagnosis in the descendants. That work is currently in progress. 

Phenotype reassessment: 

Research study forms: As stated in our previous progress report, we put every effort to have Dr. Aguirre examine all the study dogs (thus, counting on a reliable phenotype assessment consistent between samples). Nonetheless, we realized early on that this would be impractical, thus dogs examined by other ACVO diplomates are included in the study. In order to avoid any misinterpretation of the data provided by the examining ophthalmologist, a standardized eye exam form was developed. Although the forms are useful, we have noticed that not every ophthalmologist seems to use them. This has been a problem as the forms used-OFA-CAER-are inadequate for consistent diagnosis.

Samples received: Currently we have 604 participant dogs signed up in our study. We were provided with documentation (veterinary/surgical notes, eye exam forms, genetic testing certificates, etc…) for 547 of the 604 study subjects. However, as stated previously, only about one third of the records are accurate, relevant and up to date.  Additionally, we have collected 563 blood samples and 25 DNA samples, for an overall total of 588.  The DNA samples were isolated from blood or buccal swabs by personnel at OptiGen LLC. All of the blood samples have been sent to us in EDTA lined tubes, to prevent clotting. 

Second analysis of records: We have reassessed the eye exam forms/records, and the dog’s phenotypes in order to improve the power of our analysis. We have contacted the owners of the dogs included in the SNP analysis via e-mail or phone for an update on the dog’s well-being, as well as a recent ophthalmology eye exam form. We found them overall helpful, kind and cooperative. 

Current situation: We had to exclude several of the cases that were used in the SNP Chip analysis due to a halt in cataract progression, a lack of updates on the dog's health and the dog developing other eye problems where we could not be sure if the cataract is secondary to other problems.  

Through record and phenotype reassessment we have discovered that ACS seem to exhibit two distinct phenotypes of what we suspect is inherited cataract formation. Until now we have associated inherited cataracts with an early (ages 2-5) onset bilateral formation. However, through phenotype and pedigree analysis, we have noted that there seems to be a second cataract phenotype, where one eye develops a cataract at an early age and several years later a second cataract appears in the other. At present, we are handling the as different inherited disorders, but will combine them if the research data supports such an approach.

Genomic markers analysis:

GWAS: Genome Wide Association Studies are a statistical analysis based on cases (46) and controls (24) within a population. The aim of such studies is to associate a specific genomic region and its markers to a cohort of study cases. This can be achieved by variation comparison of cases against a similar-sized cohort of controls.  We carried out the GWAS with the GenABEL (R package) software. After the preliminary results, we proceeded to phase out the study cases and controls no longer considered reliable. In order to further improve the analysis we have also considered other options, such as sub-division of cases into groups based on the age of onset, laterality, position of the cataract in the lens and so on. 

The results were inconclusive. We believe that weeding out some of the samples might have lowered the power of the analysis. Comparing all the cases versus all the controls did show a suggestive peak under the significance threshold. However, analysis of quantiles suggested the possibility of more than one allele associated with the cataract in the putative candidate region. Furthermore, we established that the inconclusiveness of the GWAS can be attributed to the following: 

-         The population structure did not allow for a good power for the analysis at the current state. In other words, the dogs in the study seem to be related to each other, at least distantly, thus their genetic proximity, in addition the with the small study population size, could have led to difficulties in distinguish cases and controls in our statistical analysis. 

-         The disease has an incomplete penetrance, hence some of the controls are in fact cases. This is yet to be definitively proven, but we we have to consider this possibility in the analysis.

-         The disease could be multi-genic, so that two different mutations in the genome are needed to lead to the phenotype.

-         The disease could be actually 2 or even 3 different types of cataracts, caused by different mutations in the same gene.

-         The disease could be in fact be a combination of the above.

Please note that in case of lack of power for the experiment a greater number of cases plus a greater and better number of controls are absolutely crucial for a reliable mapping of candidate regions. A greater sampling of cases and controls is crucial in any of the above scenarios (as an example, the subdivision of the cases in sub-groups means the power of the experiment is dramatically lowered and thus the current analysis unreliable until new samples are added). 

 

Phasing: mach1, a phasing software was used to phase the chromosomes of the population, starting with the ones containing suggestive peaks in the GWAS analysis. Our preliminary analysis of the phased chromosomes (the phasing was carried out with a population-based method and used the whole dataset) confirmed that even in the putative candidate regions, the phased haplotypes show more than one allele associated with the cases. We are currently re-running part of the phasing on different parameters in order to validate the phasing and find an optimum for the output. Once the phenotype re-assessment is finished, the analysis will be repeated. An increase in the sample size of genotyped dogs in the study population would help immensely in the phasing.

Homozygosity mapping: SNP marker data has been used to carry out homozygosity mapping on the cases and the controls, in order to find a homozygous region identical by descent (IBD) among the cases and not in the controls. Plink software was used in the mapping. The homozygosity mapping carried out on the preliminary data before the phenotype re-assessment did show six common homozygous regions in the cases not present in the controls. Once the phenotype re-assessment ends, we will repeat the analysis. Note that this preliminary result does not completely exclude the regions since the alleles could be present and diffused in the population, however a very recent causative mutation could be present only in a subgroup of such haplotypes. This has been reported, documented, and demonstrated in animal genetics, and we take this into consideration in the analysis. At the moment, we cannot completely rule a dominant inheritance mechanism with incomplete penetrance. However, as affected dogs have been excluded from the breeding pool, we would have expected a decrease rather than an increase in cataract frequency which has not been the case. Still, the most likely mode of inheritance for the cataracts is autosomal recessive with possible incomplete penetrance.

 

Problems and pitfalls in the current research studies

There were several issues identified in an email to the Board on 4/20/17 which are summarized below with additional comments. 

A-The working hypothesis for this study was that cataracts in ACS were inherited as simple autosomal recessive as described by Yakely and associates in the 1970's (Yakely, Hegreberg et al. , Yakely 1971, Yakely 1978). Those studies were population based with small sample sizes, so they lacked the rigor of prospective breeding studies of dogs of known phenotypes, but were useful as they provided a sufficient basis for establish the heritability of cataracts in the breed. However, our research now finds that the disease is more complicated. While it is likely to be autosomal recessive, not all dogs fit this mode of inheritance. Similarly, not all dogs affected with cataracts may have the inherited form. As many of the examinations received are far from adequate with incomplete or few details, many of the samples/examinations are of limited value at this early stage of the research. At later stages of the research most will be quite helpful. Lastly, we are finding several affected dogs that have cataracts in only one eye, and the fellow eye develops the cataract later if at all. We suspect that these too are inherited, but don’t know if they represent a different manifestation of the same disease or a different genetic defect. Only when we find the gene for one form of cataract, will we know about the others. This new appreciation for cataracts in the breed has come from examining >200+ dogs over a 2.5 year period, and reviewing ~550 records from both normal and affected dogs that have been enrolled in the study. 

 

B-We have received 588samples and examination records from dogs for the study. Of these, 375 were excluded, for various reasons, from the initial analysis. The balance, 213 dogs, used in the analysis can be divided into:

         Controls: 68

                   Too young at present for study inclusion: 20

                  Inadequate follow up data provided as requested: 12

                   Insufficient data in medical record for inclusion: 2

                   "Gold standard" control (ages 10 and up): 34 

To be certain of our normal control population, we want old dogs with no cataracts. For example, if a dog we considered normal at 8 years now develops cataracts that look like the inherited at a later time point, we move him/her from the 'certain normal' to the 'likely normal' category. These moves in category reduce the number of samples that can be considered for analysis, and thus reduce the power and likelihood of finding the genomic region(s) that has (have) the gene(s) of interest.

          Affected: 145

                  Insufficient data in medical record for inclusion: 32

                  Inadequate follow up data provided as requested: 65

                  Dogs too young/too old at this stage of the cataract study: 15

"Gold standard" affected (ages 2-5); these includes dogs with bilateral cataracts (n=20) and dogs with unilateral cataracts that subsequently involved both eyes (n=13):  33

The category "Inadequate follow up data provided as requested" is critical to ascertain the potential heritability of a cataract. For example, if a cocker <5 yrs is found to have cataracts that meet our strict definition of 'likely inherited', we need to have follow up information that these cataracts progress. If they do not, the samples go into the “less likely” category in the analysis.

C-Difficulty with obtaining follow up information on control and affected dogs. In an effort to refine the GWAS analysis, we contacted several owners to obtain this information. Initially, although we received this needed information on just over 60% of the requests, only 6 of 28 have helped move the study forward For the balance, we are waiting, and the club has been extremely helpful and pro-active in facilitation getting the additional details. Still, problems do occur as, e.g. some owners will go eye clinics where a substandard examination will be done, or where the incorrect forms are used, so the follow up information will not be what we need. Others will go to a vet, not an ophthalmologist, so that too will be inadequate. And lastly, many will not go for the update examination. 

 

Future prospects:

In regard to the SNP chip data analysis, the next steps are tightly tied with the phenotype re-assessment. In fact, only after the whole documentation update (possible with the full collaboration of the breeders and with a complete and informative filling of the forms) we can proceed toward a better in-depth analysis of our cases and controls. This hopefully will improve the quality of the overall analysis, and of any analysis of sub-populations of cases (laterality, age of onset, or any other parameter selected). A greater cohort of controls (up to twice the number of cases) has been demonstrated as vital to obtain good power in GWAS analyses.  

Furthermore, a greater number of cases and controls will be needed to map the regions of the genome associated with cataract in case the inheritance mechanism is more complex than a simple autosomal recessive one. This would be particularly crucial in case of a multigenic loci (more power possibly needed), or in case we are indeed facing more than one cataract type in the same cohort. A careful subdivision of the cases in sub-populations needs an overall greater number of cases genotyped in order to have results above the significance threshold for each of the sub-populations. In the same way, a greater cohort of both cases and controls would make phasing more reliable. The results from such analysis would reveal (after a detailed case-control comparison) data that could be integrated with GWAS and homozygosity without excluding any possibility, such as the presence of causative variants in the form of a compound heterozygous. For this reason, we present the possibility that new group of dogs must be genotyped. To this end, a re-examination of all the research records along with additional submissions have identified 19 additional cases and 34 controls, and these are presently being submitted for SNPchip  genotyping. 

In order to ensure the best quality of work, and to gain reliable results, every sample/record sent to us does/will undergo a rigorous examination and selection procedure. Strict requirements are a must for any genetic analysis, and to ensure any progress.  Dogs that have additional ophthalmic problems or no cataract progression will be excluded from our study population, since the cataract might be secondary.  

We cannot stress enough to study participants how important it is to keep us updated about any changes to the dog’s well-being. In the case of affected dogs that have been submitted in the study, we need to build up a timeline and closely follow their health status to see if there is any progression in the cataract, and to properly assess if the opacity is due to inheritance. Dogs considered to be “clear” also need to be closely monitored, to see if indeed they can be considered as such. In order to avoid any misjudgment of the dog’s condition the standardized eye exam form needs to be fully completed by the veterinary ophthalmologist. We also ask study participants to let us know if the dog has died, and to provide the last available eye examination form.  Also, the dog’s current owner address/phone number/e-mail should be up to date in order for our team to contact if new information is required. Such updates don’t only save us time, but precious resources, and thus ultimately money.  

We are still recruiting ACS for our study, and collecting eye exam records/blood samples. We are mostly interested in dogs that have developed cataracts (bilateral or unilateral) at an early age, and dogs that had no cataracts appearing up till the age of 10 and older. We feel that dogs at 10 years of age with no cataract formation would make a perfect control for our study. Currently we are in the need of at least 24-48 more samples from such dogs, in order to get a reliable background to which we can compare affected cockers. 

In the next few months we would like to further assess and confirm the status of the dogs already included in our genome scan data, as well as identify additional cases and controls that can be included in genome wide association studies. 

We thank the owners, breeders and the American Spaniel Club for the continuous support throughout our study. Our search for the ACS cataract gene/mutation would not be possible without their much appreciated dedication and help. We hope to continue this positive relationship in future research.

  Progress Report:                                                       May 31, 2017 

 

  

Molecular Genetic Studies of Inherited Cataracts in the American Cocker Spaniel  

Personnel: 

University of Pennsylvania 

Gustavo Aguirre, VMD, PhD; Principal Investigator 

Leonardo Murgiano, PhD; Post-doctoral fellow and Project Scientist 

(Doreen Becker, DVM, PhD; Post-doctoral fellow and former Project Scientist)

Jessica Niggel, M.Sc., Research scientist 

OptiGen, LLC 

Susan Pearce-Kelling, BS, MS; Research manager 

Aušra Milano, PhD; Research scientist

 

Objectives: 

Cataracts are the most common cause of vison impairment in humans and are often observed in animal models such as mice, sheep, cattle and swine. They are also one of the most frequent ophthalmic diseases, as well as a major cause of blindness in dogs, affecting both mixed and pure breeds. The American Cocker Spaniel (ACS) breed is one of the most frequently affected. According to the ACVO “Blue Book” (2014 edition), ACS cataract prevalence ranges from 8.77% to 11%. However, this number includes both acquired and inherited cataracts, where the latter category contains cataract phenotypes that are clinically similar, but may have a different genetic etiology and only a superficial clinical similarity. ACS dogs with inherited cataracts are born with normal lenses, which then proceed to opacify over time, leading to blindness by 2-10 years of age. The mode of inheritance in ACS has been proposed to be autosomal recessive and there are no gene-based tests available. Our project focuses on the identification of gene(s) causing the most common form of cataract in ACS and on validating its inheritance mechanism. Once the gene and mutation is recognized, ‘atypical cases’ will be included in further analyses. 

 

Background: 

Cataracts are often an inherited condition, characterized as any opacity/cloudiness of the lens, which may impair vision or cause blindness. The opacities may vary in size, shape, localization, age of onset, progression rate and cause. They usually arise due to lens protein misfolding, solubility changes and aggregation as well as any alterations in the lens fiber structure itself.  They can be acquired by secondary effects such as UV light exposure, mechanical trauma, poor nutrition, exposure to toxic substances or by contributions by other ophthalmic diseases (such as uveitis or glaucoma). Cataracts are also known to be age related, where they are a normal part of the aging process; or inherited, as a result of a genetic defect. 

ACS are one the most commonly cataract affected dog breeds. The disease may impair the dogs’ vision, which in turn may cause behavior problems. Inherited cataracts in ACS are thought to appear sometime between 2-5 years of age and progress. They have a spectrum of cataract phenotypes differing in location, progression rate, laterality (uni- or bilateral), genetic background and age of onset.  For this reason, a correct assessment of the phenotype and the selection of a good control sample group for study is crucial for the success of this investigation.  

A cataract can be proven to be inherited by the identification of a responsible gene. We believe that by using Genome Wide Association Studies (GWAS), we would be able to pinpoint the localization of such gene. GWAS is a widely used method for scanning the entire genomes of different individuals in search for a common genetic variation associated with a shared trait. The method uses purified DNA from blood of cases and controls that is placed on chips, and scanned for strategically selected genetic variation markers called single nucleotide polymorphisms (SNPs). A higher frequency of certain SNPs in cases vs. controls, means that these variations are associated with the disease, and may serve as the region identifiers in the genome. Identification of new genetic associations would ultimately lead to designing strategies to detect, and prevent the disease, and may provide insights into possible treatments.

                 

 

 
 

Summary of previous work: 

 

While in the ongoing process of collecting sufficient samples to carry out more detailed genomic studies, candidate gene analysis was performed.  We identified a few candidate genes based on a priori data about the association with the same or similar diseases in the dog and other species, as well as the knowledge of the genes biological function. We have screened twenty-four of the most common cataract causing genes by sequencing the exons of these genes, the part of the gene involved in coding for the actual protein, in cases and controls, for associated variants to this disease. Unfortunately, no association was found. These results have been presented in prior Progress Reports. 

 

Table1.             Screened candidate genes for inherited cataracts in the ACS.   

 

 

Candidate genes

HSF4

CRYAB

CRYAA

TMEM114

LIM2

CRYBA1

CRYGS

SIX1

GJA3

CRYBA4

CRYGD

SIX3

GJA8

CRYBB1

CRYGC

SIX4

MIP

CRYBB2

CRYGA

BFSP4

MAF

CRYBB3

PITX3

BIN3

 

 

Because candidate gene screening is an iterative process, and exclusion does not get you closer to the gene of interest when it is an unknown gene, this approach was discontinued after all likely candidate genes were eliminated. We then directed our efforts to GWAS using an Illumina Canine SNP Chip, and GWAS analysis was performed using DNA form prescreened cases and control ACS. We found that there might be an associated chromosome region, since we found a suggestive signal peak in the preliminary GWAS study. Nonetheless, analysis of the population structure led us to conclude that part of the data was not usable. After reevaluating the records/clinical data and phenotypes of the dogs, we concluded that we do not have sufficient information needed for an accurate re-assessment of cases and controls, and thus our suggestive results cannot be taken as reliable. These points are discussed in sections below.

 

Current methods and results: 

Pedigree analysis: 

Family trees: Cyrillic, a pedigree software, was used to draw the family trees for the ACS’s included on the SNP Chip analysis. Pedigree data was managed and analyzed using the program. Plotting the family tree of the cases helped us in identifying common ancestors among the affected dogs, possibly the origin of the cataract allele; as these common founders are not alive and samples are unavailable for DNA analysis, this information, although extremely important, is of limited immediate use.

Pedigree investigation has not revealed a clear mode of inheritance. A likely explanation is that as a phenotype, 'cataract' lacks specificity when applied on a population basis that are inconsistently characterized; as well, the term groups genetic and non-genetic causes, and the former may represent different genetic defects. At present, autosomal recessive, autosomal dominant with incomplete penetrance, and compound heterozygous, are still possible mechanisms. However, as we were able to link most of our affected subjects to three (3) common ancestors, it is likely that autosomal recessive inheritance is at play, and that emphasis should be placed in refining the cataract diagnosis in the descendants. That work is currently in progress. 

Phenotype reassessment: 

Research study forms: As stated in our previous progress report, we put every effort to have Dr. Aguirre examine all the study dogs (thus, counting on a reliable phenotype assessment consistent between samples). Nonetheless, we realized early on that this would be impractical, thus dogs examined by other ACVO diplomates are included in the study. In order to avoid any misinterpretation of the data provided by the examining ophthalmologist, a standardized eye exam form was developed. Although the forms are useful, we have noticed that not every ophthalmologist seems to use them. This has been a problem as the forms used-OFA-CAER-are inadequate for consistent diagnosis.

Samples received: Currently we have 604 participant dogs signed up in our study. We were provided with documentation (veterinary/surgical notes, eye exam forms, genetic testing certificates, etc…) for 547 of the 604 study subjects. However, as stated previously, only about one third of the records are accurate, relevant and up to date.  Additionally, we have collected 563 blood samples and 25 DNA samples, for an overall total of 588.  The DNA samples were isolated from blood or buccal swabs by personnel at OptiGen LLC. All of the blood samples have been sent to us in EDTA lined tubes, to prevent clotting. 

Second analysis of records: We have reassessed the eye exam forms/records, and the dog’s phenotypes in order to improve the power of our analysis. We have contacted the owners of the dogs included in the SNP analysis via e-mail or phone for an update on the dog’s well-being, as well as a recent ophthalmology eye exam form. We found them overall helpful, kind and cooperative. 

Current situation: We had to exclude several of the cases that were used in the SNP Chip analysis due to a halt in cataract progression, a lack of updates on the dog's health and the dog developing other eye problems where we could not be sure if the cataract is secondary to other problems.  

Through record and phenotype reassessment we have discovered that ACS seem to exhibit two distinct phenotypes of what we suspect is inherited cataract formation. Until now we have associated inherited cataracts with an early (ages 2-5) onset bilateral formation. However, through phenotype and pedigree analysis, we have noted that there seems to be a second cataract phenotype, where one eye develops a cataract at an early age and several years later a second cataract appears in the other. At present, we are handling the as different inherited disorders, but will combine them if the research data supports such an approach.

Genomic markers analysis:

GWAS: Genome Wide Association Studies are a statistical analysis based on cases (46) and controls (24) within a population. The aim of such studies is to associate a specific genomic region and its markers to a cohort of study cases. This can be achieved by variation comparison of cases against a similar-sized cohort of controls.  We carried out the GWAS with the GenABEL (R package) software. After the preliminary results, we proceeded to phase out the study cases and controls no longer considered reliable. In order to further improve the analysis we have also considered other options, such as sub-division of cases into groups based on the age of onset, laterality, position of the cataract in the lens and so on. 

The results were inconclusive. We believe that weeding out some of the samples might have lowered the power of the analysis. Comparing all the cases versus all the controls did show a suggestive peak under the significance threshold. However, analysis of quantiles suggested the possibility of more than one allele associated with the cataract in the putative candidate region. Furthermore, we established that the inconclusiveness of the GWAS can be attributed to the following: 

-         The population structure did not allow for a good power for the analysis at the current state. In other words, the dogs in the study seem to be related to each other, at least distantly, thus their genetic proximity, in addition the with the small study population size, could have led to difficulties in distinguish cases and controls in our statistical analysis. 

-         The disease has an incomplete penetrance, hence some of the controls are in fact cases. This is yet to be definitively proven, but we we have to consider this possibility in the analysis.

-         The disease could be multi-genic, so that two different mutations in the genome are needed to lead to the phenotype.

-         The disease could be actually 2 or even 3 different types of cataracts, caused by different mutations in the same gene.

-         The disease could be in fact be a combination of the above.

Please note that in case of lack of power for the experiment a greater number of cases plus a greater and better number of controls are absolutely crucial for a reliable mapping of candidate regions. A greater sampling of cases and controls is crucial in any of the above scenarios (as an example, the subdivision of the cases in sub-groups means the power of the experiment is dramatically lowered and thus the current analysis unreliable until new samples are added). 

 

Phasing: mach1, a phasing software was used to phase the chromosomes of the population, starting with the ones containing suggestive peaks in the GWAS analysis. Our preliminary analysis of the phased chromosomes (the phasing was carried out with a population-based method and used the whole dataset) confirmed that even in the putative candidate regions, the phased haplotypes show more than one allele associated with the cases. We are currently re-running part of the phasing on different parameters in order to validate the phasing and find an optimum for the output. Once the phenotype re-assessment is finished, the analysis will be repeated. An increase in the sample size of genotyped dogs in the study population would help immensely in the phasing.

Homozygosity mapping: SNP marker data has been used to carry out homozygosity mapping on the cases and the controls, in order to find a homozygous region identical by descent (IBD) among the cases and not in the controls. Plink software was used in the mapping. The homozygosity mapping carried out on the preliminary data before the phenotype re-assessment did show six common homozygous regions in the cases not present in the controls. Once the phenotype re-assessment ends, we will repeat the analysis. Note that this preliminary result does not completely exclude the regions since the alleles could be present and diffused in the population, however a very recent causative mutation could be present only in a subgroup of such haplotypes. This has been reported, documented, and demonstrated in animal genetics, and we take this into consideration in the analysis. At the moment, we cannot completely rule a dominant inheritance mechanism with incomplete penetrance. However, as affected dogs have been excluded from the breeding pool, we would have expected a decrease rather than an increase in cataract frequency which has not been the case. Still, the most likely mode of inheritance for the cataracts is autosomal recessive with possible incomplete penetrance.

 

Problems and pitfalls in the current research studies

There were several issues identified in an email to the Board on 4/20/17 which are summarized below with additional comments. 

A-The working hypothesis for this study was that cataracts in ACS were inherited as simple autosomal recessive as described by Yakely and associates in the 1970's (Yakely, Hegreberg et al. , Yakely 1971, Yakely 1978). Those studies were population based with small sample sizes, so they lacked the rigor of prospective breeding studies of dogs of known phenotypes, but were useful as they provided a sufficient basis for establish the heritability of cataracts in the breed. However, our research now finds that the disease is more complicated. While it is likely to be autosomal recessive, not all dogs fit this mode of inheritance. Similarly, not all dogs affected with cataracts may have the inherited form. As many of the examinations received are far from adequate with incomplete or few details, many of the samples/examinations are of limited value at this early stage of the research. At later stages of the research most will be quite helpful. Lastly, we are finding several affected dogs that have cataracts in only one eye, and the fellow eye develops the cataract later if at all. We suspect that these too are inherited, but don’t know if they represent a different manifestation of the same disease or a different genetic defect. Only when we find the gene for one form of cataract, will we know about the others. This new appreciation for cataracts in the breed has come from examining >200+ dogs over a 2.5 year period, and reviewing ~550 records from both normal and affected dogs that have been enrolled in the study. 

 

B-We have received 588samples and examination records from dogs for the study. Of these, 375 were excluded, for various reasons, from the initial analysis. The balance, 213 dogs, used in the analysis can be divided into:

         Controls: 68

                   Too young at present for study inclusion: 20

                  Inadequate follow up data provided as requested: 12

                   Insufficient data in medical record for inclusion: 2

                   "Gold standard" control (ages 10 and up): 34 

To be certain of our normal control population, we want old dogs with no cataracts. For example, if a dog we considered normal at 8 years now develops cataracts that look like the inherited at a later time point, we move him/her from the 'certain normal' to the 'likely normal' category. These moves in category reduce the number of samples that can be considered for analysis, and thus reduce the power and likelihood of finding the genomic region(s) that has (have) the gene(s) of interest.

          Affected: 145

                  Insufficient data in medical record for inclusion: 32

                  Inadequate follow up data provided as requested: 65

                  Dogs too young/too old at this stage of the cataract study: 15

"Gold standard" affected (ages 2-5); these includes dogs with bilateral cataracts (n=20) and dogs with unilateral cataracts that subsequently involved both eyes (n=13):  33

The category "Inadequate follow up data provided as requested" is critical to ascertain the potential heritability of a cataract. For example, if a cocker <5 yrs is found to have cataracts that meet our strict definition of 'likely inherited', we need to have follow up information that these cataracts progress. If they do not, the samples go into the “less likely” category in the analysis.

C-Difficulty with obtaining follow up information on control and affected dogs. In an effort to refine the GWAS analysis, we contacted several owners to obtain this information. Initially, although we received this needed information on just over 60% of the requests, only 6 of 28 have helped move the study forward For the balance, we are waiting, and the club has been extremely helpful and pro-active in facilitation getting the additional details. Still, problems do occur as, e.g. some owners will go eye clinics where a substandard examination will be done, or where the incorrect forms are used, so the follow up information will not be what we need. Others will go to a vet, not an ophthalmologist, so that too will be inadequate. And lastly, many will not go for the update examination. 

 

Future prospects:

In regard to the SNP chip data analysis, the next steps are tightly tied with the phenotype re-assessment. In fact, only after the whole documentation update (possible with the full collaboration of the breeders and with a complete and informative filling of the forms) we can proceed toward a better in-depth analysis of our cases and controls. This hopefully will improve the quality of the overall analysis, and of any analysis of sub-populations of cases (laterality, age of onset, or any other parameter selected). A greater cohort of controls (up to twice the number of cases) has been demonstrated as vital to obtain good power in GWAS analyses.  

Furthermore, a greater number of cases and controls will be needed to map the regions of the genome associated with cataract in case the inheritance mechanism is more complex than a simple autosomal recessive one. This would be particularly crucial in case of a multigenic loci (more power possibly needed), or in case we are indeed facing more than one cataract type in the same cohort. A careful subdivision of the cases in sub-populations needs an overall greater number of cases genotyped in order to have results above the significance threshold for each of the sub-populations. In the same way, a greater cohort of both cases and controls would make phasing more reliable. The results from such analysis would reveal (after a detailed case-control comparison) data that could be integrated with GWAS and homozygosity without excluding any possibility, such as the presence of causative variants in the form of a compound heterozygous. For this reason, we present the possibility that new group of dogs must be genotyped. To this end, a re-examination of all the research records along with additional submissions have identified 19 additional cases and 34 controls, and these are presently being submitted for SNPchip  genotyping. 

In order to ensure the best quality of work, and to gain reliable results, every sample/record sent to us does/will undergo a rigorous examination and selection procedure. Strict requirements are a must for any genetic analysis, and to ensure any progress.  Dogs that have additional ophthalmic problems or no cataract progression will be excluded from our study population, since the cataract might be secondary.  

We cannot stress enough to study participants how important it is to keep us updated about any changes to the dog’s well-being. In the case of affected dogs that have been submitted in the study, we need to build up a timeline and closely follow their health status to see if there is any progression in the cataract, and to properly assess if the opacity is due to inheritance. Dogs considered to be “clear” also need to be closely monitored, to see if indeed they can be considered as such. In order to avoid any misjudgment of the dog’s condition the standardized eye exam form needs to be fully completed by the veterinary ophthalmologist. We also ask study participants to let us know if the dog has died, and to provide the last available eye examination form.  Also, the dog’s current owner address/phone number/e-mail should be up to date in order for our team to contact if new information is required. Such updates don’t only save us time, but precious resources, and thus ultimately money.  

We are still recruiting ACS for our study, and collecting eye exam records/blood samples. We are mostly interested in dogs that have developed cataracts (bilateral or unilateral) at an early age, and dogs that had no cataracts appearing up till the age of 10 and older. We feel that dogs at 10 years of age with no cataract formation would make a perfect control for our study. Currently we are in the need of at least 24-48 more samples from such dogs, in order to get a reliable background to which we can compare affected cockers. 

In the next few months we would like to further assess and confirm the status of the dogs already included in our genome scan data, as well as identify additional cases and controls that can be included in genome wide association studies. 

We thank the owners, breeders and the American Spaniel Club for the continuous support throughout our study. Our search for the ACS cataract gene/mutation would not be possible without their much appreciated dedication and help. We hope to continue this positive relationship in future research. 

 

We Can Not Stop Now!

We are into the third year of the Dr. Aguirre led University of Pennsylvania study on finding a

marker for inherited cataracts in cocker spaniels. Dr. Aguirre and his University of Pennsylvania

team are analyzing all the samples gathered to date to eventually select samples for further

genome sequence analysis. Out of close to 550 samples gathered thus far for the University,

24 normal dogs and 24 affected dogs have been selected and there are also another 20 afflicted

dogs that are on standby for further research as well. It is hoped that additional volunteer

DNA and eye exams will yield additional subject genetics to be included in the study.

The bottom line - the need for new DNA submissions and eye exams continues unabated. If

you have not participated in the study – or have new dogs to include – please do so. Dr. Aguirre

and the team are also requesting that reexamination results of existing submissions is critical.

Specifically for the study Dr. Aguirre is requesting:

o New submissions of affected dogs with cataracts developing between 2-4 years

o Follow up examinations on dogs previously submitted that had suspected inherited

cataract in one eye. The research team wants to see if it’s developing in the other

eye or if there is any change in the original cataract. This is IMPROTANT information

to have and not enough people are sending in follow on information on affected

dogs. It’s NEEDED!!!!!

o Non affected dogs older than 8 years

o Please use these forms http://www.optigen.com/doc/9_30_15_Cocker_Cataract.pdf

o Since it is assumed the majority of cockers outside the US come from US bred stock,

it would be great if our foreign fancy would also participate in the study. Dr. Aguirre

would welcome these as well for the study but the eye exams MUST use the forms

indicated here and the exams MUST be done by an ophthalmologist that is an ECVO

certified diplomat (European College of Veterinary Ophthalmologists) or they will

not be useful.

With over 500 submissions thus far, you may be thinking when will we have enough dogs for

the study? The simple answer is we will have enough samples for the study when we finally

find the gene marker for cataracts in Cockers. Until then, this is like searching for a needle in a

haystack. Until we find the cataract gene we need more samples of clear dogs and affected

dogs as well as follow-on samples to the affected dogs you have already provided.

What you might not appreciate is this is not a study in a controlled laboratory environment

where the study subjects are always available in the laboratory. Just as an example, some past

University canine cataract genetic research was in a controlled laboratory study with controlled

breeding, feeding, care and constant examinations by the same veterinarian researchers for

detailed observation of cataract growth and movement. In controlled laboratory studies

afflicted and not afflicted dogs can be examined on a regular basis by the researching set of

veterinarians giving a very detailed observation of the cataract growth and movement.

For the ASC Foundation study with the University we need cockers from the broader general

population way beyond that of a smaller controlled laboratory environment. Due to this the

research team has to rely on the reporting of many different ophthalmologists with differing

skill and reporting expertise. In addition, the University team gets one report on an affected

dog – or perhaps one per year if at all – when they would like to see them regularly in an ideal

situation. This is why it is especially important to use Dr. Aguirre’s University of PA study forms

with your ophthalmologist. These forms ask for the detail Dr. Aguirre and the research team

would normally ask for and examine in controlled environments. Use of these forms are the

next best thing to the University and Dr. Aguirre doing all the cataract tests themselves. Since

that is not feasible thus the forms. And our urging that they must be used by your examining

ophthalmologist. http://www.optigen.com/doc/9_30_15_Cocker_Cataract.pdf

In July we will receive from Dr. Aguirre the mid-year research report which we will share with

you as soon as available. But we cannot stop gathering eye exams and DNA samples. Please

arrange with your local ophthalmologists for those continuing examinations as well. Thank you

all for your funding and participation in the study. But, until we find the genetic marker, we

must continue forward.

Jamie Hubbard and Karin Linde Klerholm generously donated the fees they received for judging the Capitol City Cocker Spaniel Club specialties to "Eye Support Cockers", the ASC Foundation's fundraising initiative to support Dr. Gustavo Aguirre's molecular genetic cataract study being conducted at the University of Pennsylvania. Many thanks to Jamie and Karin for their wonderful support of this critical project, and to Cathy Carey for taking this great photo. As you know, Dr. Aguirre and his team are also in need of more Cockers for inclusion in the study. To help meet this need, ASCF is offering a FREE BLOOD DRAW at the National in St. Louis. Please see the below information and consider taking advantage of this opportunity!

Let’s Make a clear future for Cockers at the ASC National this July!!! Calling all Cockers with pedigrees! WHAT: FREE blood draw for the ASC Foundation-funded genetic cataract study being conducted by Dr. Gustavo Aguirre at the University of Pennsylvania ***THIS DRAW, INCLUDING SHIPPING, WILL BE FREE ***SHOW COATS WILL NOT BE AFFECTED WHERE: ASC Summer National – Purina Farms, tack room area WHEN: Thursday, July 21, 2 – 5 P.M. Friday, July 22, 1 – 6 P.M. WHAT YOU NEED TO BRING:

*Any Cocker with a pedigree – affected and unaffected - show, performance, pet – dogs DO NOT have to be entered in the show *A pedigree for each Cocker to be drawn *ALL paperwork from recent and previous eye exams for those dogs – INCLUDING the completed research form found on the Optigen site: http://www.optigen.com/doc/9_30_15_Cocker_Cataract.pdf *If your dog(s) have not been examined recently, you can have that done AFTER the show and then mail the completed paperwork (including the University of Pennsylvania research form) directly to Optigen. For information, please contact: Elena Duggan, cliffsiders@hotmail.com 914 805 3394

 

  • Dr Aguirre Research Update - Read Here
  • Watch Dr. Aguirre's presentation at the 2015 ASC National
  • Get your forms for the Cataract Research here
  • Donate Now the EASY way.  Shop at Amazon Smile and pick ASCF as your charitable organization.  For more info go to https://smile.amazon.com/about
  • On behalf of the Board of Directors of the American Spaniel Club Foundation (Foundation) we arepleased to announce the contract between the Foundation and the University of Pennsylvania for the Molecular Genetic Studies of Inherited Cataracts in the Cocker Spaniel has been signed.The purpose of this grant is to conduct research for a genetic test for cataracts for Cocker Spaniels that can be made available to breeders to improve the quality of their breeding programs by identifying genetically normal, affected and carrier dogs.    As part of this agreement, the Foundation agrees to reimburse the University for at least $150,000 for this grant paid over the 3 year period of the grant.   

 

Donatations to date for the Cararact Research Project

To make a donation to the University Of Pennsylvania/ Dr. Aguirre cataract research project, "Eye Support Cockers", via personal check, please send to:

Laurie Foley
6627 Robin Road
Dallas Tx 75209

BE SURE TO PUT IN THE MEMO LINE:  Dr. Aguirre cataract project

 

$6000 and over (in order of highest amount donated)

  • Stephanie Kaul
  • American Spaniel Club Foundation
  • Calvin and Dale Ward

$3000 to $5999 (in alphabetical order)

  • Nan Faith Arnold and Linda L. Wiland
  • Regina and Richard Beinhauer
  • Jan Bruce- Winelight
  • James Davis - EPIC
  • Carolee Douglas
  • Elena and Stephen Duggan
  • Laurie Ferland - Somerset Cockers
  • Linda G. Moore and Laurie Foley
  • Kyle and David Richey and Tracy Lynn Carroll
  • Jim and Kathy Van Elswyk - Foxhill
  • Jane and Beth Williams – JanBet Cockers

$1000 to $2999 (in alphabetical order)

  • Charles Born and Kevin Dincher
  • Brenda J. McManigle -- Abbey Lane Cocker
  • Kathleen Patterson – Show Me Spaniels
  • Anonymous

Up to $1000 (in alphabetical order)

  • ACN Review (Kelly Ladoucer)
  • Laurie Acklin
  • Animal Hospital of Monticello - Monticello, IL
  • Lindy Bennet -- Toybox Cockers
  • Joyce Berthal
  • Lindy Beeson
  • Christine Brock
  • Ruth Corsaw
  • Jackie Curry
  • Patty Darke
  • Angelina Dobmeier
  • David and Linda Donaldson
  • Carol Edwards
  • Connie Edwards
  • Patricia Elkins
  • Sharon Elliott
  • Bob Ennis
  • Kenyon Fairey
  • James and Debbie Fehring – Shaman Cockers
  • Sherry Forslund
  • Motoei Furukawa
  • Csaba A. Havasi – Madmans Cometh
  • Laura Heidrich
  • Joyce E. Henderson
  • Dianne Hill and Elphie
  • Jamie Hubbard
  • Michael Kaufman
  • Colleen Keough
  • Judith Wick Klepp – Jaywyck Cockers 
  • Karin Linda Klerholm
  • Donna and John Kornmeyer
  • Deborah Knight 
  • Donna and John Kornmeyer
  • Kelly Ladouceur and Farley
  • Linda Lareau
  • Gabriella Ledeczi 
  • Doug and Marleta McFarlane
  • Friends and Family of Moonglow Gardens Cockers 
  • Mary and Carl Napper
  • Lynn Nelson 
  • Marlene Ness
  • Sam and Wilma Parker
  • Performance Pets
  • Wilma and Sam Parker 
  • Kathy Patterson and the Show Me Spaniels 
  • Bonnie and Wilson Pike
  • Linda and Mike Pitts
  • Savannah Pitts
  • Mark Ragusa
  • Per Ingar Rismyhr
  • Debra Rudman
  • Quinn Ruvacava 
  • Judith Sarkisian
  • Dan Sena
  • Clyde and Barbara Shaw
  • Jackie and Terry Stacy
  • Mark Taylor
  • Julie Virosteck
  • Jack and Neville Ward
  • Sandie Weber
  • Bruce VanDeman
  • Adam Wierbianski
  • Darin Yamaski
  • Anonymous

In Honor of In Memory Of

  • In honor of Stephanie Kaul:  Jackie Curry, Michaela Garloff
  • In honor of Elena Duggan:  Matthew Duggan and Kimberly O'Donnell
  • In honor of Pistal: Debra Rudman
  • In honor of Marlene Ness and Mark Ragusa:  Brent Wetnicka
  • In honor of Linda G. Moore – Lucille Foley
  • In honor of Linda Lareau: Michaela Garloff
  • In honor of Tracy Lynn and Ken Carroll and the Top Dog Inn: Stephanie Kaul
  • In honor of Stella Rowlett: Stephanie Kaul
  • In honor of all the dogs I’ve ever owned or bred: Stephanie Kaul
  • In honor of Kerri Leeman and Tanya Bruce: Jackie Horton, wedding guests, Suncoast Cocker Spaniel Club
  • In honor of Kevin Hughes excellent job with the Specialty show: Ohio Valley Cocker Spaniel Club
  • In memory of Bertha Roister O’Connell, Kathleen Patterson’s mother:  Elena Duggan
  • In memory of Ken Feller:  Elena Duggan
  • In memory of Farley, aka WCD: Michaela Garloff, Debra Rudman
  • In memory of Harlow – Dee Torgerson-Rismyer
  • In memory of Charles W. Self: Jane and Beth Williams, Kathleen Patterson
  • In memory of Steve Virosteck: Kathleen Patterson
  • In memory of Ruth Bumgartner: Sam and Wilma Parker
  • In memory of CH Jawat’s Golden Girl, ROM:  Kathy Patterson and the Show Me Spaniels
  • In memory of Donna Wirth:  Colleen Keough
  • In memory of Darcy: Lynn Nelson
  • In memory of Joe Hannah – SANS MAX:  Kathy Reid, Carol Pilcher, Dena Pilcher Vincent, and Margaret Hawvermale
  • In memory of Julez Blue Diamond:  Quinn Ruvacava
  • In memory of Ken Williams and AYCE:  Regina Beinhauer,Cocker Spaniel Specialty Club of Georgia, Elena Duggan, Bob Ennis, Billy Gorodner,Harriett Kamps, Colleen Keough and Randy Lake, Diane Kepley, Debbie Knight, Karen Knight, Linda G.Moore and Laurie Foley, Sam and Wilma Parker, Kathy Patterson, Susan Roman, Kate Romanski, Marilyn Spacht, The Cocker Spaniel Club of Southeast FL
  • In memory of Dorothy Mustard, Must Do Cockers:  Jane and Beth Williams
  • In memory of Jim Yates, Storybook Cockers:  Jane and Beth Williams
  • In memory of Joy Chesser, Joy's Cockers:  Deborah Y. Verdon, Debutante Cockers and Cindy Sacony
     
  • American Cocker Spaniel Club of Canada - Ontario Chapter
  • American Cocker Spaniel Club of VIctoria, Australia
  • American Cocker Spaniel Club of Central Ontario
  • Bay Cities Cocker Spaniel Club,
  • Capital City Cocker Club
  • Carolina Piedmont Agility Club – Carolinas Championship Challenge
  • Cocker Spaniel Club of Central Oklahoma
  • Cocker Spaniel Club of Greater New Orleans
  • Cocker Spaniel Club of New Jersey
  • Cocker Spaniel Club of Rhode Island
  • Cocker Spaniel Club of Southeast Florida
  • Cocker Spaniel Club of Tulsa
  • Cocker Spaniel Specialty Club of Dallas
  • Cocker Spaniel Specialty Club of Georgia
  • Connecticut Westchester Cocker Spaniel Club
  • Maryland Cocker Spaniel Club
  • Mid Michigan Cocker Spaniel Club
  • Mission Valley Cocker Spaniel Club,
  • Ohio Valley Cocker Spaniel Club
  • South Atlantic Cocker Spaniel Club
  • Washington State Cocker Spaniel Club
  • West Coast Cocker Spaniel Club

EYE SUPPORT COCKERS EVENTS

CT Westchester Cocker Spaniel Club on-line auction / Marlene Ness ($7,543)

Special thanks to Judith Webb
Auction Item Donors: ACN Review; Will Alexander; Lisa Arnett; Barbara Brickett; Ben Butler; Bettie Campbell;  Helene Chausse; Vickie Clendin; Jackie CurryRuth Dehmel; Stacy Dobmeier; Patricia Elkins; Gay Ernst; Olga Evelyn; Lisa  Gaertner; Jeffrey Hanlin; Charlotte Hansen; Edson Ideriba; Carolyn Kelley; Kelly Ladouceur; Holly Lawson; Jessica Legath; Sue Machem @ Sue’s Snoods; Rhonda Mink; Nana B’s Boutique; Maureen Paskin; Kathy Patterson; Debby  Paz; Pet Portraits by Miranda; Bonnie & Wilson Pike; DiAnn Prock; Mark Ragusa; Per Rismyhr; Laura Rophkof; Debi  Rudman; Joan Stallard; Kim Stanley; Suzanne of Doggletales; Sara Szauerzopf Kim Tarrington; Kim Vavolo; Judith Webb; Brent Wetnicka; Linda Zielinski

 

Cocker College Auction / Olga Evelyn ($23,035)

Special thanks to Stephanie Kaul and Karen Bruno Osper
Auction Item Donors: Gun Dog Supply/Affordable Kangaroo Leads; Gun Dog Supply; Bettie Campbell; Catherine Carey; Karen Cook; Joanna De Assis; Stacy Dobmeier; Tom Dowell; Deb Eastham; Patricia Elkins; Olga Evelyn; Jim Fehring; Andrea Floyd; Lisa Gaetner; Christye Groh; Kim Hampton; Laura Heidrich; Stephanie Kaul; Yelena Kuznetsova; Kelly Ladouceur; Lynda Lamensdorf; Debra Lampert-Rudman; Jessica Legath; Jackie Makoujy; Denise Mangold; David Margloin; Victoria Masterson; Kathleen Patterson; Bonnie Pike; Linda Pitts; Karen Osper; Olive Simmons; Suzanne Smith; Joann Stamm; Emily Staso; Nicole Techranchi; Rob & Teresa Tuccio; Kim Vavolo; Neville Ward; Judith Webb.

 

Show Prepration and trimming - The How...and the Why!/Linda Pitts ($5,095)

Special thanks to Elena Duggan, Laurie Foley, Marlene Ness, Quinn Ruvacava, and Jane Williams

Kenchii Scissor Raffle/Patricia Elkins   ($1,280.62)

Calendar Sales / Lisa Geartner ($250)

Christmas Photos at SNJCSC / Jackie Curry ($220)

Boutique Sales ($994.25)

 

The American Spaniel Club Foundation is excited to announce that it has raised over $88,000 for "Eye Support Cockers" - representing more than half of the funds needed for the project. Highlighting this extraordinary effort have been fundraisers headed up by (top left to right) ASC members Patricia Elkins (Kinsche scissor fund-raiser), Linda Pitts (represented by Stephanie Kaul for Show Grooming - the HOW and the WHY! presented at at the St. Louis National), Olga Evelyn (Cocker College Online Auction), and (seated left to right) Marlene Ness (CT Westchester Cocker Spaniel Club online auction presented during the Fall of 2013), and Kelly Ladouceur (American Cocker Network Stud Ad fundraiser). ASCF President Julie Virosteck accepted the checks on behalf of "Eye Support Cockers".

Breaking News

American Spaniel Club Foundation Committed to Fully Fund University of Pennsylvania Cocker Spaniel Cataract Research

Foundation will work together with American Spaniel Club, Inc. Board of Directors and members to generate the funding commitment.

After the a report from Doug McFarlane (Director/Scientific Research Chair) during the April Board meeting of the American Spaniel Club Foundation (ASCF), the Board in attendance unanimously committed to fully fund research on Cocker Spaniel cataracts proposed by Dr. Gustavo Aguirre of the University of Pennsylvania.

As requested by Dr. Aguirre, next step is ASCF will work with University administrators to finalize a contract formalizing a 3 year ASCF commitment to his research lab at the University at an estimated total cost of nearly $163,000. Most of the money will go to funding the staff required for this type of research. After a symbolic personal financial commitment by each ASCF Board member in attendance to the research, the ASCF Board simultaneously approved launching a rigorous fund raising effort that will be co-chaired by Laurie Foley and Elena Duggan, two ASC members who are experienced in large scale fund raising work.

Following this commitment, ASC President Calvin Ward and the ASC Board echoed support to ASCF for funding this research with a unanimous vote of support by those in attendance. ASC and ASCF working together with our membership and fanciers around the globe gives confidence that we can successfully fund this exciting research.

For those not familiar with the research proposed by Dr. Aguirre or who had some questions, here is a bit of background. The purpose of Dr. Aguirre’s research is to identify the gene and mutation responsible for inherited cataracts in Cocker Spaniels, and subsequently, to develop a genetic test that can identify genetically normal, affected, and carrier dogs. The mode of inheritance for this condition for many years now has been characterized as autosomal recessive meaning that affected dogs have inherited the mutant gene from both parents. This forms the basis for the research that will be conducted by Dr. Gustavo Aguirre’s laboratory at the University of Pennsylvania.

Cocker Spaniels like many breeds have a spectrum of clinical characteristics which affect dogs at various ages. The focus of this research is to identify the gene/mutation for the most common form of cataracts, one occurring in the 4-10 year age range. There seems to be somewhat limited data on the rate of occurrence for this condition in Cocker Spaniels, as no one organization has concentrated on collecting survey data in recent years.

Anecdotally, we all either have had cataracts in our Cocker lines or know someone who has had cataracts in their breeding stock. In ASCF discussions with Dr. Aguirre he cited a study based on CERF data from 2000-2008 that suggested cataracts were diagnosed in 7.3% of all Cocker Spaniels examined in those years. Dr. Aguirre feels this number is somewhat suspect since it includes both acquired and inherited cataracts and the latter category might include different genetic causes. Nonetheless, as Dr. Aguirre pointed out, the consequence of even a lower number is cause for great concern. For example, if we assume that say 5% is a more accurate number that translates into approximately 30% of all Cockers examined would be carriers of this condition.

Many ASC members are probably aware that Dr. Aguirre, with help from Deb Rudman and many other dedicated breeders in the northeast, has started collecting DNA along with his clinical exams to get an initial set of data to begin the research work. There has been some concern expressed that the collections are regionally limited. This is due only to current limited staffing and as Dr. Aguirre assured us. Once the contract with ASCF is finished and funding is provided, Dr. Aguirre can begin to hire the dedicated personnel that will facilitate broadening the collection process and support the work of the study at the University of Pennsylvania. In the meantime while the ASCF finishes the contract, we will launch our fundraising work to accelerate what has already been ably collected by ASC members. Further communications will be coming in that regard from our co-chairs.

Thank you to the ASC members who brought this research to ASCF attention and urged us to consider funding it. We look forward to working with the fancy in helping ASCF meet this financial commitment for the betterment of our breed. While success is never guaranteed in research, this is an excellent opportunity to potentially make a big difference for our breed.

Charles Born, Communications Director for American Spaniel Club Foundation

 

Attention Florida breeders and pet owners! University of Florida seeks participants in this AKC/CHF Grant:

Identifying What Attracts Ticks to Dogs

04/17/2013

Breed(s): Beagle, Cocker Spaniel, English Springer Spaniel, Greyhound, Labrador Retriever

Disease(s): Ticks

Study Type: Tissue Sample

Study Location: University of Florida

If you own a Beagle, Greyhound, Cocker Spaniel, Springer Spaniel, or Labrador Retriever, the University of Florida's Entomology Department is looking for you and your canine’s participation for a new research study funded by the AKC Canine Health Foundation.

The goal of this study is to identify chemicals from within your dog’s odor that are tick attractants and that could be used for various tick control methods in the future.

With your help, we will be able to collect chemical compounds that your dog excretes through its breath, hair, and skin secretions, that are potential attractants for the Brown Dog Tick.

Your participation would be limited to a one-time, 3 hour visit in your own home.

Sampling techniques are non-invasive and chemical-free.

Contact Information:

Corie Singer
Email: 
corie409@ufl.edu
Phone:(239) 340-8918

Follow the link to learn more about the disease and read the grant description

http://www.akcchf.org/research/funded-research/1780.html