Genome-wide association studies for multiple diseases of the German Shepherd Dog

Tsai, Kate L.; Noorai, Rooksana E.; Starr-Moss, Alison N.; Quignon, Pascale; Rinz, Caitlin J.; Ostrander, Elaine A.; Steiner, Jörg M.; Murphy, Keith E.; Clark, Leigh Anne

doi:10.1007/s00335-011-9376-9

Cited by 20 publications

(27 citation statements)

References 46 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, if we treat these littermates as single animals, the revised total of nine GSDs with acromegaly still suggests this breed is overrepresented and further genetic studies of this potential predisposition are merited (Tsai et al, 2012). The clinical signs we report are similar to those documented previously (Eigenmann and Venker-van Haagen, 1981;Eigenmann et al, 1983Eigenmann et al, , 1984Selman et al, 1991;Jensen et al, 1993;Villforth, 1998;Norman et al, 2006).…”

Section: Discussionsupporting

confidence: 77%

Spontaneous acromegaly: A retrospective case control study in German shepherd dogs

Fracassi

Zagnoli

Rosenberg

et al. 2014

The Veterinary Journal

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 77%

Spontaneous acromegaly: A retrospective case control study in German shepherd dogs

Fracassi

Zagnoli

Rosenberg

et al. 2014

The Veterinary Journal

View full text Add to dashboard Cite

“…In addition, there are many other studies of GWAS in other model organisms that are similar to our study, including studies in mice (Payseur and Place 2007), Arabidopsis (Zhao et al 2007), maize and rice (Brachi et al 2011), tomato (Ranc et al 2012), dog (Tsai et al 2012), and Drosophila melanogaster (Mackay et al 2012). Recent admixture is a pervasive phenomenon in many species.…”

Section: Discussionsupporting

confidence: 71%

“…Recent breakthroughs in genotyping and sequencing technologies have facilitated an explosion of genome-wide association studies (GWAS) resulting in the discovery of many new associations of SNPs with complex traits, especially in humans (Hindorff et al 2009). GWAS is also an increasingly important mapping approach in other nonhuman species, including plant species such as maize, rice, and Arabidopsis (reviewed in Brachi et al 2011), mouse (Payseur and Place 2007), Drosophila (Mackay et al 2012), and dog (Tsai et al 2012). However, the feasibility of GWAS in Saccharomyces cerevisiae, an important model organism and agricultural species, has not yet been fully studied.…”

mentioning

confidence: 99%

Local Ancestry Corrects for Population Structure in Saccharomyces cerevisiae Genome-Wide Association Studies

Diao

Chen

2012

Genetics

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) have become an important method for mapping the genetic loci underlying complex phenotypic traits in many species. A crucial issue when performing GWAS is to control for the underlying population structure because not doing so can lead to spurious associations. Population structure is a particularly important issue in nonhuman species since it is often difficult to control for population structure during the study design phase, requiring population structure to be corrected statistically after the data have been collected. It has not yet been established if GWAS is a feasible approach in Saccharomyces cerevisiae, an important model organism and agricultural species. We thus performed an empirical study of statistical methods for controlling for population structure in GWAS using a set of 201 phenotypic traits measured in multiple resequenced strains of S. cerevisiae. We complemented our analysis of real data with an extensive set of simulations. Our main result is that a mixed linear model using the local ancestry of the strain as a covariate is effective at controlling for population structure, consistent with the mosaic structure of many S. cerevisiae strains. We further studied the evolutionary forces acting on the GWAS SNPs and found that SNPs associated with variation in phenotypic traits are enriched for low minor allele frequencies, consistent with the action of negative selection on these SNPs. Despite the effectiveness of local ancestry correction, GWAS remains challenging in highly structured populations, such as S. cerevisiae. Nonetheless, we found that, even after correcting for population structure, there is still sufficient statistical power to recover biologically meaningful associations.

show abstract

“…Genetic disease susceptibility studies in dog breeds are especially powerful, owing to dogs’ relative inbreeding and the attendant lack of genetic heterogeneity [33,34]. This power is supported by recent genetic susceptibility studies in Bernese mountain dogs and German shepherds [35,36], as well as preliminary array-CGH based studies in canine lymphoma [18]. Golden retrievers represent a breed at especially high risk of developing lymphoma in which heritability is strongly implied [20].…”

Section: Discussionmentioning

confidence: 99%

DNA Repair Deficiency as a Susceptibility Marker for Spontaneous Lymphoma in Golden Retriever Dogs: A Case-Control Study

et al. 2013

View full text Add to dashboard Cite

There is accumulating evidence that an individual’s inability to accurately repair DNA damage in a timely fashion may in part dictate a predisposition to cancer. Dogs spontaneously develop lymphoproliferative diseases such as lymphoma, with the golden retriever (GR) breed being at especially high risk. Mechanisms underlying such breed susceptibility are largely unknown; however, studies of heritable cancer predisposition in dogs may be much more straightforward than similar studies in humans, owing to a high degree of inbreeding and more limited genetic heterogeneity. Here, we conducted a pilot study with 21 GR with lymphoma, 20 age-matched healthy GR and 20 age-matched healthy mixed-breed dogs (MBD) to evaluate DNA repair capability following exposure to either ionizing radiation (IR) or the chemical mutagen bleomycin. Inter-individual variation in DNA repair capacity was evaluated in stimulated canine lymphoctyes exposed in vitro utilizing the G2 chromosomal radiosensitivity assay to quantify clastogen-induced chromatid-type aberrations (gaps and breaks). Golden retrievers with lymphoma demonstrated elevated sensitivity to induction of chromosome damage following either challenge compared to either healthy GR or MBD at multiple doses and time points. Using the 75th percentile of chromatid breaks per 1,000 chromosomes in the MBD population at 4 hours post 1.0 Gy IR exposure as a benchmark to compare cases and controls, GR with lymphoma were more likely than healthy GR to be classified as “sensitive” (odds ratio = 21.2, 95% confidence interval 2.3-195.8). Furthermore, our preliminary findings imply individual (rather than breed) susceptibility, and suggest that deficiencies in heritable factors related to DNA repair capabilities may be involved in the development of canine lymphoma. These studies set the stage for larger confirmatory studies, as well as candidate-based approaches to probe specific genetic susceptibility factors.

show abstract

Genome-wide association studies for multiple diseases of the German Shepherd Dog

Cited by 20 publications

References 46 publications

Spontaneous acromegaly: A retrospective case control study in German shepherd dogs

Spontaneous acromegaly: A retrospective case control study in German shepherd dogs

Local Ancestry Corrects for Population Structure in Saccharomyces cerevisiae Genome-Wide Association Studies

DNA Repair Deficiency as a Susceptibility Marker for Spontaneous Lymphoma in Golden Retriever Dogs: A Case-Control Study

Contact Info

Product

Resources

About