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Genome-wide linkage study of atopic dermatitis in West Highland White Terriers.

Salzmann CA, Olivry TJ, Nielsen DM, Paps JS, Harris TL, Olby NJ - BMC Genet. (2011)

Bottom Line: The study was unable to detect any chromosomal regions significantly linked to canine AD.This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage.A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.

View Article: PubMed Central - HTML - PubMed

Affiliation: College of Veterinary Medicine, Department of Genetics, North Carolina State University, Raleigh, NC 27606, USA.

ABSTRACT

Background: Canine atopic dermatitis (AD) is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT). In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. The disorder shares many of the clinical and histopathological characteristics of human AD and represents an animal model of this disorder that could be used to further elucidate genetic causes of human AD. Microsatellite markers genotyped in families of WHWTs affected with AD were used to perform a genome-wide linkage study in order to isolate chromosomal regions associated with the disorder.

Results: Blood samples and health questionnaires were collected from 108 WHWTs spanning three families. A linkage simulation using these 108 dogs showed high power to detect a highly penetrant mutation. Ninety WHWTs were genotyped using markers from the Minimal Screening Set 2 (MSS-2). Two hundred and fifty six markers were informative and were used for linkage analysis. Using a LOD score of 2.7 as a significance threshold, no chromosomal regions were identified with significant linkage to AD. LOD scores greater than 1.0 were located in a 56 cM region of chromosome 7.

Conclusions: The study was unable to detect any chromosomal regions significantly linked to canine AD. This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage. A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.

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Power of trait detection. Simulations to determine the power to detect a highly penetrant mutation (A) and a mutation of low penetrance (B). The bold horizontal line indicates a LOD score of 2.7, bottom bar between the triangles signifies a mutation segregating with AD and the triangles represent locations of microsatellite markers.
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Figure 1: Power of trait detection. Simulations to determine the power to detect a highly penetrant mutation (A) and a mutation of low penetrance (B). The bold horizontal line indicates a LOD score of 2.7, bottom bar between the triangles signifies a mutation segregating with AD and the triangles represent locations of microsatellite markers.

Mentions: In the simulations for which a highly penetrant gene was generated, a LOD score equal to or greater than 2.7 was detected in 100% of the simulation runs, with a maximum score of 7.5 (Figure 1A). For a gene with low penetrance, none (0%) of the simulation runs resulted in a LOD score equal or greater than 2.7, the maximum being 2.6 (Figure 1B).


Genome-wide linkage study of atopic dermatitis in West Highland White Terriers.

Salzmann CA, Olivry TJ, Nielsen DM, Paps JS, Harris TL, Olby NJ - BMC Genet. (2011)

Power of trait detection. Simulations to determine the power to detect a highly penetrant mutation (A) and a mutation of low penetrance (B). The bold horizontal line indicates a LOD score of 2.7, bottom bar between the triangles signifies a mutation segregating with AD and the triangles represent locations of microsatellite markers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111396&req=5

Figure 1: Power of trait detection. Simulations to determine the power to detect a highly penetrant mutation (A) and a mutation of low penetrance (B). The bold horizontal line indicates a LOD score of 2.7, bottom bar between the triangles signifies a mutation segregating with AD and the triangles represent locations of microsatellite markers.
Mentions: In the simulations for which a highly penetrant gene was generated, a LOD score equal to or greater than 2.7 was detected in 100% of the simulation runs, with a maximum score of 7.5 (Figure 1A). For a gene with low penetrance, none (0%) of the simulation runs resulted in a LOD score equal or greater than 2.7, the maximum being 2.6 (Figure 1B).

Bottom Line: The study was unable to detect any chromosomal regions significantly linked to canine AD.This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage.A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.

View Article: PubMed Central - HTML - PubMed

Affiliation: College of Veterinary Medicine, Department of Genetics, North Carolina State University, Raleigh, NC 27606, USA.

ABSTRACT

Background: Canine atopic dermatitis (AD) is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT). In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. The disorder shares many of the clinical and histopathological characteristics of human AD and represents an animal model of this disorder that could be used to further elucidate genetic causes of human AD. Microsatellite markers genotyped in families of WHWTs affected with AD were used to perform a genome-wide linkage study in order to isolate chromosomal regions associated with the disorder.

Results: Blood samples and health questionnaires were collected from 108 WHWTs spanning three families. A linkage simulation using these 108 dogs showed high power to detect a highly penetrant mutation. Ninety WHWTs were genotyped using markers from the Minimal Screening Set 2 (MSS-2). Two hundred and fifty six markers were informative and were used for linkage analysis. Using a LOD score of 2.7 as a significance threshold, no chromosomal regions were identified with significant linkage to AD. LOD scores greater than 1.0 were located in a 56 cM region of chromosome 7.

Conclusions: The study was unable to detect any chromosomal regions significantly linked to canine AD. This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage. A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.

Show MeSH
Related in: MedlinePlus