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Candidate genes for idiopathic epilepsy in four dog breeds.

Ekenstedt KJ, Patterson EE, Minor KM, Mickelson JR - BMC Genet. (2011)

Bottom Line: Idiopathic epilepsy (IE) is a naturally occurring and significant seizure disorder affecting all dog breeds.Because dog breeds are genetically isolated populations, it is possible that IE is attributable to common founders and is genetically homogenous within breeds.Most of these candidate genes were not significantly associated with IE in these four dog breeds, while a few genes remained inconclusive.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, 1352 Boyd Avenue, Saint Paul, Minnesota 55108, USA. eken0003@umn.edu

ABSTRACT

Background: Idiopathic epilepsy (IE) is a naturally occurring and significant seizure disorder affecting all dog breeds. Because dog breeds are genetically isolated populations, it is possible that IE is attributable to common founders and is genetically homogenous within breeds. In humans, a number of mutations, the majority of which are genes encoding ion channels, neurotransmitters, or their regulatory subunits, have been discovered to cause rare, specific types of IE. It was hypothesized that there are simple genetic bases for IE in some purebred dog breeds, specifically in Vizslas, English Springer Spaniels (ESS), Greater Swiss Mountain Dogs (GSMD), and Beagles, and that the gene(s) responsible may, in some cases, be the same as those already discovered in humans.

Results: Candidate genes known to be involved in human epilepsy, along with selected additional genes in the same gene families that are involved in murine epilepsy or are expressed in neural tissue, were examined in populations of affected and unaffected dogs. Microsatellite markers in close proximity to each candidate gene were genotyped and subjected to two-point linkage in Vizslas, and association analysis in ESS, GSMD and Beagles.

Conclusions: Most of these candidate genes were not significantly associated with IE in these four dog breeds, while a few genes remained inconclusive. Other genes not included in this study may still be causing monogenic IE in these breeds or, like many cases of human IE, the disease in dogs may be likewise polygenic.

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Vizsla linkage family 1 pedigree. Pedigree of Vizsla family 1. Squares and circles represent males and females, respectively. Filled shapes represent cases; those with question marks represent unknown phenotype status. Dogs with arrows were genotyped in this study. The dog marked with an arrow and a + is included on both families 1 & 2, effectively making this one very large family. The Vizsla pedigrees were broken into ten smaller families to decrease inbreeding loops before being analyzed in linkage analysis. Three dogs representing one of the ten sub-families are not shown on either pedigree.
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Figure 1: Vizsla linkage family 1 pedigree. Pedigree of Vizsla family 1. Squares and circles represent males and females, respectively. Filled shapes represent cases; those with question marks represent unknown phenotype status. Dogs with arrows were genotyped in this study. The dog marked with an arrow and a + is included on both families 1 & 2, effectively making this one very large family. The Vizsla pedigrees were broken into ten smaller families to decrease inbreeding loops before being analyzed in linkage analysis. Three dogs representing one of the ten sub-families are not shown on either pedigree.

Mentions: For Vizslas, the depth of the available DNA samples from multiple siblings, parents, and many grandparents allowed the development of multi-generation pedigrees (Figure 1 and Figure 2) suitable for genetic linkage analysis. 96 dogs were included: 31 affected dogs, 60 unaffected dogs, and 5 dogs with unknown phenotype status. These dogs were separated into two large family pedigrees shown in Figures 1 and 2, and were subsequently broken into ten smaller families to decrease inbreeding loops for linkage analysis and calculation of LOD scores.


Candidate genes for idiopathic epilepsy in four dog breeds.

Ekenstedt KJ, Patterson EE, Minor KM, Mickelson JR - BMC Genet. (2011)

Vizsla linkage family 1 pedigree. Pedigree of Vizsla family 1. Squares and circles represent males and females, respectively. Filled shapes represent cases; those with question marks represent unknown phenotype status. Dogs with arrows were genotyped in this study. The dog marked with an arrow and a + is included on both families 1 & 2, effectively making this one very large family. The Vizsla pedigrees were broken into ten smaller families to decrease inbreeding loops before being analyzed in linkage analysis. Three dogs representing one of the ten sub-families are not shown on either pedigree.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111397&req=5

Figure 1: Vizsla linkage family 1 pedigree. Pedigree of Vizsla family 1. Squares and circles represent males and females, respectively. Filled shapes represent cases; those with question marks represent unknown phenotype status. Dogs with arrows were genotyped in this study. The dog marked with an arrow and a + is included on both families 1 & 2, effectively making this one very large family. The Vizsla pedigrees were broken into ten smaller families to decrease inbreeding loops before being analyzed in linkage analysis. Three dogs representing one of the ten sub-families are not shown on either pedigree.
Mentions: For Vizslas, the depth of the available DNA samples from multiple siblings, parents, and many grandparents allowed the development of multi-generation pedigrees (Figure 1 and Figure 2) suitable for genetic linkage analysis. 96 dogs were included: 31 affected dogs, 60 unaffected dogs, and 5 dogs with unknown phenotype status. These dogs were separated into two large family pedigrees shown in Figures 1 and 2, and were subsequently broken into ten smaller families to decrease inbreeding loops for linkage analysis and calculation of LOD scores.

Bottom Line: Idiopathic epilepsy (IE) is a naturally occurring and significant seizure disorder affecting all dog breeds.Because dog breeds are genetically isolated populations, it is possible that IE is attributable to common founders and is genetically homogenous within breeds.Most of these candidate genes were not significantly associated with IE in these four dog breeds, while a few genes remained inconclusive.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, 1352 Boyd Avenue, Saint Paul, Minnesota 55108, USA. eken0003@umn.edu

ABSTRACT

Background: Idiopathic epilepsy (IE) is a naturally occurring and significant seizure disorder affecting all dog breeds. Because dog breeds are genetically isolated populations, it is possible that IE is attributable to common founders and is genetically homogenous within breeds. In humans, a number of mutations, the majority of which are genes encoding ion channels, neurotransmitters, or their regulatory subunits, have been discovered to cause rare, specific types of IE. It was hypothesized that there are simple genetic bases for IE in some purebred dog breeds, specifically in Vizslas, English Springer Spaniels (ESS), Greater Swiss Mountain Dogs (GSMD), and Beagles, and that the gene(s) responsible may, in some cases, be the same as those already discovered in humans.

Results: Candidate genes known to be involved in human epilepsy, along with selected additional genes in the same gene families that are involved in murine epilepsy or are expressed in neural tissue, were examined in populations of affected and unaffected dogs. Microsatellite markers in close proximity to each candidate gene were genotyped and subjected to two-point linkage in Vizslas, and association analysis in ESS, GSMD and Beagles.

Conclusions: Most of these candidate genes were not significantly associated with IE in these four dog breeds, while a few genes remained inconclusive. Other genes not included in this study may still be causing monogenic IE in these breeds or, like many cases of human IE, the disease in dogs may be likewise polygenic.

Show MeSH
Related in: MedlinePlus