However, the extent of inbreeding within specific dog breeds has allowed the identification of certain animals that are at particularly high risk of seizure development. No fewer than 26 dog breeds have shown at least some evidence of heritable epilepsies.
2Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 295 AS/VM, 1988 Fitch Avenue, St. Paul, Minnesota, 55108, USAFind articles by
It is possible that canine IE, like the majority of human IE, is a genetically complex disease in most breeds and that multiple loci contribute to susceptibility in any given breed. The present study would very likely have detected a major contributing locus, and it is unlikely that a truly causative locus is being excluded as a false negative. In humans, the vast majority of IE remains genetically unexplained and is considered to be polygenic [37-39]. A recent study by Oberbauer et al.  utilized microsatellites in a genome-wide linkage scan for epilepsy loci in the Belgian shepherd dog and concluded that the disease was highly polygenic, reporting a tentative six QTLs. These results further support the conclusion that canine IE is a more complex disease than originally hypothesized. Whole-genome association analyses with SNP arrays are likely the platform of choice for further studies of IE, as they can query tens of thousands of markers simultaneously across the genome and are better able to identify multiple susceptibility loci. Additionally, copy number variants (CNVs) have been increasingly shown to be involved in neurologic disorders such as autism [41,42] and schizophrenia [43,44], as well as epilepsy . CNV studies of canine epilepsy may reveal this as a similar mechanism for disease in both species.
Cohorts of affected and unaffected dogs for genotyping were assembled for each of the four test breeds – the Vizsla, the GSMD, the ESS, and the Beagle. Ultimately, the available samples determined what type of genetic analysis was conducted for each breed.
The aim of the present study was to take advantage of the likely founder effect occurring in purebred dogs with IE in order to investigate an underlying genetic basis for IE in four dog breeds: the Vizsla, the English Springer Spaniel (ESS), the Greater Swiss Mountain Dog (GSMD) and the Beagle. A candidate gene approach was utilized; genes known to be involved in inherited human epilepsy, along with two genes involved in mouse epilepsy models and additional related gene family members, were selected. Most candidate genes tested were ion channels. Microsatellite markers within or very close to these genes were used to generate genotypes which were then subjected to either two-point linkage analysis or association chi-square studies. Using four different breeds, which may each have different forms of IE, increased the chances of potentially finding an associated gene in at least one of the breeds.
For the GSMD, discordant full-sibling or half-sibling pairs of affected (n = 24) and unaffected (n = 24) dogs were assembled and used in association studies. Siblings were used to help avoid spurious association from population stratification. In a few instances, two different pairs of siblings were related to each other, such as sharing one parent.
Natural Occurrenceof Inbreeding
This is not to say that inbreeding does not occur naturally. A wolf pack, which is isolated from other wolf packs, by geographical or other factors, can become very inbred. The effect of any deleterious genes becomes noticeable in later generations as the majority of the offspring inherit these genes. Scientists have discovered that wolves, even if living in different areas, are genetically very similar. Possibly the desolation of their natural habitat has drastically reduced wolf numbers in the past, creating a genetic bottleneck.
In the wolf, the lack of genetic diversity makes them susceptible to disease since they lack the ability to resist certain viruses. Extreme inbreeding affects their reproductive success with small litter sizes and high mortality rates. Some scientists hope that they can develop a more varied gene pool by introducing wolves from other areas into the inbred wolf packs.
Another animal suffering from the effects of inbreeding is the giant panda. As with the wolf, this has led to poor fertility among pandas and high infant mortality rates. As panda populations become more isolated from one another (due to humans blocking the routes which pandas once used to move from one area to another), pandas have greater difficulty in finding a mate with a different mix of genes and breed less successfully.
In cats natural isolation and inbreeding have given rise to domestic breeds such as the Manx which developed on an island so that the gene for taillessness became widespread despite the problems associated with it. Apart from the odd cat jumping ship on the Isle of Man, there was little outcrossing and the effect of inbreeding is reflected in smaller-than-average litter sizes (geneticists believe that more Manx kittens than previously thought are reabsorbed due to genetic abnormality), stillbirths and spinal abnormalities which diligent breeders have worked so hard to eliminate.
Some feral colonies become highly inbred due to being isolated from other cats (e.g. on a remote farm) or because other potential mates in the area have been neutered, removing them from the gene pool. Most cat workers dealing with ferals have encountered some of the effects of inbreeding. Within such colonies there may be a higher than average occurrence of certain traits. Some are not serious, e.g. a predominance of calico pattern cats. Other inherited traits which can be found in greater than average numbers in inbred colonies include polydactyly (the most extreme case reported so far being an American cat with nine toes on each foot), dwarfism (although dwarf female cats can have problems when trying to deliver kittens due to the kittens head size), other structural deformities or a predisposition to certain inheritable conditions.
The ultimate result of continued inbreeding is terminal lack of vigor and probable extinction as the gene pool contracts, fertility decreases, abnormalities increase and mortality rates rise.
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