| First Author | Tyler AL | Year | 2014 |
| Journal | Genes Brain Behav | Volume | 13 |
| Issue | 8 | Pages | 831-40 |
| PubMed ID | 25251056 | Mgi Jnum | J:226727 |
| Mgi Id | MGI:5698327 | Doi | 10.1111/gbb.12178 |
| Citation | Tyler AL, et al. (2014) A genetic interaction network model of a complex neurological disease. Genes Brain Behav 13(8):831-40 |
| abstractText | Absence epilepsy (AE) is a complex, heritable disease characterized by a brief disruption of normal behavior and accompanying spike-wave discharges (SWD) on the electroencephalogram. Only a handful of genes has been definitively associated with AE in humans and rodent models. Most studies suggest that genetic interactions play a large role in the etiology and severity of AE, but mapping and understanding their architecture remains a challenge, requiring new computational approaches. Here we use combined analysis of pleiotropy and epistasis (CAPE) to detect and interpret genetic interactions in a meta-population derived from three C3H x B6J strain crosses, each of which is fixed for a different SWD-causing mutation. Although each mutation causes SWD through a different molecular mechanism, the phenotypes caused by each mutation are exacerbated on the C3H genetic background compared with B6J, suggesting common modifiers. By combining information across two phenotypic measures - SWD duration and frequency - CAPE showed a large, directed genetic network consisting of suppressive and enhancing interactions between loci on 10 chromosomes. These results illustrate the power of CAPE in identifying novel modifier loci and interactions in a complex neurological disease, toward a more comprehensive view of its underlying genetic architecture. |
