This study will identify the loci involved in the expression of idiopathic generalized epilepsy (IGE) and investigate their interactions. In the previous grant period, we: 1) Completed a genome scan for loci of IGE; 2) Discovered at least 4 locations of genes for IGE; 3) Demonstrated and partly resolved heterogeneity in Juvenile Myoclonic Epilepsy (JME); 4) Narrowed the number of candidate loci for EJM1 to seven; 5) Found evidence that JME may be different in Caucasians and non-Caucasians. Pursuing these findings, we have the following aims: 1. Ascertain families with adolescent-onset forms of IGE. 2. Test for linkage heterogeneity at the loci on chromosomes 5, 8, and 18. 3. Test for further evidence of linkage at loci with promising but less significant lod scores on chromosomes 6q and 1. 4. Determine the relationship between genotype and seizure expression, correlating the linkage signal with the seizure types in the families. 5. Test whether non-EJM1 forms of JME map to chromosome 6q. 6. Test whether the frequency of JME due to EJM1 in non-Caucasians is the same as in Caucasians. 7. Determine which of 7 candidate loci is EJM1. 8. Fine-mapping on the candidate regions on chromosomes 5, 8, and 18. The exciting previous results suggest we may now have located many of the genes for adolescent-onset IGE. We will use the linkage and population studies to determine how interactions between the loci influence seizure type and, by eventually determining the actual disease loci, delineate how these loci produce seizures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027941-16
Application #
6743099
Study Section
Special Emphasis Panel (ZNS1-SRB-W (01))
Program Officer
Fureman, Brandy E
Project Start
1990-01-01
Project End
2006-07-31
Budget Start
2004-05-01
Budget End
2006-07-31
Support Year
16
Fiscal Year
2004
Total Cost
$1,031,921
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Pathak, Shilpa; Miller, James; Morris, Emily C et al. (2018) DNA methylation of the BRD2 promoter is associated with juvenile myoclonic epilepsy in Caucasians. Epilepsia 59:1011-1019
Subaran, Ryan L; Conte, Juliette M; Stewart, William C L et al. (2015) Pathogenic EFHC1 mutations are tolerated in healthy individuals dependent on reported ancestry. Epilepsia 56:188-94
Lipner, Ettie M; Tomer, Yaron; Noble, Janelle A et al. (2015) Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA. J Diabetes Res 2015:694107
Corso, Barbara; Greenberg, David A (2014) Using linkage analysis to detect gene-gene interaction by stratifying family data on known disease, or disease-associated, alleles. PLoS One 9:e93398
Chachua, T; Goletiani, C; Maglakelidze, G et al. (2014) Sex-specific behavioral traits in the Brd2 mouse model of juvenile myoclonic epilepsy. Genes Brain Behav 13:702-12
Tomer, Yaron; Hasham, Alia; Davies, Terry F et al. (2013) Fine mapping of loci linked to autoimmune thyroid disease identifies novel susceptibility genes. J Clin Endocrinol Metab 98:E144-52
Lipner, E M; Tomer, Y; Noble, J A et al. (2013) HLA class I and II alleles are associated with microvascular complications of type 1 diabetes. Hum Immunol 74:538-44
Greenberg, David A; Stewart, William C L (2012) How should we be searching for genes for common epilepsy? A critique and a prescription. Epilepsia 53 Suppl 4:72-80
Strug, Lisa J; Addis, Laura; Chiang, Theodore et al. (2012) The genetics of reading disability in an often excluded sample: novel loci suggested for reading disability in Rolandic epilepsy. PLoS One 7:e40696
Greenberg, David A (2011) Computer simulation is an undervalued tool for genetic analysis: a historical view and presentation of SHIMSHON--a Web-based genetic simulation package. Hum Hered 72:247-57

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