Linkage Analysis Of Microsatellite DNA Marker In Familial Simple Febrile Seizures

Objective: Febrile seizures (FS, also called Febrile convulsions, FC) are the most common form of convulsions in childhood, which occur in 2-5% of children between six months and five years of age. Twin and family studies have shown important genetic components in FS. Autosomal dominant (AD), autosomal recessive (AR), and polygenic inheritance have been described. Up to now, six genetic loci responsible for FS have been mapped: FEB1 on chromosome 8q13–q21, FEB2 on 19p13.3, FEB3 on 2q23–q24, FEB4 on 5q14–q15, FEB5 on 6q22-q24 and a locus on 18p11.2. However, the specific gene responsible for FS has not been identified and this disease has conspicuous genetic heterogeneity. The research is to localize the genetic loci of FS.Material and Method:In this research, we collected a FS pedigree from XunYang Country, AnKang City, ShaanXi Province, China, in which all the FS patients have the FS clinical characteristic without other seizures disease. We conducted linkage analysis for the pedigree with IBD and mapped on the locus chromosome 15q21.4-q23. Then three STR markers(D15S818,D15S1507 and GATA153F11) were selected on this locus. The linkage analysis has been done with GeneHunter soft and Fastlink soft. Then we selected nine STR marker(D15S1016,D15S117,D15S643,D15S155,D15S1036,D15S974,D15S987,D15S983,D15S984) on the new locus. The linkage analysis has been done with GeneHunter soft and Linkage soft for all the twelve STR markers. 50 normal controls were parallelly analyzed to prove that the twelve STR mareker genotypes were in Hardy-Weinberg equilibrium.Results: When the penetrance is maximal, the multi-point linkage analysis shows that the Maximal LOD score is between D15S1507 and GATA153F11(1.29) using GeneHunter soft. The maximum two-point LOD score is 1.54 at GATA153F11. Added nine STR markers on the new locus, when the penetrance is 65%, the multi-point linkage result shows the maximal LOD score is between D15S1036 and D15S1507(0.77) using the GeneHunter soft. The maximum two-point LOD score is 1.21 at D15S1036 using the LINKAGE soft.Conclusion: The two-point Lod score are both >1 at D15S1507 and GATA153F11 and the multi-point Lod score is 1.29 between D15S1507 and GATA153F11. The result showed that the linkage may not exist between D15S818 and D15S1507 but between D15S1507 and GATA153F11. After added the other nine STR markers, when the penetrance is 65%,the multi-point linkage result shows that the maximal LOD score is between D15S1036 and D15S1507(0.77) using the GeneHunter soft. The maximum two-point LOD score is 1.21 at D15S1036 using the LINKAGE soft. The results shows that we could not certain the possibility that the linkage exists between Febrile Seizures and the STR markers D15S1036 and D15S1507. The candidate genes may be existis between the STR markers D15S1036 and D15S1507 and may be close to D15S1036.